EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling†.

Recurrent implantation failure (RIF) patients exhibit poor endometrial receptivity and abnormal decidualization with reduced effectiveness and exposure to progesterone, which is an intractable clinical problem. However, the associated molecular mechanisms remain elusive. We found that EH domain containing 1 (EHD1) expression was abnormally elevated in RIF and linked to aberrant endometrial decidualization. Here we show that EHD1 overexpressed in human endometrial stromal cells significantly inhibited progesterone receptor (PGR) transcriptional activity and the responsiveness to progesterone. No significant changes were observed in PGR mRNA levels, while a significant decrease in progesterone receptor B (PRB) protein level. Indeed, EHD1 binds to the PRB protein, with the K388 site crucial for this interaction. Overexpression of EHD1 promotes the SUMOylation and ubiquitination of PRB, leading to the degradation of the PRB protein. Supplementation with the de-SUMOylated protease SENP1 ameliorated EHD1-repressed PRB transcriptional activity. To establish a functional link between EHD1 and the PGR signalling pathway, sg-EHD1 were utilized to suppress EHD1 expression in HESCs from RIF patients. A significant increase in the expression of prolactin and insulin-like growth factor-binding protein 1 was detected by interfering with the EHD1. In conclusion, we demonstrated that abnormally high expression of EHD1 in endometrial stromal cells attenuated the activity of PRB associated with progesterone resistance in a subset of women with RIF.

Reduced cadmium toxicity in rapeseed via alteration of root properties and accelerated plant growth by a nitrogen-fixing bacterium.

Cd accumulation in crops has become a global environmental problem because it endangers human health. Screening for microorganisms that can reduce Cd accumulation in crops is a possible measure to address this issue. However, success has been limited, and most previous work did not involve bacteria. In the present study, a strain of N-fixing bacteria (Burkholderia spp.) that exhibits high levels of Cd tolerance was screened. The ability of this bacterium to reduce Cd in rapeseed was then assessed in sterile hydroponic and open soil culture systems. In the hydroponic system, the Burkholderia inoculum promoted Cd fixation in rapeseed roots and thus reduced Cd enrichment in aboveground edible tissues (leaves). The mechanisms were related to increased activity of pectin methylesterase in root cell walls, and the transformation of the chemical form of root Cd from "active" (NaCl-extracted) to "inert" (HCl-extracted and residual Cd) states. Additionally, Burkholderia accelerated plant growth, thus shortening the period in which the plant is available for Cd absorption. In the soil culture system, Burkholderia also reduced Cd enrichment in rapeseed leaves in the presence of other microorganisms. Thus, the bacterial strain shows potential for broad application for reducing the accumulation of Cd in crops.

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

[Effect of Dimethyl Fumarate (DMF) on T-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL. METHODS: Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours. RESULTS: DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771). CONCLUSION: DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.

PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice.

Postsynaptic density protein-93 (PSD-93) plays an important role in ischemic brain injury through N-methyl-D-aspartate receptor (NMDAR)-triggered neurotoxicity. GTPase-activating protein for Ras (SynGAP) is a GAP specifically expressed in the central nervous system to regulate nerve development and synaptic plasticity. However, the link between PSD-93 and SynGAP and their role in ischemic brain injury remain elusive. Here, we showed that PSD-93 interacted with SynGAP and mediated SynGAP ubiquitination and degradation following ischemic brain injury. Proteasome inhibitor MG-132 could reverse the decrease of SynGAP protein level in wild-type mice following cerebral ischemia reperfusion through inhibiting SynGAP ubiquitination. Furthermore, NMDA receptor inhibitor MK801 could increase SynGAP protein level in wild-type mice following cerebral ischemia reperfusion. However, in PSD-93 knockout mice, MG-132 or NMDAR inhibitor had no significant effect on SynGAP expression. Both MG-132 and PSD-93 knockout reduced infarct volume and improved neurological deficit in mice at different time points after cerebral ischemia reperfusion. Furthermore, we identified that 670-685 amino acid sequence of SynGAP was essential to the binding of SynGAP to PSD-93, and designed a fusion peptide Tat-SynGAP (670-685aa) that could attenuate ischemic brain damage in wild-type mice. In conclusion, we provide the first evidence that PSD-93 directly interacts with SynGAP and mediates its ubiquitination and degradation to aggravate ischemic brain damage. Tat-SynGAP (670-685aa) may be considered as a candidate for treatment of acute ischemic stroke.

