The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Objective:To observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.Methods:A retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C 3F 8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment. Results:One month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant ( Z=-3.727, -3.234; P<0.001, <0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes. Conclusions:Vitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.

Objective:To study the correlation between phosphatase and tensin homolog deleted on chromosome ten(PTEN), Syncytin-1 in preeclamptic placenta and maternal endothelial injury, trophoblast injury.Methods:From February 2015 to December 2017, 46 patients diagnosed as preeclampsia and delivered in Xiaolan Hospital Affiliated to Southern Medical University and 80 pregnant women with normal delivery in the same period were selected.Before delivery, maternal peripheral blood was collected and the content of endothelial injury markers was determined; after delivery, the placenta was retained and the expression of PTEN, Syncytin-1, apoptosis gene and the contents of oxidative stress markers were measured.Results:The mRNA expression of PTEN in placental tissue of preeclampsia was significantly higher than that of normal placental tissue( t=32.797, P<0.000), and the mRNA expression of Syncytin-1 was significantly lower than that of normal placental tissue( t=28.506, P<0.001); the content of ET-1 and sFlt-1 in the blood circulation of the maternal body of preeclampsia was significantly higher than thsoe of normal pregnant women( t=39.884, 40.243; all P<0.000) and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=0.674, 0.596; P=0.004, 0.007), negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=-0.615, -0.637; P<0.009, 0.008); the content of NO, PGI2, VEGF and PLGF were significantly lower than thse of normal pregnant women( t=30.944, 27.404, 32.827, 26.644; all P<0.001) and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=-0.648, -0.592, -0.537, -0.613; P=0.006, 0.009, 0.013, 0.007), positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=0.632, 0.572, 0.537, 0.654; P<0.010, 0.013, 0.015, 0.009); The contents of NOX4, MDA, 8-OHdG and the mRNA expression of Fas, FasL, Bax, GRP78, CHOP, Caspase-3 in placental tissue of preeclampsia was significantly higher than that of normal placental tissue( t=27.714, 27.704, 26.786, 27.964, 22.622, 25.496, 25.893, 30.837, 28.975; all P<0.001) and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=0.703, 0.651, 0.593, 0.628, 0.449, 0.552, 0.612, 0.569, 0.502; P<0.003, 0.007, 0.004, 0.006, 0.016, 0.010, 0.006, 0.012, 0.018), negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=-0.615, -0.714, -0.577, -0.548, -0.512, -0.585, -0.619, -0.495, -0.662; P<0.009, 0.001, 0.013, 0.015, 0.018, 0.011, 0.009, 0.023, 0.003); The contents of PrxII, PrxIII, SOD and mRNA expression of Bcl-2 in placental tissue of preeclampsia was significantly lower than that of normal placental tissue( t=26.115, 23.502, 17.194; all P<0.000) and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=-0.713, -0.657, -0.591, -0.642; P<0.001, 0.006, 0.009, 0.007), positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=0.562, 0.711, 0.682, 0.608, P<0.013, <0.001, 0.002, 0.008). Conclusion:The high expression of PTEN and the low expression of syncytin-1 in placenta of preeclampsia can aggravate the damage of endothelium and trophoblast.

Objective To evaluate the role of local gyrification index (LGI) in the early diagnosis of Alzheimer disease(AD). Methods Thirty‐five amnestic‐type mild cognitive impairment patients (aMCI group), 34 mild AD patients (mild AD group) and 33 healthy volunteers (normal control group) were studied. All patients underwent high resolution MRI examination and mini‐mental state examination (MMSE). Using surface‐based morphometry, the FreeSurfer was employed to access LGI of vertex over every participant′s whole cortical surface, then we calculated the mean LGI (mLGI) of each subject′s left and right hemisphere separately. Taking age, gender and educational year as covariance, analysis of covariance was used to compare the difference of mLGI of left and right brain among 3 groups, then Bonferroni was done between every two groups. Analysis of covariance was applied to compare the difference of LGI of every participant among 3 groups, and Monte Carlo method was employed to perform multiple comparison corrections. The correlations between the MMSE scores and LGIs of the three groups were analyzed. Results Compared with normal control group(left 3.03±0.12,right 3.02±0.13), the mLGI of hemispheres in mild AD group(left 2.94±0.11,right 2.93±0.10) decreased respectively(P<0.05). The difference of mLGI of hemispheres between aMCI group(left 2.96 ± 0.10, right 2.96 ± 0.09) and normal control group had no statistical significance(P>0.05). The difference of mLGI of hemispheres between aMCI group and mild AD group also had no statistical significance(P>0.05). The aMCI group showed decrease of LGI in some brain regions located at the right temporal lobe, bilateral frontal and parietal lobe compared with the normal control group. While compared with aMCI group, decreased LGIs was presented in some brain regions located at bilateral temporal, occipital, frontal lobe and the right parietal lobe of mild AD group. There was a positive correlation between MMSE scores and LGIs of some brain regions in the bilateral temporal, occipital lobe, the left frontal lobe and the right parietal lobe in the three groups. Conclusion LGI is conductive in the early diagnosis of AD and can serve as an imaging marker for monitoring disease progresses.

