Optically Tunable Electrical Oscillations in Oxide-Based Memristors for Neuromorphic Computing.

The application of hardware-based neural networks can be enhanced by integrating sensory neurons and synapses that enable direct input from external stimuli. This work reports direct optical control of an oscillatory neuron based on volatile threshold switching in V3O5. The devices exhibit electroforming-free operation with switching parameters that can be tuned by optical illumination. Using temperature-dependent electrical measurements, conductive atomic force microscopy (C-AFM), in situ thermal imaging, and lumped element modelling, it is shown that the changes in switching parameters, including threshold and hold voltages, arise from overall conductivity increase of the oxide film due to the contribution of both photoconductive and bolometric characteristics of V3O5, which eventually affects the oscillation dynamics. Furthermore, V3O5 is identified as a new bolometric material with a temperature coefficient of resistance (TCR) as high as -4.6% K-1 at 423 K. The utility of these devices is illustrated by demonstrating in-sensor reservoir computing with reduced computational effort and an optical encoding layer for spiking neural network (SNN), respectively, using a simulated array of devices.

Scalable Bright and Pure Single Photon Sources by Droplet Epitaxy on InP Nanowire Arrays.

High-quality quantum light sources are crucial components for the implementation of practical and reliable quantum technologies. The persistent challenge, however, is the lack of scalable and deterministic single photon sources that can be synthesized reproducibly. Here, we present a combination of droplet epitaxy with selective area epitaxy to realize the deterministic growth of single quantum dots in nanowire arrays. By optimization of the single quantum dot growth and the nanowire cavity design, single emissions are effectively coupled with the dominant mode of the nanowires to realize Purcell enhancement. The resonance-enhanced quantum emitter system boasts a brightness of millions of counts per second with nanowatt excitation power, a short radiation lifetime of 350 ± 5 ps, and a high single-photon purity with g(2)(0) value of 0.05 with continuous wave above-band excitation. Finite-difference time-domain (FDTD) simulation results show that the emissions of single quantum dots are coupled into the TM01 mode of the nanowires, giving a Purcell factor ≈ 3. Our technology can be used for creating on-chip scalable single photon sources for future quantum technology applications including quantum networks, quantum computation, and quantum imaging.

Farming on the Ocean via Desalination (FOOD).

Today, agricultural irrigation consumes the largest amount of freshwater globally, while humans are threatened by water scarcity. To eliminate the trade-off between hunger and thirst, here, we show off-grid maritime agriculture based on a floating solar-driven agro-desalination wooden dome. In this dome, part of the visible light is transmitted for photosynthesis, and the remaining solar energy drives solar desalination, providing enough water (>4 mm day-1) for irrigation. Based on this water-food synergy, the stages of germination and growth are demonstrated. This technology can, to a large extent, support food security and sustainable agriculture and, in principle, be used to create self-circulation systems at sea to help humans survive weather extremes such as floods and droughts.

Effectiveness of modified inferior oblique muscle belly transposition for V-pattern exotropia combined with mild to moderate inferior oblique muscle overaction.

AIM: To investigate the effectiveness of a modified inferior oblique muscle belly transposition for treatment of V-pattern exotropia combined with mild to moderate inferior oblique muscle overaction. METHODS: Thirteen cases (23 affected eyes) of V-pattern exotropia with inferior oblique muscle overaction (+ or ++) who underwent the modified inferior oblique muscle belly transposition procedure were retrospectively reviewed. The amount of V-pattern, grade of inferior oblique overaction, degree of vertical strabismus, abnormal head posture, and the fovea-disc angle were evaluated before and after surgery. RESULTS: The V-pattern was corrected in all cases, and the amount of V-pattern reduced by 17.85±5.13 prism diopter (PD) on average (t=16.07, P<0.001). The surgical cure rate for mild to moderate inferior oblique muscle overaction was 87.0% (20/23). The degree of the fovea-disc angle has a mean reduction of 5.45°±2.87° (t=3.95, P=0.003) after surgery. The mean vertical deviation in 5 cases with a small-angle hypertropia (5.23±3.06 PD) in the primary position reduced by 3.15±1.86 PD (t=6.10, P<0.001). No serious complications were observed. CONCLUSION: The modified inferior oblique muscle belly transposition procedure can effectively treat mild to moderate inferior oblique overaction and relieve the V-pattern, which is safe and easy to perform.

WTAP dysregulation-mediated HMGN3-m6A modification inhibited trophoblast invasion in early-onset preeclampsia.

