Noninvasive preeclampsia prediction using plasma cell-free RNA signatures.

BACKGROUND: Preeclampsia, especially preterm preeclampsia and early-onset preeclampsia, is a life-threating pregnancy disorder, and the heterogeneity and complexity of preeclampsia make it difficult to predict risk and to develop treatments. Plasma cell-free RNA carries unique information from human tissue and may be useful for noninvasive monitoring of maternal, placental, and fetal dynamics during pregnancy. OBJECTIVE: This study aimed to investigate various RNA biotypes associated with preeclampsia in plasma and to develop classifiers to predict preterm preeclampsia and early-onset preeclampsia before diagnosis. STUDY DESIGN: We performed a novel, cell-free RNA sequencing method termed polyadenylation ligation-mediated sequencing to investigate the cell-free RNA characteristics of 715 healthy pregnancies and 202 pregnancies affected by preeclampsia before symptom onset. We explored differences in the abundance of different RNA biotypes in plasma between healthy and preeclampsia samples and built preterm preeclampsia and early-onset preeclampsia prediction classifiers using machine learning methods. Furthermore, we validated the performance of the classifiers using the external and internal validation cohorts and assessed the area under the curve and positive predictive value. RESULTS: We detected 77 genes, including messenger RNA (44%) and microRNA (26%), that were differentially expressed in healthy mothers and mothers with preterm preeclampsia before symptom onset, which could separate participants with preterm preeclampsia from healthy samples and that played critical functional roles in preeclampsia physiology. We developed 2 classifiers for predicting preterm preeclampsia and early-onset preeclampsia before diagnosis based on 13 cell-free RNA signatures and 2 clinical features (in vitro fertilization and mean arterial pressure), respectively. Notably, both classifiers showed enhanced performance when compared with the existing methods. The preterm preeclampsia prediction model achieved 81% area under the curve and 68% positive predictive value in an independent validation cohort (preterm, n=46; control, n=151); the early-onset preeclampsia prediction model had an area under the curve of 88% and a positive predictive value of 73% in an external validation cohort (early-onset preeclampsia, n=28; control, n=234). Furthermore, we demonstrated that downregulation of microRNAs may play vital roles in preeclampsia through the upregulation of preeclampsia-relevant target genes. CONCLUSION: In this cohort study, a comprehensive transcriptomic landscape of different RNA biotypes in preeclampsia was presented and 2 advanced classifiers with substantial clinical importance for preterm preeclampsia and early-onset preeclampsia prediction before symptom onset were developed. We demonstrated that messenger RNA, microRNA, and long noncoding RNA can simultaneously serve as potential biomarkers of preeclampsia, holding the promise of prevention of preeclampsia in the future. Abnormal cell-free messenger RNA, microRNA, and long noncoding RNA molecular changes may help to elucidate the pathogenic determinants of preeclampsia and open new therapeutic windows to effectively reduce pregnancy complications and fetal morbidity.

Microstructure, Hot Deformation Behavior, and Recrystallization Behavior of Zn-1Fe-1Mg Alloy under Isothermal Compression.

Nowadays, wrought zinc-based biodegradable alloys are favored by researchers, due to their excellent mechanical properties and suitable degradation rates. However, there are few research studies on their thermal deformation behavior at present. This study took Zn-1Fe-1Mg and explored its microstructural change, deformation, recrystallization behavior and processing map by means of the thermal simulation experiment, at temperatures ranging from 235 °C to 340 °C and strain rates ranging from 10-2 s-1 to 10 s-1. The constitutive model was constructed using the Arrhenius formula. The results indicated that the evolution of microstructure included the dynamic recrystallization (DRX) of the Zn matrix, the spheroidization of the Mg2Zn11 phase, and breaking of the FeZn13 phase. The subgrains observed within the deformed grain resulted mainly from continuous dynamic recrystallization (CDRX). The precipitated FeZn13 grains overlapped with the precipitated MgZn2 from the matrix, thus forming a spine-like structure at the phase interface. After compression, the alloy possessed a strong basal texture. Affected by the change of Zn twins, textural strength decreased at first and then increased as the deformation temperature rose. There was only a small unstable region in the processing map, indicating that the alloy exhibited good machinability.

Microstructure, Mechanical Properties, and in Vitro Corrosion Behavior of Biodegradable Zn-1Fe-xMg Alloy.

Zinc (Zn), one of the promising candidates for biodegradable implant materials, has excellent biocompatibility and biodegradability. In this study, as-cast Zn1FexMg (x ≤ 1.5 wt %) alloys were prepared to systematically explore the effects of magnesium (Mg) alloying on their microstructures, mechanical properties, and biodegradability. The microstructure of Zn1FexMg alloy consisted of Zn matrix, Zn + Mg2Zn11 eutectic structure, and FeZn13 phase. The addition of Mg not only promoted grain refinement of the alloy, but also improved its mechanical properties. The results of immersion tests showed that the addition of Mg accelerated microcell corrosion between different phases, and the modeling of the corrosion mechanism of alloys in simulated body fluid (SBF) solution was discussed to describe the interaction between different phases in the corrosion process. Zn1Fe1Mg possessed superior comprehensive mechanical properties and appropriate corrosion rate, and the values for hardness, tensile strength, yield strength, elongation, and corrosion rate were 105 HB, 157 MPa, 146 MPa, 2.3%, and 0.027 mm/a, respectively, thus revealing that Zn1Fe1Mg is a preferred candidate for biodegradable implant material.

[Preparation of the monoclonal antibody against human Bocavirus VP2 protein].

OBJECTIVE: To express and purify HBoV VP2 protein, and the monoclonal antibody against HBoV VP2 protein was prepared with hybridoma technique. METHODS: The HBoV VP2 cloned into vector pET-30a was expressed in E. coil. After purified by immobilized metal affinity chromatography, the BALB/c mouse was immunized with purified protein as antigen. The positive hybridoma cells were screened with hybridoma technique and ELISA assay. Isotype and titer of the monoclonal antibody were detected. RESULTS: The recombinant HBoV VP2 protein was expressed and purified, and then the monoclonal antibody was obtained with hybridoma technique. The titer of the IgG monoclonal antibody was up to 1:4 x 10(5). CONCLUSION: Monoclonal antibody against recombinant HBoV VP2 protein was prepared and the antibody titer was high. This work may provide a new method in rapid diagnosis and study of HBoV.