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The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Most vibration-based energy harvesters, including piezoelectric harvester system, perform efficiently at only its resonant frequency as linear resonators, usually at very high frequency which are out of the range of frequency of interest. In real life applications, these linear resonators are impractical since real ambient vibrations are simply having varying lower frequencies. Hence, design a tuneable vibration energy harvester at a lower and useful frequency range of interest are essential in allowing promising energy output to meet intended power input at a more practical approach. In this paper, the piezoelectric voltage energy harvester (PVEH) was designed with a flexible fixture with the aim to reduce its first fundamental natural frequency. Two thickness of elastic fixtures were applied to generate power on PVEH. Three experimental techniques were used to measure the vibration characteristics of PVEH. First, the full-field optical technique, amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI) measured simultaneously the resonant frequencies and mode shapes. This is followed by the pointwise measurement system, laser Doppler vibrometer (LDV) in which the resonant frequencies were measured by dynamic signal swept-sine analysis. The resonant frequencies and anti-resonant frequencies were also obtained by impedance analysis. The results obtained from experimental measurements were compared with finite element numerical calculation. It is found that the boundary conditions under the elastic fixtures can effectively reduce the resonant frequency of the PVEH with a reasonable voltage output. The fundamental natural frequency of PVEH with the thickness of 0.58-mm elastic fixture is reduced to 37 Hz maintaining at 7.1 volts (1.2 mW), in comparison with the natural frequency on cantilevered PVEH at 78 Hz that produces 7.7 volts (6.5 mW).
Propofol is a intravenous anaesthetic most commonly used in ultrasound oocyte retrieval. We studied if the use of propofol had an effect on mouse oocyte maturation, pregnancy, childbirth and progeny and investigated the correlation between propofol side effects and reproductive performance in mice. There was no statistical difference in mating, pregnancy, childbirth, litter size, the number of stillbirths and survival between each group (P>0.05). Propofol also had no effect on polar body extrusion in oocyte maturation as well as on pronucleus formation and, subsequently, early embryo development (P>0.05). An increased concentration of propofol had no effect on this result, although propofol at more than 0.01 mg/ml reduced polar body extrusion. Different concentrations of propofol had no effect on oocyte culture in vitro, pronucleus formation and early embryo development.
Recent evidence shows that excess nicotinamide can cause epigenetic changes in developing rats. The aim of the present study was to investigate the effects of maternal nicotinamide supplementation on the fetus. Female rats were randomised into four groups fed a standard chow diet (control group) or diets supplemented with 1 g/kg of nicotinamide (low-dose group), 4 g/kg of nicotinamide (high-dose group) or 4 g/kg of nicotinamide plus 2 g/kg of betaine (betaine group) for 14–16 d before mating and throughout the study. Fetal tissue samples were collected on the 20th day of pregnancy. Compared with the control group, the high-dose group had a higher fetal death rate, and the average fetal body weight was higher in the low-dose group but lower in the high-dose group. Nicotinamide supplementation led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamide N-methyltransferase, DNA methyltransferase 1, catalase and tumour protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic α-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. The present study raises the concern that maternal nicotinamide supplementation may play a role in the development of epigenetic-related diseases in the offspring.
Ecological evidence suggests that niacin (nicotinamide and nicotinic acid) fortification may be involved in the increased prevalence of obesity and type 2 diabetes, both of which are associated with insulin resistance and epigenetic changes. The purpose of the present study was to investigate nicotinamide-induced metabolic changes and their relationship with possible epigenetic changes. Male rats (5 weeks old) were fed with a basal diet (control group) or diets supplemented with 1 or 4 g/kg of nicotinamide for 8 weeks. Low-dose nicotinamide exposure increased weight gain, but high-dose one did not. The nicotinamide-treated rats had higher hepatic and renal levels of 8-hydroxy-2′-deoxyguanosine, a marker of DNA damage, and impaired glucose tolerance and insulin sensitivity when compared with the control rats. Nicotinamide supplementation increased the plasma levels of nicotinamide, N1-methylnicotinamide and choline and decreased the levels of betaine, which is associated with a decrease in global hepatic DNA methylation and uracil content in DNA. Nicotinamide had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions (nicotinamide N-methyltransferase and DNA methyltransferase 1), for homocysteine metabolism (betaine–homocysteine S-methyltransferase, methionine synthase and cystathionine β-synthase) and for oxidative defence (catalase and tumour protein p53). It is concluded that nicotinamide-induced oxidative tissue injury, insulin resistance and disturbed methyl metabolism can lead to epigenetic changes. The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.
Polyimide (PI)-matrix composite films containing inorganic nanoparticles (nano-Al2O3 and nano-TiO2) have been fabricated. A proposed model is used to explain different structures of the (Al2O3–TiO2)/PI (ATP) films synthesized by employing in situ polymerization. Dependences of dielectric permittivities of the ATP films on frequency and temperature were studied. Results show the breakdown strength of the films decreases with prolonging the corona aging time. The incorporation of the nano-Al2O3 and nano-TiO2 particles significantly improves the corona resistance of the films. The corona aging also influences the infrared absorbance, the glass transition temperature (Tg), and loss factor (tanδ) of the ATP films.
Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture.
We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the Annexin V-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA.
We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly.
Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.
To identify the disease-causing gene for a large multi-generational Chinese family affected by familial hypertrophic cardiomyopathy (FHCM), genome-wide screening was carried out in a Chinese family with FHCM using micro-satellite markers, and linkage analysis was performed using the MLINK program. The disease locus was mapped to 1q32 in this family. Screening for a mutation in the cardiac troponin T (cTnT) gene was performed by a PCR and sequencing was done with an ABI Prism 3700 sequencer. A novel C→G transition located in the ninth exon of the cTnT gene, leading to a predicted amino acid residue change from Ile to Met at codon 90, was identified in all individuals with hypertrophic cardiomyopathy (HCM). The results presented here strongly suggest that Ile90Met, a novel mutation in the cTnT gene, is causative agent of HCM in this family.