Catalytic hydrotreatment of kraft lignin into aromatic alcohols over nickel-rhenium supported on niobium oxide catalyst.

Direct hydrogenolysis of Kraft lignin was catalyzed over a series of supported Ni or Re catalysts in ethanol solvent. The best results showed that the oil yield of 96.70 wt% was obtained with less char formation at 330 °C for 3 h over 5Ni-5Re/Nb2O5 catalyst. Product analysis demonstrated that the monomer yield of 35.41 wt% was given under mild condition, and low-molecular-weight aromatic alcohols were the main component in the liquid products. Ethanol was found to be more effective in H2 production and facilitated the transformation of phenolic monomers to aromatic chemicals. The results confirmed that the optimal 5Ni-5Re/Nb2O5 catalyst had superior oxophilicity and appropriate acid sites, which improved the ability to directly remove the methoxyl and hydroxyl groups of lignin-derived phenolic compounds without aromatic ring hydrogenation. In addition, the temperature, time and solvent effects on the lignin depolymerization were also investigated.

Efficient and controllable alcoholysis of Kraft lignin catalyzed by porous zeolite-supported nickel-copper catalyst.

The alcoholysis of Kraft lignin was catalyzed by bimetallic Ni-Cu supported on H-Beta, HZSM-5, MAS-7, MCM-41 and SAPO-11 zeolite materials in isopropanol solvent. Results showed that a higher bio-oil yield of 98.80 wt% and monomer yield of 50.83 wt% without obvious char were achieved at 330 °C for 3 h over Ni-Cu/H-Beta catalyst. Isopropanol was found to be more effective in H2 generation and facilitated to the hydrodeoxygenation of lignin-derived phenolic compounds. Moreover, the composition of liquid products was also influenced by the acidity and pore structure of catalyst. The superior cycloalkanes yield was produced over Ni-Cu/H-Beta with larger pore size and more acidity. In contrast, a large number of cyclic ketones/alcohols and alkanes were obtained over other zeolites supported catalysts with smaller pore size and less acid content. Besides, the temperature, time and solvent effect on the lignin depolymerization were also researched.

Organic solvent extraction-assisted catalytic hydrothermal liquefaction of algae to bio-oil.

In this paper, we report our investigation into a two-step method of transformation of algae to bio-oil. Elemental analysis, gas chromatography-mass spectrometry and Fourier transform infrared spectroscopy were used to analyze bio-oil. First, organic solvent Soxhlet extraction and reflux extraction were used in the algal extraction step. Ethanol was proven to be the best solvent, and the addition of MgSO4 could transform acids to esters. In MgSO4 extraction oil, the yield of hexadecanoic acid ethyl ester was as high as 48.40%. Then, the residual algae powders through the catalytic hydrothermal liquefaction process were converted to bio-oil. Commercialized noble metal catalysts Pd/C, Pt/C, Ru/C and Rh/C combined with Pd/HZSM-5 were used in the second step. Rh/C performed the best in the catalytic hydrothermal liquefaction process, and the highest bio-oil yield of 50.98% and HHV of 30.67 MJ kg-1 were achieved. The oil yield through two steps was higher than that by a direct decomposition step. Also, the two-step method could achieve a higher energy conversion ratio of 85.61% and total energy of 81.09 kJ.

Correlation between hydrogen yield and product distribution in algae conversion through an isopropanol/water system.

This work reports a catalytic decomposition of algae to bio-oil over an isopropanol and water mixture system. The H2 yield was adjusted by changing the ratio between isopropanol and water. In this system, the introduction of formic acid was helpful to extend the yield range. Five noble metal supported catalysts were applied and Rh/C was proved to give the highest oil yield. A correlation was established between hydrocarbon yield and H2 yield. It was useful in predicting product distribution and helping to obtain desired products. EA, GC and GC-MS were applied in product analysis.

