Search

Despite the elaborate varieties of iridescent colors in biological species, most of them are reflective. Here we show the rainbow-like structural colors found in the ghost catfish ( Kryptopterus vitreolus ), which exist only in transmission. The fish shows flickering iridescence throughout the transparent body. The iridescence originates from the collective diffraction of light after passing through the periodic band structures of the sarcomeres inside the tightly stacked myofibril sheets, and the muscle fibers thus work as transmission gratings. The length of the sarcomeres varies from ~1 μm from the body neutral plane near the skeleton to ~2 μm next to the skin, and the iridescence of a live fish mainly results from the longer sarcomeres. The length of the sarcomere changes by ~80 nm as it relaxes and contracts, and the fish shows a quickly blinking dynamic diffraction pattern as it swims. While similar diffraction colors are also observed in thin slices of muscles from non-transparent species such as the white crucian carps, a transparent skin is required indeed to have such iridescence in live species. The ghost catfish skin is of a plywood structure of collagen fibrils, which allows more than 90% of the incident light to pass directly into the muscles and the diffracted light to exit the body. Our findings could also potentially explain the iridescence in other transparent aquatic species, including the eel larvae ( Leptocephalus ) and the icefishes (Salangidae).

Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS). Trophoblast-specific AMPKα1-deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle-delivered A769662. Trophoblast glucose uptake was measured by 2-NBDG and 2-deoxy-d-[

Maternal circulating levels of the adipokine chemerin are elevated in preeclampsia, but its origin and contribution to preeclampsia remain unknown. We therefore studied (1) placental chemerin expression and release in human pregnancy, and (2) the consequences of chemerin overexpression via lentivirus-mediated trophoblast-specific gene manipulation in both mice and immortalized human trophoblasts. Placental chemerin expression and release were increased in women with preeclampsia, and their circulating chemerin levels correlated positively with the soluble Fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio, a well-known biomarker of preeclampsia severity. Placental trophoblast chemerin overexpression in mice induced a preeclampsia-like syndrome, involving hypertension, proteinuria, and endotheliosis, combined with diminished trophoblast invasion, a disorganized labyrinth layer, and up-regulation of sFlt-1 and the inflammation markers nuclear factor-κB (NFκB), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. It also led to embryo resorption, while maternal serum chemerin levels correlated negatively with fetal weight in mice. Chemerin overexpression in human trophoblasts up-regulated sFlt-1, reduced vascular endothelial factor-A, and inhibited migration and invasion, as well as tube formation during co-culture with human umbilical vein endothelial cells (HUVECs). The chemokine-like receptor 1 (CMKLR1) antagonist α-NETA prevented the latter phenomenon, although it did not reverse the chemerin-induced down-regulation of the phosphoinositide 3-kinase/Akt pathway. In conclusion, up-regulation of placental chemerin synthesis disturbs normal placental development via its CMKLR1 receptor, thereby contributing to fetal growth restriction/resorption and the development of preeclampsia. Chemerin might be a novel biomarker of preeclampsia, and inhibition of the chemerin/CMKLR1 pathway is a promising novel therapeutic strategy to treat preeclampsia.

Background Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanisms of lncRNAs in ESCC are still largely unknown and therapeutic attempts for in vivo targeting disease-associated lncRNA remain a challenge. Methods By RNA-sequencing analysis, we identified that LNLR-299G3.1 was a novel ESCC-associated lncRNA. Expression level of LLNLR-299G3.1 was determined by qRT-PCR and RACE. The functional significance of LLNLR-299G3.1 was assessed by knockdown or over-expression. plCSA-BP (placental chondroitin sulfate A binding peptide)-coated nanoparticles (NPs) were developed for targeting delivery of antisense oligonucleotide (ASO)-LLNLR-299G3.1 in vivo. RNA pull-down, mass spectrometry, RNA-seq, ChIRP-seq (chromatin isolation by RNA purification and sequencing), qRT-PCR assays, and rescue assays were performed to explore the mechanisms of LLNLR-299G3.1 in ESCC. Results LNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion. Silencing of LLNLR-299G3.1 with ASO resulted in opposite effects. Moreover, intravenous delivery of pICSA-NP loaded ASO (pICSA-ANPs) strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo. Mechanistically, LLNLR-299G3.1 bound to cancer-associated binding proteins and regulated the expression of cancer-related genes, including OSM, TNFRSF4, HRH3, and SSTR3. ChIRP-seq revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1. Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4. Conclusion LLNLR-299G3.1 was a novel oncogenic lncRNA that promoted ESCC malignancy through gene-chromatin interactions. In vivo targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