Early-onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6-methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP-microarray, RNA-Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1-associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3'-UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.

Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease.

Objective: Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods: A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1ß (IL-1ß), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results: In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions: In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

Enhanced Contactless Salt-Collecting Solar Desalination.

Solar desalination is expected to solve the problem of global water shortage. Yet its stability is plagued by salt accumulation. Here, a paper-based thermal radiation-enabled evaporation system (TREES) is demonstrated to achieve sustainable and highly efficient salt-collecting desalination, featuring a dynamic evaporation front based on the accumulated salt layer where water serves as its own absorber via energy down-conversion. When processing 7 wt % brine, it continuously evaporates water at a high rate─2.25 L m-2 h-1 under 1 sun illumination─which is well beyond the input solar energy limit for over 366 h. It is revealed that such enhanced evaporation arises from the unique vertical evaporation wall of the paper-TREES, which captures the thermal energy from the heated bottom efficiently and gains extra energy from the warmer environment. These findings provide novel insights into the design of next-generation salt-harvesting solar evaporators and take a step further to advance their applications in green desalination.

Transcriptome and Metabolite Conjoint Analysis Reveals the Seed Dormancy Release Process in Callery Pear.

Seed dormancy transition is a vital developmental process for seedling propagation and agricultural production. The process is precisely regulated by diverse endogenous genetic factors and environmental cues. Callery pear (Pyrus calleryana Decne) is an important rootstock species that requires cold stratification to break seed dormancy, but the mechanisms underlying pear seed dormancy release are not yet fully understood. Here, we analyzed the transcriptome profiles at three different stages of cold stratification in callery pear seeds using RNA sequencing combined with phytohormone and sugar content measurements. Significant alterations in hormone contents and carbohydrate metabolism were observed and reflected the dormancy status of the seeds. The expressions of genes related to plant hormone metabolism and signaling transduction, including indole-3-acetic acid (IAA) biosynthesis (ASAs, TSA, NITs, YUC, and AAO) genes as well as several abscisic acid (ABA) and gibberellic acid (GA) catabolism and signaling transduction genes (CYP707As, GA2ox, and DELLAs), were consistent with endogenous hormone changes. We further found that several genes involved in cytokinin (CTK), ethylene (ETH), brassionolide (BR), and jasmonic acid (JA) metabolism and signaling transduction were differentially expressed and integrated in pear seed dormancy release. In accordance with changes in starch and soluble sugar contents, the genes associated with starch and sucrose metabolism were significantly up-regulated during seed dormancy release progression. Furthermore, the expression levels of genes involved in lipid metabolism pathways were also up-regulated. Finally, 447 transcription factor (TF) genes (including ERF, bHLH, bZIP, NAC, WRKY, and MYB genes) were observed to be differentially expressed during seed cold stratification and might relate to pear seed dormancy release. Our results suggest that the mechanism underlying pear seed dormancy release is a complex, transcriptionally regulated process involving hormones, sugars, lipids, and TFs.

EID1 plays a protective role in early-onset pre-eclampsia via promoting proliferation and invasion in trophoblast cells.

INTRODUCTION: Pre-eclampsia is a pregnancy-specific syndrome, which is partly due to abnormal proliferation and invasion of trophoblast cells. EP300 interacting inhibitor of differentiation 1 (EID1) participates in cell proliferation and invasion. This study aims to investigate the roles of EID1 in trophoblast cells and pre-eclampsia. MATERIAL AND METHODS: The expression of EID1 in placental tissues from 60 women with pre-eclampsia and 60 health pregnancies was detected by real-time PCR and immunohistochemical staining. EID1 was overexpressed or silenced by transfection of plasmid or siRNA in HTR-8/SVneo trophoblast cells, and then cell proliferation, cell cycle transition, migration, and invasion were determined by CCK-8 assay, flow cytometry, immunofluorescent staining, immunoblotting, and transwell assays. In addition, the activity of Akt/b-catenin signaling was measured by immunofluorescent staining and Western blot. RESULTS: EID1 mRNA level was decreased in placental tissues of pre-eclampsia patients, especially early-onset pre-eclampsia, accompanied by more severe clinical manifestation and a higher rate of fetal growth restriction (FGR). Gain- and loss-of-function experiments demonstrated that EID1 promoted proliferation and cell cycle transition, migration, and invasion in HTR-8/SVneo cells and its knockdown played opposite roles, suggesting that EID1 may be required for normal gestation. Akt/b-catenin signaling was activated after EID1 forced expression and deactivated after its silencing. CONCLUSIONS: EID1 promoted proliferation and invasion of cultured trophoblast cells with possible involvement of Akt/b-catenin signaling. These findings may provide novel insights for the diagnosis and treatment of early-onset pre-eclampsia in a clinic.