Objective: To investigate the antigenic epitope prediction method of hemagglutinin (HA) protein of influenza A (H1N1) virus. Methods: BALB/c mice were conventionally immunized with influenza H1N1 vaccine. The splenocytes from the immunized mouse were fused with SP2/0 mouse myeloma cell line, and then the antigen-specific monoclonal antibodies (mAbs) were obtained by screening hybridoma supernatants. ELISA blocking test was used to detect the blocking result of each monoclonal antibody, which was labeled by horseradish peroxidase (HRP). The light and heavy chain variable region genes of each antibody were cloned, the amino acid sites of the antibody-binding HA antigen epitope were predicted by computer simulation. Results: Three hybridoma cell lines of stable secreting anti-H1N1 influenza virus HA protein were obtained.Three mAbs were divided into two categories by ELISA blocking tests, which were divided into two categories according to preliminary results of computer simulation. Conclusions ELISA blocking test and computer simulation prediction can prove each other in predication of the antigenic epitopes of HA protein of H1N1 influenza virus.

Objective To study the value of relative cerebral blood flow(rCBF)changes in patients with amnestic-type mild cognitive impairment (aMCI)and mild Alzheimer disease(AD) using MRI pulsed arterial spin labeling(PASL).Methods A prospective study recruited 37 aMCI patients (aMCI group),30 mild AD patients(mild AD group) and 30 healthy volunteers (normal control group) from March 2011 to December 2013,MRI using PASL for cerebral perfusion imaging was performed and data of rCBF were collected.Taking age as covariate,analysis of variance (ANONA)was carried out to assess the difference of rCBF among all the three groups,then Bonferroni was done between every two groups.A follow-up examination using PASL was performed in the seventeen patients of the aMCI group.And paired t-test was used for comparing the longitudinal change of their rCBF data.Results Compared with the normal control group,the aMCI group showed significant increase of rCBF in bilateral posterior cingulate cortices and precuneus (cluster number 2 785,P＜0.05).While the mild AD group showed decrease of rCBF in the left inferior and superior parietal lobes,the angular,middle frontal lobe,as well as the right superior temporal lobe (cluster number 3 459-5 206,P＜0.05).When compared with the aMCI group,the mild AD group showed regional hypoperfusion in bilateral middle frontal lobes,the left precuneus,the right postcentral and inferior parietal lobe (cluster number 3 236-19 863,P＜0.05).In the longitudinal study of the 17 aMCI patients,an increased rCBF was found to coexist with reduced rCBF in the left inferior frontal and lateral occipital cortex,bilateral frontal poles and paracingulate gyrus,with hyperperfusion dominated.Increased rCBF was also detected in the left temporal lobe,the angular gyrus and precuneus,while decreased rCBF was present in the left putamen,the operculum and right corpus callosum (P＜0.05).Conclusions ASL perfusion imaging is a valuable method for dynamic monitoring of the cerebral perfusion changes in aMCI and AD patients.PASL will assist in finding a useful imaging biomarker for early diagnosis of AD.

Halohydrin dehalogenase is of great significance for biodegradation of the chlorinated pollutants, and also serves as an important biocatalyst in the synthesis of chiral pharmaceutical intermediates. A putative halohydrin dehalogenase (HheTM) gene from Tistrella mobilis KA081020-065 was cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinant enzyme was purified by Ni-NTA column and characterized. Gel filtration and SDS-PAGE analysis showed that the native form of HheTM was a tetramer. It exhibited the highest activity at 50 degrees C. The nature and pH of the buffer had a great effect on its activity. The enzyme maintained high stability under the alkaline conditions and below 30 degrees C. HheTM catalyzed the transformation of ethyl(S)-4-chloro-3-hydroxybutyrate in the presence of cyanide, to give ethyl (R)-4-cyano-3-hydroxybutyrate, a key intermediate for the synthesis of atorvastatin.
3-Hydroxybutyric Acid ; chemistry ; Bacterial Proteins ; genetics ; metabolism ; Cloning, Molecular ; Escherichia coli ; Hydrolases ; genetics ; metabolism ; Hydroxybutyrates ; chemistry ; Recombinant Proteins ; genetics ; metabolism ; Rhodospirillaceae ; enzymology ; genetics

Objective To investigate the efficiency of radiofrequency ablation (RFA) and microwave ablation (MWA) in treating uterine leiomyoma.Methods The clinical data of thermal ablation with RFA and MWA were retrospectively analyzed in 42 patients.All patients were followed up at least 12 months to observe the therapeutic effects after the treatment.The changes of vital signs and the size of uterine leiomyoma,the score of uterine leiomyoma symptom and quality of Iife(UFS-QOL) were compared after RFA or MWA,the two thermal ablations techniques of clinic efficiency and influence on complications were analyzed.Results 23 patients received treatment of RFA and 19 patients received MWA,the visual analogue scale(VAS)during operation and postoperation were statistically significant differences between the two groups(P ＜0.05).The sizes of uterine leiomyoma were significantly reduced after the thermal ablation,the differences of volume within two groups in different time were statistics significance(P ＜0.05),but there were no statistics significance differences between two groups (P ＞0.05).The symptoms in two groups were improved significantly after treatment and the scores of UFS-QOL were no statistics significance differences between two groups (P ＞0.05).Conclusions Both of RFA and MWA have significant clinic efficiency in treating uterine leiomyoma.Compared with MWA,RFA with lower adverse reactions during operation and postoperation.

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.

The in vitro antitumor activity of bakuchiol was exploited, compared with tamoxifen. The result of biological activities showed that bakuchiol could inhibit human breast cancer and the IC50 values were 2.89 x 10(-5) mol L(-1) and 8.29 x 10(-3) mol L(-1) against the cells line T-47D and MDA-MB-231 respectively. On the other hand, the key intermediate to synthesize bakuchiol was obtained by the method of Ireland-Claisen rearrangement. Comparing with traditional Claisen rearrangement, the reaction conditions are milder and the reaction reagents are safer.