Blood biomarkers representing maternal-fetal interface tissues used to predict early-and late-onset preeclampsia but not COVID-19 infection

BackgroundA well-known blood biomarker (soluble fms-like tyrosinase-1 [sFLT-1]) for preeclampsia, i.e., a pregnancy disorder, was found to predict severe COVID-19, including in males. True biomarker may be masked by more-abrupt changes related to endothelial instead of placental dysfunction. This study aimed to identify blood biomarkers that represent maternal-fetal interface tissues for predicting preeclampsia but not COVID-19 infection. MethodsThe surrogate transcriptome of the tissues was determined by that in maternal blood, utilizing four datasets (n=1,354) which were collected before the COVID-19 pandemic. Applying machine learning, a preeclampsia prediction model was chosen between those using blood transcriptome (differentially expressed genes [DEGs]) and the blood-derived surrogate for the tissues. We selected the most predictive model by the area under receiver operating characteristic (AUROC) using a dataset for developing the model, and well-replicated in datasets either with or without intervention. To identify eligible blood biomarkers that predicted any-onset preeclampsia from the datasets but did not predict positives in the COVID-19 dataset (n=47), we compared several methods of predictor discovery: (1) the best prediction model; (2) gene sets by standard pipelines; and (3) a validated gene set for predicting any-onset preeclampsia during the pandemic (n=404). We chose the most predictive biomarkers from the best method with the significantly largest number of discoveries by a permutation test. The biological relevance was justified by exploring and reanalyzing low- and high-level, multi-omics information. ResultsA prediction model using the surrogates developed for predicting any-onset preeclampsia (AUROC of 0.85, 95% confidence interval [CI] 0.77 to 0.93) was the only that was well-replicated in an independent dataset with no intervention. No model was well-replicated in datasets with a vitamin D intervention. None of the blood biomarkers with high weights in the best model overlapped with blood DEGs. Blood biomarkers were transcripts of integrin-5 (ITGA5), interferon regulatory factor-6 (IRF6), and P2X purinoreceptor-7 (P2RX7) from the prediction model, which was the only method that significantly discovered the eligible blood biomarkers (n=3/100 combinations, 3.0%; P=.036). Most of the predicted events (73.70%) among any-onset preeclampsia were cluster A as defined by ITGA5 (Z-score [≥]1.1), but were only a minority (6.34%) among positives in the COVID-19 dataset. The remaining were the predicted events (26.30%) among any-onset preeclampsia or those among COVID-19 infection (93.66%) if IRF6 Z-score was [≥]-0.73 (clusters B and C), in which none was the predicted events among either late-onset preeclampsia (LOPE) or COVID-19 infection if P2RX7 Z-score was <0.13 (cluster B). Greater proportion of predicted events among LOPE were cluster A (82.85% vs. 70.53%) compared to early-onset preeclampsia (EOPE). The biological relevance by multi-omics information explained the biomarker mechanism, polymicrobial infection in any-onset preeclampsia by ITGA5, viral co-infection in EOPE by ITGA5-IRF6, a shared prediction with COVID-19 infection by ITGA5-IRF6-P2RX7, and non-replicability in datasets with a vitamin D intervention by ITGA5. ConclusionsIn a model that predicts preeclampsia but not COVID-19 infection, the important predictors were maternal-blood genes that were not extremely expressed, including the proposed blood biomarkers. The predictive performance and biological relevance should be validated in future experiments.

Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats / 生理学报

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

[Effective medicinal ingredients and screening of excellent germplasm in Rubus chingii].

In order to provide rationale for selection of good germplasm in Rubus chingii, main effective medicinal ingredients of green fruit such as gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside were measured using UPLC for the samples collected from Chun'an county of Zhejiang province, and such parameters as soluble solid contents of ripe fruit of some samples were also measured to study variation among individuals and correlation. It has been found that there were differences among individuals in the contents of gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside, which ranged from 0.010 2%-0.027 4%, 0.089 5%-0.291 1%, 0.010 5%-0.114 8%, 0.005 8%-0.041 2% and 0.010 9%-0.086 3%, respectively, with a CV of 18.60%, 27.02%, 44.23%, 44.17% and 47.29%, respectively. Gallic acid was positively correlated with ellagic acid, but negatively with kaempferol-3-rutinoside and astragalin significantly. Significantly positive correlation existed between kaempferol-3-rutinoside, astragalin and linden glycoside as well as between ellagic acid and fruit shape index of ripe fruit and between linden glycoside and the content of soluble solids. 51.35% of the individuals had a content of soluble solids more than 15%. Therefore, abundant variations have been found among individuals in effective medicinal ingredients in R. chingii, which shows great potential for selection, but only do 7.61% of the individuals meet the requirement of Chinese pharmacopoeia in terms of the contents of effective medicinal ingredients. Therefore, selection could be first performed in terms of fruit shape index of ripe red fruit, followed by the contents of ellagic acid and kaempferol-3-rutinoside measured. The individuals, in which the contents of effective medicinal ingredients don't meet the requirement of Chinese pharmacopoeia, could be considered for the selection in terms of edible fresh fruit.