Clinical implication of triamcinolone in aqueous humor after depository sub-Tenon application.

PURPOSE: To determine the triamcinolone concentration in the aqueous humor after anterior sub-Tenon injection versus posterior sub-Tenon injection and the possible association between the levels of triamcinolone in the aqueous and the elevation in intraocular pressure (IOP). SETTING: University teaching hospitals at Wenzhou and Shanghai, China. DESIGN: Prospective case series. METHODS: The aqueous humor was sampled and triamcinolone quantitated after anterior sub-Tenon injection or posterior sub-Tenon injection in a cohort of patients and in experimental rabbits. Patients' IOPs were measured before and up to 3 months after triamcinolone acetonide injection. RESULTS: The study comprised 46 patients and 18 rabbits. The mean aqueous humor triamcinolone concentration in rabbit eyes and human eyes was significantly higher after an anterior sub-Tenon injection than that after a posterior sub-Tenon injection (rabbit eye: anterior sub-Tenon injection, 2.67 ng/mL ± 0.78 [SD] and posterior sub-Tenon injection 1.38 ± 0.48 ng/mL; human eye: 133.8 ± 149.2 ng/mL and 10.2 ± 10.9 ng/mL, respectively) (both P < .0001). After anterior sub-Tenon injection, the mean triamcinolone concentration in the aqueous humor was significantly higher in human eyes than in rabbit eyes (133.8 ± 149.2 ng/mL versus 11.0 ± 8.1 ng/mL) (P = .0003). The levels of triamcinolone in the human aqueous humor had a significant positive association with the elevation in IOP (ß = 0.12, P = .026). CONCLUSIONS: The triamcinolone level in aqueous humor was associated with IOP elevation after sub-Tenon application. Posterior sub-Tenon injection with a small injection volume of concentrated suspension offered a better targeted delivery and might significantly reduce steroid-associated IOP elevation.

Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects.

BACKGROUND: Congenital heart defects (CHD) are the most common form of malformation during embryonic development. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of maternal serum miRNAs and their correlation with fetal CHD. METHODOLOGY/PRINCIPLE FINDINGS: We systematically performed SOLiD sequencing followed by individual quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays to identify and validate the expression of maternal serum miRNAs at 18-22 weeks of gestation. Four miRNAs (miR-19b, miR-22, miR-29c and miR-375) were found to be significantly up-regulated in pregnant women with fetal CHD, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.79, 0.671, 0.767 and 0.693, respectively. Furthermore, the combination of the four miRNAs using multiple logistic regression analysis showed a larger AUC (0.813) that was more efficient for the early detection of fetal CHD. CONCLUSIONS/SIGNIFICANCE: We identified and validated a class of four maternal serum miRNAs which could act as novel non-invasive biomarkers for the prenatal detection of fetal CHD.

Anxiety and depression in parents of sick neonates: a hospital-based study.

AIMS AND OBJECTIVES: To investigate the prevalence of anxiety and depression in parents of hospitalised neonates and to analyse their relationship with other factors such as stress and social support, to provide evidence for targeted clinical interventions. BACKGROUND: The perinatal period, a special susceptibility to negative emotions, is a period that women and their spouses have to face. In this time, the fact that the neonates have to be hospitalised is no doubt a huge psychological stress to their parents. Little understanding of the hospitalisation environment, lacking awareness of neonatal diseases as well as concerns about the neonates' safety, can easily lead to negative emotions in parents. Under the influence of negative mood, parents could become irritable and vulnerable, which may do harm to their physical and mental health, impact family harmony and even result in ineffective communication with doctors, affecting the care of neonates. DESIGN: This study applied a cross-sectional study design. METHODS: The psychological status of 600 parents (400 fathers and 200 mothers) was assessed in the first week of the hospitalisation of neonates, using the Self-Rating Anxiety Scale, Self-Rating Depressive Scale, Social Support Rating Scale and Perceived Stress Scale. RESULTS: The results of the cross-sectional survey showed that 20% of fathers and 24% of mothers had symptoms of anxiety, while 30.8% of fathers and 35% of mothers had depressive symptoms. The total scores for anxiety and depression in these parents were significantly higher than the normal population (p<0.01). The level of social support and perceived stress were the most important factors relating to parental anxiety and depression. CONCLUSION: Parents of hospitalised neonates are more prone to suffer from negative emotions than normal population. Anxiety and depression are common emotions in these parents. However, the social support they receive is far from satisfactory, so timely and effective nursing interventions are essential. RELEVANCE TO CLINICAL PRACTICE: Health professionals should understand the mental health of parents with hospitalised neonates and take measures to reduce their psychological pressure so as to improve their care of the neonates, and help to maintain the harmony and stability of families and the whole society.