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.

Background: Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic. Methods: Human brain microvascular endothelial cells (HBMECs) were cultured in vitro, and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What's more, blood-brain barrier (BBB) integrity was also studied. Results: Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1. Conclusions: Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.

Sustainable Solar Evaporation from Solute Surface via Energy Downconversion.

Solar-powered interfacial evaporation, a cost-effective and ecofriendly way to obtain freshwater from contaminated water, provides a promising path to ease the global water crisis. However, solute accumulation has severely impacted efficient light-to-heat-to-vapor generation in conventional solar evaporators. Here, it is demonstrated that an interfacial solar thermal photo-vapor generator is an efficient light-to-heat photo-vapor generator that can evaporate water stably in the presence of solute accumulation. An energy downconversion strategy which shifts sunlight energy from visible-near infrared to mid infrared-far infrared bands turns water from transparent to its own absorber, thus changing the fixed evaporation surface (black absorber) in a traditional solar evaporator to a dynamic front (solute surface). Light reflected from the solute can be recycled to drive evaporation. The prototype evaporator can evaporate at a high speed of 1.94 kg m-2 h-1 during a persistent solute accumulation process for 32 h. Such an ability to produce purified water while recycle valuable heavy metals from waste water containing heavy metal ions can inspire more advanced solar-driven water treatment devices.

Sustainable Solar Evaporation while Salt Accumulation.

Solar-driven water evaporation, as a cost-effective and eco-friendly way to produce high-quality freshwater from saline water, is a burgeoning and promising force in the battle against global thirst. However, unsustainable vapor generation caused by salt accumulation has always plagued researchers. Here, it is revealed that a solar thermal photo vapor generator (STPV), which utilizes infrared photons as a heat source, can evaporate water stably in the presence of salt accumulation. Thanks to the low reflection of the wet salt in the infrared band and the porous structure of the salt layer, the energy can be used effectively and the vapor escapes without hindrance. The STPV evaporates water at a stable rate of 1.04-1.19 kg m-2 h-1 under 2 sun illumination for 8 h in a highly concentrated sea salt solution (20 wt %). In contrast, the evaporation rate of conventional solar thermal vapor generators (STVs) decreased by >50% in 1 h and ≈70% in 8 h. This finding could inspire the future development of more advanced solar evaporators so as to ease the global water scarcity.

Corrigendum: Long Non-Coding RNA Gas5 is Associated with Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21.

[This corrects the article DOI: 10.3389/fgene.2020.00188.].

Mutational analysis of the GATA4 gene in Chinese men with nonobstructive azoospermia.

As a crucial transcription factor for spermatogenesis, GATA-binding protein 4 (GATA4) plays important roles in the functioning of Sertoli and Leydig cells. Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility. However, whether GATA4 is associated with human azoospermia has not been reported. Herein, we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia (NOA). We identified a missense mutation (c.191G>A, p.G64E), nine single-nucleotide polymorphisms (SNPs), and one rare variant (c.*84C>T) in the 3´ untranslated region (UTR). Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes (claudin-11 and steroidogenic acute regulatory protein, Star), and the 3´ UTR rare variant c.*84C>T did not generate microRNA-binding sites to repress GATA4 expression. To our knowledge, this is the first report to investigate the association between GATA4 and azoospermia; our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

An integrated metabolic and transcriptomic analysis reveals the mechanism through which fruit bagging alleviates exocarp semi-russeting in pear fruit.

Fruit semi-russeting is an undesirable quality trait that occurs in fruit production. It is reported that preharvest fruit bagging could effectively alleviate fruit exocarp semi-russeting, but the physiological and molecular mechanisms remain unclear. In the present study, we performed an in-depth investigation into pear fruit semi-russeting from morphologic, metabolic and transcriptomic perspectives by comparing control (semi-russeted) and bagged (non-russeted) 'Cuiguan' pear fruits. The results showed that significant changes in cutin and suberin resulted in pear fruit semi-russeting. Compared with the skin of bagged fruits, the skin of the control fruits presented reduced cutin contents accompanied by an accumulation of suberin, which resulted in fruit semi-russeting; α, ω-dicarboxylic acids accounted for the largest proportion of typical suberin monomers. Moreover, combined transcriptomic and metabolic analysis revealed a series of genes involved in cutin and suberin biosynthesis, transport and polymerization differentially expressed between the two groups. Furthermore, the expression levels of genes involved in the stress response and in hormone biosynthesis and signaling were significantly altered in fruits with contrasting phenotypes. Finally, a number of transcription factors, including those of the MYB, NAC, bHLH and bZIP families, were differentially expressed. Taken together, the results suggest that the multilayered mechanism through which bagging alleviates pear fruit semi-russeting is complex, and the large number of candidate genes identified provides a good foundation for future functional studies.

Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis.

Placenta accreta spectrum (PAS) is a pathological condition of the placenta with abnormal adhesion or invasion of the placental villi to the uterine wall, which is associated with a variety of adverse maternal and fetal outcomes. Although some PAS-related molecules have been reported, the underlying regulatory mechanism is still unclear. Compared with the study of single gene or pathway, omics study, using advanced sequencing technology and bioinformatics methods, can increase our systematic understanding of diseases. In this study, placenta tissues from 5 patients with PAS and 5 healthy pregnant women were collected for transcriptomic and proteomic sequencing and integrated analysis. A total of 728 messenger RNAs and 439 proteins were found to be significantly different between PAS group and non-PAS group, in which 23 hub genes were differentially expressed in both transcriptome and proteome. Functional enrichment analysis showed that the differentially expressed genes were mainly related to cell proliferation, migration and vascular development. Totally 18 long non-coding RNA were found that might regulate the expression of hub genes. Many kinds of single nucleotide polymorphism, alternative splicing and gene fusion of hub genes were detected. This is the first time to systematically explore the hub genes and gene structure variations of PAS through integrated omics analysis, which provided a genetic basis for further in-depth study on the underlying regulatory mechanism of PAS.

ALG3-CDG: lethal phenotype and novel variants in Chinese siblings.

Congenital disorders of glycosylation (CDG) are a group of genetic, mostly multisystem disorders, which often involve the central nervous system. ALG3-CDG is one the some 130 known CDG. Here we report two siblings with a severe phenotype and intrauterine death. Whole-exome sequencing revealed two novel variants in ALG3: NM_005787.6:c.512G>T (p.Arg171Leu) inherited from the mother and NM_005787.6:c.511C>T (p.Arg171Trp) inherited from the father.

GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression.

Ferroptosis is an iron-dependent form of regulated cell death. GDF15 affects various properties of cancer cells, but the role of GDF15 in ferroptosis has not been reported. In the present study, we found that GDF15 knockdown led to decreased expression of SLC7A11, which is a key component of system Xc- and a regulator of ferroptosis, indicating that GDF15 might play important roles in ferroptosis. CCK8 assay showed that GDF15 knockdown promoted erastin-induced ferroptosis in MGC803 cells. qRT-PCR and western blotting results demonstrated that GDF15 inhibition attenuated the increased SLC7A11 expression induced by erastin. Further study revealed that GDF15 knockdown promoted the decreased level of extracellular glutamate and intracellular GSH as well as the increased level of lipid ROS in the presence of erastin in MGC803 cells. Overall, the study shows that GDF15 knockdown promotes erastin-induced ferroptosis in MGC803 cells by attenuating the expression of SLC7A11 and the function of system Xc-.

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21.

Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.

Circadian clock gene Clock is involved in the pathogenesis of preeclampsia through hypoxia.

OBJECTIVE: To study the effect of the circadian clock gene Clock on the biological behavior of trophoblasts and its role in the pathogenesis of preeclampsia. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of Clock mRNA. Western blot and immunohistochemistry were used to detect the expression and localization of Clock protein. CoCl2 was used to induce the hypoxic trophoblast cells. Cell invasion assay, wound healing assay and MTT assays were used to detect the invasion, migration, and proliferation ability. Reduced uterine perfusion pressure (RUPP) rat model was established by surgically clamping the abdominal aorta and uterine arteries. Transfection of si-Clock was used to silencing the expression of Clock. RESULTS: Clock mRNA expression was increased in placenta of preeclampsia and CoCl2-induced hypoxic trophoblasts, while protein was decreased. But the trend was opposite in RUPP rat models. Hypoxia can also change the expression rhythm of Clock. The proliferation, migration and invasion ability of trophoblasts decreased after hypoxia, while these abilities restored to near normal level after silencing Clock. CONCLUSION: The expression of Clock gene in human placenta tissue, hypoxia cell model and RUPP rat model suggests that it may regulate the biological behavior of trophoblast cells through hypoxia, and then participate in the pathogenesis of preeclampsia.