[Microbial biodiversity in rhizospheric soil of Torreya grandis 'Merrillii' relative to cultivation history]. / ä¸åŒç§æ¤å¹´é™é¦™æ¦§æ ¹é™ åœŸå£¤å¾®ç”Ÿç‰©å¤šæ ·æ€§.

To examine the effects of different cultivation history (5 a,10 a, and 15 a) on soil microbial communities, we used Illumina sequencing to investigate the diversity and structure of soil bacterial and fungal communities from Torreya grandis 'Merrillii' fields. The results showed that bacterial Shannon index, the richness estimators Chao1 and ACE were lower in soil in 15 year-old stand than those in other cultivation histories, while Simpson index showed no significant variation. Results from bacterial community NMDS showed that cultivation history played a vital role in driving the changes of soil bacteria communitiy structure. The bacterial communities in 5 and 10 year-old stand had the similar composition. The variations of bacterial richness and diversity as well as community structure (comprised basically of Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi) were significantly correlated with soil organic matters, soil C/N, and total nitrogen. The fungi richness estimators of Chao1 and ACE were significantly decreased with increasing cultivation history. Shannon and Simpson indices were significantly higher in soil with 10 year-old stand than soils with other cultivation history. Fungal NMDS could be clustered in the same era. Fungal communities were comprosed of Ascomycota, Basidiomycota and Zygomycota. Changes in fungal richness/diversity and community structure were mainly controlled by the variation of soil organic matter. In conclusion, the predominant factors affecting soil microbial communities were the cultivation history, soil C/N, total nitrogen and organic matter, respectively.

Role of NF- κ B signaling pathway in airway inflammation of rats induced by atmospheric PM

Objective:To define the effect of PMMethods:Atmospheric PMResults:The organ coefficient of trachea in the group receiving 1.5 mg/kg PMConclusion:Atmospheric PM

Effect of opioid receptors on acute stress-induced changes in recognition memory / 生理学报

Although ample evidence has shown that acute stress impairs memory, the influences of acute stress on different phases of memory, such as acquisition, consolidation and retrieval, are different. Experimental data from both human and animals support that endogenous opioid system plays a role in stress, as endogenous opioid release is increased and opioid receptors are activated during stress experience. On the other hand, endogenous opioid system mediates learning and memory. The aim of the present study was to investigate the effect of acute forced swimming stress on recognition memory of C57 mice and the role of opioid receptors in this process by using a three-day pattern of new object recognition task. The results showed that 15-min acute forced swimming damaged the retrieval of recognition memory, but had no effect on acquisition and consolidation of recognition memory. No significant change of object recognition memory was found in mice that were given naloxone, an opioid receptor antagonist, by intraperitoneal injection. But intraperitoneal injection of naloxone before forced swimming stress could inhibit the impairment of recognition memory retrieval caused by forced swimming stress. The results of real-time PCR showed that acute forced swimming decreased the μ opioid receptor mRNA levels in whole brain and hippocampus, while the injection of naloxone before stress could reverse this change. These results suggest that acute stress may impair recognition memory retrieval via opioid receptors.

Accuracy Assessment of Three-dimensional Surface Reconstructions of In vivo Teeth from Cone-beam Computed Tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results.</p><p><b>METHODS</b>Fifty teeth from 18 orthodontic patients were assigned to three groups as NewTom VG 0.15 mm group (NewTom VG; voxel size: 0.15 mm; n = 17), NewTom VG 0.30 mm group (NewTom VG; voxel size: 0.30 mm; n = 16), and VATECH DCTPRO 0.30 mm group (VATECH DCTPRO; voxel size: 0.30 mm; n = 17). The 3D reconstruction models of the teeth were segmented from CBCT data manually using Mimics 18.0 (Materialise Dental, Leuven, Belgium), and the extracted teeth were scanned by 3Shape optical scanner (3Shape A/S, Denmark). Linear and volumetric deviations were separately assessed by comparing the length and volume of the 3D reconstruction model with physical measurement by paired t- test. Geometric deviations were assessed by the root mean square value of the imposed 3D reconstruction and optical models by one-sample t-test. To assess the influence of voxel size and CBCT system on 3D reconstruction, analysis of variance (ANOVA) was used (μ = 0.05).</p><p><b>RESULTS</b>The linear, volumetric, and geometric deviations were -0.03 ± 0.48 mm, -5.4 ± 2.8%, and 0.117 ± 0.018 mm for NewTom VG 0.15 mm group; -0.45 ± 0.42 mm, -4.5 ± 3.4%, and 0.116 ± 0.014 mm for NewTom VG 0.30 mm group; and -0.93 ± 0.40 mm, -4.8 ± 5.1%, and 0.194 ± 0.117 mm for VATECH DCTPRO 0.30 mm group, respectively. There were statistically significant differences between groups in terms of linear measurement (P < 0.001), but no significant difference in terms of volumetric measurement (P = 0.774). No statistically significant difference were found on geometric measurement between NewTom VG 0.15 mm and NewTom VG 0.30 mm groups (P = 0.999) while a significant difference was found between VATECH DCTPRO 0.30 mm and NewTom VG 0.30 mm groups (P = 0.006).</p><p><b>CONCLUSIONS</b>The 3D reconstruction from CBCT data can achieve a high linear, volumetric, and geometric accuracy. Increasing voxel resolution from 0.30 to 0.15 mm does not result in increased accuracy of 3D tooth reconstruction while different systems can affect the accuracy.</p>

Evaluation and discrimination of cortex Magnoliae officinalis produced in Zhejiang Province (Wen-Hou-Po) by UPLC-DAD-TOF-MS fingerprint.