microRNA expression profiling of the developing mouse heart.

microRNAs (miRNAs) play an important role in regulating normal organ physiology and development. Many miRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the miRNA profile of the fetal mouse heart at 4 key time-points [embryonic day (E)12.5, E14.5, E16.5 and E18.5] in its development, by performing a sequencing by oligonucleotide ligation and detection (SOLiD) miRNA screen. The 4 time-points were designated as groups M1 (E18.5), M2 (E16.5), M3 (E14.5) and M4 (E12.5). miRNAs found to have consistent fold-changes of >2.0) between the 4 time-points were selected for further analysis. Ten miRNAs (mmu-miR-23b, mmu-miR-24, mmu-miR-23a, mmu-miR-375, mmu-miR-29a, mmu-miR-93, mmu-miR-21, mmu-miR-25, mmu-let-7b and mmu-miR-27b) that were the most highly expressed in the 4 groups, including the percentage >1% of total read counts, were identified. No miRNA was consistently downregulated or upregulated. There were 16 differentially expressed miRNAs between the later development group (M1+M2) and the early development group (M3+M4), which were validated by quantitative real-time PCR. Several members of the let-7 miRNA cluster (mmu-let-7a/7d/7e/7f) were upregulated in the later development group compared with the early development group. A network analysis of the predicted targets of mmu-let-7a/7d/7e/7f identified 5 target genes (FOXP1, TBX5, HAND1, AKT2 and PPARGC1A), known to be involved in cardiac development. Therefore, this study identified several miRNAs that are abundantly expressed in the developing heart, several of which are differentially expressed in the 4 time-points studied. Findings of this analysis may thus clarify the mechanisms of normal heart development and provide a physiological basis for future studies on congenital heart disease.

[Causes and countermeasure of complications in operative management of intra - articular fracture of calcaneus].

OBJECTIVE: To discuss the probable causes of the post-surgery complications with the intra-artcular fracture of calcaneus, the proper steps for prevention and solution. METHODS: Seventy-one patients (76 injured feet) included 49 males and 22 females aged from 19 to 56 years old (mean 35.6 years). According to Sanders' classification, 23 cases (24 injuried feet) belonged to type II, 36 (38 injured feet) were type III, the remain 12 (14 injured feet) met the criteria of type IV. All the patients received the operation of open reduction, autogenous bone grafting and internal fixation with stainless steel plates. RESULTS: Thirteen injuried feet developed early complications. Two injuried feet got the superficial layer of the wound disrupted and infected, I had the deep layer of the wound disrupted and infected. Cutaneous necrosis at the pointed end of the wound occurred in 7 cases. Another 1 developed osteomyelitis. Two cases suffered from sural nerve damage. Two injuried feet developed late complications, both of them suffered from arthritis of talocalcaneal joint. All the patients were followed up at least 6 months (ranged from 6 to 42 months, mean 19 months). According to Kerr's post-surgery evaluation criteria, 34 injuried feet were excellent, 32 were fine, 9 were acceptable, only 1 was bad. CONCLUSION: If proper measures are taken, the post-surgery complications of intra-articular fracture of calcaneus will be reduced. This requires us to be strict in selecting operation indication, to make a good plan and preparation, to select a right time for operation, to improve surgical skills and pay more attention to peri-surgery nursing. If complications happen, according measures should be taken in order to get a better outcome.