Background: Placental-like chondroitin sulfate A (pl-CSA) is exclusively expressed in cancerous and placental tissues and is highly correlated with the degree of malignancy. However, the mechanism through which pl-CSA regulates tumorigenesis and metastasis in choriocarcinoma remains unclear. Methods: Stable transfectants of the JEG3 choriocarcinoma cell line, including a negative control (NC) line and a cell line with knockout of the biosynthetic enzyme CS synthase-2 (ChSy-2) (ChSy-2-/-), were obtained using CRISPR/Cas9 systems and identified by immunofluorescence, flow cytometry, western blots and enzyme-linked immunosorbent assays (ELISAs). The proliferation, migration, invasion and colony formation of the cells were determined by a cell counting kit, scratch-wound assays, transwell assays and soft agar colony formation assays in vitro, respectively. The tumorigenesis and metastasis of choriocarcinoma were also investigated through two xenograft models in vivo. Results: The ChSy-2 protein in the ChSy-2-/-group was below the detection threshold, which was accompanied a significant reduction in the pl-CSA level. Reducing pl-CSA through ChSy-2 knockout significantly inhibited cell proliferation, migration, invasion and colony formation in vitro and tumorigenesis and metastasis of choriocarcinoma, with deceases in tumor volume and metastatic foci and a high percent survival compared to the NC in vivo. Conclusion: pl-CSA, as a necessary component of JEG-3 cells, was efficiently reduced through ChSy-2 knockout, which significantly inhibited the tumorigenesis and metastasis of choriocarcinoma. ChSy-2/pl-CSA could be alternative targets for tumor therapy.

Ever since the world entered the age of information, scientists have looked into the developments and applications of the growing prospects of machine learning and neural networks. In particular, the ability for deep learning machines to determine the risk, survivability, and prognosis of tumors based on medical cancer databases has intrigued healthcare researchers seeking to improve these algorithms in recent years. There are distinct aspects of medical procedures where artificial intelligence (AI) training can be applied; for example, the calculation of risk scores for patients based on mammographic screening, analysis of the presence of biomarkers like spermine and other polyamines in fluids surrounding tumors, genomic and epigenetic assessments to map genes that influence cancer expression, as well as the utilization of metabolomic data from FTIR spectroscopy of a patient’s biofluids to help make a more reproducible and conclusive diagnosis. The goal of this review is to discuss the progress of AI and deep learning in clinical procedures and applications in recent years and evaluate the efficacy of certain AI methods for tumor diagnosis, prognosis, and prediction based on patient information from available medical databases.

Preeclampsia, a major human pregnancy-specific disorder, leads to maternal and fetal morbidity and mortality. Here we reported that 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme that degrades active glucocorticoids, is one of the key factors that contributes to preeclampsia development. In the pregnant rat model, we firstly confirmed that administration of 11β-HSD2 inhibitor carbenoxolone (CBX) subcutaneously or by placenta-targeted delivery system could lead to a decrease in placental 11β-HSD2 expression and activity and an increase in corticosterone level in placenta and maternal circulation. Then, we showed that subcutaneous administration and placenta-targeted delivery of CBX resulted in the hallmark of preeclampsia-like features including hypertension, proteinuria, renal damages as well as elevated circulatory soluble fms-like tyrosine kinase 1 (sFlt1) and increased sFlt1/placental growth factor (PlGF) ratio in pregnant rats. These animals displayed decreased trophoblast invasion in uterus, impaired spiral artery remodeling, and reduced placental blood flow. Preeclampsia-like features could also be induced by administration of dexamethasone in pregnant rats. In the cultured human trophoblast models, we found that cortisol only inhibited migration and invasion of the extravillous trophoblasts with 11β-HSD2 knockdown, and promoted sFlt1 release in the cultured syncytiotrophoblasts with 11β-HSD2 knockdown. Furthermore, we elucidated that cortisol stimulated a disintegrin and metalloprotease (ADAM)17 expression in placentas, thereby promoting sFlt1 release in placenta. Collectively, our study provided the evidence that placental 11β-HSD2 dysfunction plays a key role in the development of preeclampsia and immediately identified innovative target to counteract preeclampsia.

Surface oxygen vacancies (V

Rational design and controllable synthesis of efficient and robust electrocatalysts for hydrogen evolution reaction (HER) remain a critical challenge for the renewable energy economy. Herein, heter...