An ultra performance liquid chromatography tandem TOF mass spectrometric (UPLC-DAD-TOF-MS) fingerprinting method was developed for the quality control and source discrimination of Cortex magnoliae officinalis produced in Zhejiang Province (Wen-Hou-Po). Twelve samples of Wen-Hou-Po collected from two species in five areas in Zhejiang Province of China were used to establish the fingerprint. Data were evaluated statistically using similarity analysis, hierarchical cluster analysis (HCA) and discriminant analysis (DA) in order to establish a similarity standard of fingerprint for quality control of Wen-Hou-Po, then to classify the Wen-Hou-Po samples and to identify key categorizing parameters. The similarity indexes were all above 0.95 between the reference chromatogram and that of each sample. By comparing the UV and MS data with those of the authentic standards and literature, nine main peaks in the fingerprints were identified. The result of hierarchical cluster analysis showed that the samples from two species in five areas could be divided into two distinct groups (the same as the groups of the samples divided by their species) based on their compositional fingerprints. A rapid and convenient discriminant function was then established to discriminate the species of unknown Wen-Hou-Po, and the cross validation result was 100%. In this study, the methods established are reliable, and could be used to evaluate the quality and to identify the species of Wen-Hou-Po in the future.

Studies of UPLC fingerprint for the identification of Magnoliae officinalis cortex processed.

This study was carried out with the objective of establishing Ultra Performance Liquid Chromatograph (UPLC) fingerprint for the identification of Magnoliae officinalis cortex processed. It was extracted by methanol using an ultrasonic extractor. Twelve samples of M. officinalis cortex produced in Zhejiang of China from different places and species were processed with ginger juice; sample solutions were determined by Waters UPLC equipped with BEH C(18) column and a DAD detector, gradient eluted with formic acid/methanol-formic acid/water as mobile phase. The flow rate was set at 0.3 ml(*) min(-1), while the column temperature was set at 30 degrees C, and the wavelength for detection was set at 240 nm. The characteristic of the common peaks of the UPLC fingerprint for M. officinalis cortex processed are obvious. Forty-one common peaks were detected and two of them were identified. The method of UPLC fingerprint established in this experiment was rapid and efficient. It is an effective means for the quality control of M. officinalis cortex processed.

[Study on correlation between effective ingredients of dogwood fruit from genuine producing regions and traits].

OBJECTIVE: In order to provide a theoretical foundation for the medically effective ingredient-based selection of elite cultivars in Comnus officinalis, a study has been conducted on the variation in medicinal effective ingredients of the fruit from the genuine producing areas, the correlation among effective medicinal ingredients and the correlation between effective ingredients and fruit shape as well as nutritional indexes. METHOD: The completely mature fruit was collected from the genuine producing areas Chunan county and Lin'an city of Zhejiang province. The contents of colchicine, ursolic acid and oleanolic acid were determined by HPLC, and vertical diameter/transversal diameter of the fruits, soluble solid matter and percentage of fresh flesh to the fruit were also measured. RESULT: (1) Ursolic acid, oleanolic acid, and colchicine in fruits ranged from 0.1010% to 0.4786%, 0.0149% to 0.1274% and 0.59% to 2.30%, respectively, and their RSD were 34.33%, 40.48% and 28.50%, respectively. (2) The correlation between effective ingredients and that between effective ingredients and fruit shape as well as nutritional indexes were as follows: the content of ursolic acid was significantly correlated with that of oleanolic acid with a correlation coefficient of 0.9796; both ursolic acid and oleanolic acid were in significantly negative correlation with soluble solid matter with a correlation coefficient of -0.5544 and -0.5118, respectively; colchicine was significantly associated with soluble solid matter with a correlation coefficient of 0.2412; colchicine, ursolic acid and oleanolic acid were in significantly negative correlation with the percentage of fresh flesh with a correlation coefficient of -0.2507, -0.2443 and -0.2406, respectively; three effective ingredients showed no correlation with the ratio of vertical diameter to transversal diameter of the fruit. CONCLUSION: There is a significant difference in effective ingredients among individual trees, which means that there is a big potential for selection of cultivars. Individual tree-based selection should be mainly adopted when effective ingredients are used as a main index in selection on the basis of the correlation among effective ingredients and that between effective ingredients and fruit shape as well as nutritional indexes, while ursolic acid could be combined with oleanolic acid to be used as an index and a preliminary screen could be conducted using soluble solid matter.