HbUEP, an ubiquitin extension protein gene from latex of the rubber tree (Hevea brasiliensis) was cloned and sequenced using a differentially ethphon-induced expressed cDNA subtraction library. The cDNA had 771 bp nucleotides, comprising a 226 bp 3′ untranslated region (UTR), 77 bp 5′UTR and a 468 bp open reading frame encoding a 156 amino acid peptide. Southern blotting analysis showed that this gene was a low copy number gene in the H. brasiliensis genome. Within 24 h after application of ethphon, the gene was expressed weakly in both control and latex sampled at 6 h, and strongly in latex sampled at 12 h, showing that this gene expression could be regulated by ethphon. Ethphon could increase the latex yield in H. brasiliensis. It is suggested that the HbUEP gene may be involved in the regulation of ethphon-induced high latex yield in H. brasiliensis.
Crystalline tungsten suboxide nanowires were grown on silicon substrates by thermal evaporation of tungsten powder in a flow of argon gas without any catalyst. With different growth temperatures, two kinds of tungsten suboxide nanowires (W18O49 and W20O58) were obtained. The structures, morphologies, and compositions of these two nanowires were characterized by scanning electron microscopy (SEM), electron probe microanalyzer (EPMA), x-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), x-ray photoelectron spectroscopy (XPS), and Raman techniques. The results show that XRD and TEM are not good characterization techniques for identifying W18O49 and W20O58 nanowires; however, Raman spectroscopy (RS) is a powerful tool to distinguish the difference between them. This is due to the notable molecular bond contributing to the vibrational frequency.
To investigate the influence of pulse repetition rate on the average
size of the nanoparticles, nanocrystalline Si films were prepared by
pulsed laser ablation in high-purity Ar gas with a pressure of 10 Pa at
room temperature, under the pulse repetition rates between 1 and 40 Hz,
using a nanosecond laser. Raman, X-ray diffraction spectra, and scanning
electron microscopy images show that with increasing pulse repetition
rate, the average size of the nanoparticles in the film first decreases
and reach its minimum at 20 Hz, and then increases, which may be
attributed to the nonlinear dynamics of the laser-ablative deposition. In
our experiment conditions, the duration of the ambient restoration, a
characteristic parameter being used to distinguish nonlinear or linear
region, is about a few seconds from the order of magnitude, which is
consistent with the previous experimental observation. More detailed model
to explain quantitively the observed effect is under investigation.
Interferon, an important cytokine, is an immunomodulator and possesses antiviral and anti-tumour activity. In vitro, it can be administrated in the treatment of diseases alone or with genetically engineered vaccine to enhance the immune effect of the latter. The recombinant transferring vector pSY681–ChIFN-γ was obtained in this study by inserting the chicken type II interferon (ChIFN-γ) gene into the Fowlpox virus (FPV) transferring vector pSY681. The resulting plasmid was then transfected into chicken embryo fibroblast (CEF) cell cultures pre-infected with the parental FPV S-FPV-017. Finally, the recombinant Fowlpox virus (rFPV) expressing ChIFN-γ (rFPV–ChIFN-γ) was produced by homologous recombination with the FPV gene in CEF. rFPV-positive plaques were verified by polymerase chain reaction (PCR), restriction analysis and indirect immunofluorescence assays. The rFPV–ChIFN-γ supernatants, cultured in CEF for 72 h and inoculated into rat fibroblasts (L929), had an inhibitory effect on the replication of Rous sarcoma virus (RSV) with an antiviral titre of 2048 U/ml.
Eleven isolates within four species of the entomogenous fungus Aschersonia from China, the USA, Japan, the Philippines, Malaysia and Columbia were characterized using 17 RAPD primers. Genetic diversity among these strains of Aschersonia was found. The clustering results showed that the genetic variability among interspecies was more than that among intraspecies of Aschersonia. In the constructed phylogenetic tree, these isolates were not clustered according to their geographic origins or hosts. Furthermore, sequences of the divergent domain at the 5′-end of the large subunit (LSU) in nuclear rRNA from the mitosporic entomogenous fungi were employed to analyse the phylogenetic relationships of 11 Aschersonia isolates. The relationships of interspecies or intraspecies shown in the phylogenetic tree were almost consistent with the results of the morphological study. Different species isolated from different geographic origins could be clearly distinguished in the tree. But there were no close relationships among species isolated from the same family or order of insect hosts. The tree indicated that isolate Aa, belonging to A. aleyrodis, was the same as Aa992 and Aa3.4485. Moreover, results of RAPD analyses were consistent with those of LSU nuclear rDNA analysis for the same isolates tested, which consequently indicates that both methods can be independently applied for classification and identification of Aschersonia.
In this study, inter-strain reconstructed embryos were produced by combining the female pronucleus of Kunming mouse (white) with male pronucleus of C57BL/6 strain (black). Metaphase II (MII) oocytes of Kunming mouse were enucleated and the zona pellucida was removed. Then, the enucleated oocytes were inseminated by capacitated sperm of C57BL/6 mouse in vitro. At the same time, MII oocytes of Kunming mouse were artificially activated using strontium chloride solution, which did not contain cytochalasin B. Finally, we removed the male pronucleus derived from C57BL/6 sperm and injected it into a parthenogenetically activated one-pronucleus oocyte by micromanipulation. The reconstructed 2-cell embryos were transplanted into the oviducts of 22 foster mother mice, each receiving about 20 embryos. In the end, seven healthy and live pups were born from one recipient.