Rationale: Placental-like chondroitin sulfate A (pl-CSA) is known to be exclusively synthesized in multiple cancer tissues and associated with disease severity. Here, we aimed to assess whether pl-CSA is released into bio-fluids and can serve as a cancer biomarker. Methods: A novel ELISA was developed to analyse pl-CSA content in bio-fluids using pl-CSA binding protein and an anti-pl-CSA antibody. Immunohistochemical staining of tissue chips was used as the gold standard control. Results: The developed ELISA method was specific and sensitive (1.22 μg/ml). The pl-CSA content was significantly higher in lysates and supernatants of cancer cell lines than in those of normal cell lines, in plasma from mouse cancer models than in that from control mice, and in plasma from patients with oesophageal, cervical, ovarian, or lung cancer than in that from healthy controls. Similar to the tissue chip analysis, which showed a significant difference in pl-CSA positivity between cancer tissues and normal adjacent tissues, the plasma pl-CSA analysis had 100% sensitivity and specificity for differentiating oesophageal and lung cancer patients from healthy controls. Importantly, in oesophageal and lung cancer patients, the pl-CSA content was significantly higher in late-stage disease than in early-stage disease, and it dramatically decreased after surgical resection of the tumour. Conclusion: These data indicate a direct link between plasma pl-CSA content and tumour presence, indicating that plasma pl-CSA may be a non-invasive biomarker with clinical applicability for the screening and surveillance of patients with multiple types of solid tumours.

Tetracycline (TC) is considered one of the most widely used antibiotic medicines, and ranks the second highest in global production and usage among all antibiotics. In this study, palladium nanoclusters (Pd NCs) have been successfully synthesized using polyvinylpirrolidone (PVP) as a capping agent and an ultrasensitive photoluminescent nanosensor for TC, and was first constructed based on an internal filtration effect causing fluorescence quenching of Pd NCs. The as-synthesized Pd NCs have high fluorescence intensity, good stability at extreme pH, high ionic strength, and excellent stability in light (under UV irradiation), and its fluorescence quantum yield (QY) was up to 5.9%. The fluorescence ratio of I/I0 linearly decreases with the increase in the concentrations of TC in the range from 0 nM to 220 nM in an aqueous buffer with the detection limit of 0.03 nM. The ultrasensitive detection of TC was also successfully realized in the spiked samples of honey with good recoveries. The advantages of this method include simplicity, rapidity, high sensitivity, high selectivity and cost efficiency.

Environmental catalysis has drawn a great deal of attention due to its clean ways to produce useful chemicals or carry out some chemical processes. Photocatalysis and electrocatalysis play important roles in these fields. They can decompose and remove organic pollutants from the aqueous environment, and prepare some fine chemicals. Moreover, they also can carry out some important reactions, such as O2 reduction reaction (ORR), O2 evolution reaction (OER), H2 evolution reaction (HER), CO2 reduction reaction (CO2RR), and N2 fixation (NRR). For catalytic reactions, it is the key to develop high-performance catalysts to meet the demand for targeted reactions. In recent years, two-dimensional (2D) materials have attracted great interest in environmental catalysis due to their unique layered structures, which offer us to make use of their electronic and structural characteristics. Great progress has been made so far, including graphene, black phosphorus, oxides, layered double hydroxides (LDHs), chalcogenides, bismuth-based layered compounds, MXenes, metal organic frameworks (MOFs), covalent organic frameworks (COFs), and others. This content drives us to invite many famous groups in these fields to write the roadmap on two-dimensional nanomaterials for environmental catalysis. We hope that this roadmap can give the useful guidance to researchers in future researches, and provide the research directions.

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.

Developing efficient metal-free catalysts to achieve electrochemical synthesis of hydrogen peroxide (H2O2) is crucial for substituting traditional energy-intensive anthraquinone process. Heteroatom-doped carbon materials have shown great potential toward 2e-pathway for catalyzing oxygen reduction to hydrogen peroxide (ORHP). However, conventional nanocarbon electrocatalysts show slow kinetics toward ORHP due to the weak binding strength with OOH* intermediate, resulting reduction of O2 to H2O. Here, sulfur and nitrogen dual-doped graphene (SNC) electrocatalyst consisting of S-C-N-C functional group are synthesized through hydrothermal self-assembly and nitridation processes with thiourea as sulfur source. In S-C-N-C functional group, pentagon-S and pyrrolic-N are covalently grafted onto the edge of graphene and produce marginal carbon ring defects, which provide highly active sites for catalyzing ORHP. The obtained SNC catalysts deliver an outstanding ORHP activity and selectivity for H2O2 production, while retaining remarkable stability. The experimental and computational results reveal that marginal S-C-N-C functional groups afford an appropriate adsorption strength with OOH* intermediate and a low reaction barrier as well, which are essential for the activity of ORHP.

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds.

Preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of PE, the exact cause for the disease development is still unclear. Recently, studies showed that genetic deletion of ELABELA (ELA, also known as APELA) could induce PE-like symptoms in mice. However, the role of ELA in the disease development of PE remains elusive. Our objective was to measure the changes of ELA levels in maternal serum, urine, and placenta from preeclamptic pregnant women and healthy pregnant women and evaluate the correlation between ELA levels and the occurrence of PE. Additionally, we investigated the effect of ELA on the migration and proliferation of human trophoblast cells. ELA levels are significantly decreased in late-onset PE pregnancies compared with normal pregnancies. The mRNA and protein expressions of ELA and the apelin receptor (APLNR or APJ) in late-onset PE placental tissues are also decreased. Furthermore, our in vitro study showed that the addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which were inhibited by the APJ-specific antagonist ML221. Our study identified ELA as significantly decreased in late-onset PE; therefore, it might play an important role in the pathogenesis of late-onset PE.

Developing earth-abundant catalysts for overall water splitting is important to sustainable energy conversion technologies. However, selectively exposing active surface and judiciously optimizing nanostructure remain challenging for high-performance electrocatalysts. Herein, (003)-facet-exposed Ni3S2 nanoporous thin films (NTFs) on nickel foil are synthesized through anodization and vapor-sulfurization strategies. The Ni3S2 NTFs exhibit low onset overpotentials of 48 and 152 mV, and require overpotentials of 135 and 175 mV to achieve a benchmark of 10 mA cm–2 towards alkaline hydrogen and oxygen evolution, respectively. Remarkably, an electrolyzer assembled by Ni3S2 NTFs as both anode and cathode can deliver a water-splitting current density of 10 mA cm–2 at 1.611 V. Experimental and theoretical results indicate that the controllable hollow nanoporous spheres and low-coordinated Ni3-triangles on Ni3S2(003) facet synergistically contribute to the electrocatalytic activity.

Beryllium (Be) has high ionization energy (9.32 eV) with the greatest degree of covalency in the group IIA elements, and BeO4 tetrahedra (and BeO3 triangles) with covalent character are generally presented in beryllates. An unprecedented BeO6 trigonal prism with ultralong Be-O bonds as well as a BeO4 common tetrahedron is discovered in a new deep ultraviolet crystal Li13BeBe6B9O27 (LBeBBO) with a ∞2[Be6B9O33] double-layer framework. The BeO6 unit and its bond character are verified by an isostructural crystal Li13(Mg0.45Be0.55)Be6B9O27, while the orbital theory and charge density difference further clarify the ionic character of the BeO6 unit. Phonon dispersion confirms the structural stability of LBeBBO.

A new and highly-efficient electrocatalyst, constructed by surface enwraped Co nanocrystyals (NCs) embedded into 2-dimensional N-doping graphitized carbon layer (Co@NC), is synthesized by simple one-pot thermal treatment of complex Co(tzbc)2(H2O)4 (tzbc = 4-(1H-1,2,4-triazol-1-yl) benzoate). The utilization of stoichiometrically clear Co(tzbc)2(H2O)4 as precursor could reap following benefits: i) sp2 carbon and nitrogen in tzbc groups could directly convert to N-doping graphitized carbon; ii) metallic Co NCs formed from the thermal reduction of Co2+ in Co(tzbc)2(H2O)4, which can subsequently catalyze the graphitization of the obtained carbons, avoiding additional reducing agent or using potentially dangerous atmosphere; iii) most importantly, complex precursor is easily available and could synthesize in a large scale by simple stirring reaction. As a result, the Co@NC catalyst exhibits excellent activity and stability toward both hydrogen and oxygen evolution reactions (HER and OER, respectively), approaching electrocatalytic performance shown by state-of-the-art Pt and RuO2. Such excellent HER and OER activities are attributed to the synergistic effect of the surface enwraped cobalt nanocrystyals and high conductivity of N-doped graphitized carbon.

The surface reconstruction of oxygen evolution reaction (OER) catalysts has been proven favorable for enhancing its catalytic activity. However, what is the active site and how to promote the active species generation remain unclear and are still under debate. Here, the in situ synthesis of CoNi incorporated Fe

The W1Mo1-NG dual-atom catalyst enables Pt-like activity and ultrahigh stability for hydrogen evolution reaction., Single-atom catalysts (SACs) maximize the utility efficiency of metal atoms and offer great potential for hydrogen evolution reaction (HER). Bimetal atom catalysts are an appealing strategy in virtue of the synergistic interaction of neighboring metal atoms, which can further improve the intrinsic HER activity beyond SACs. However, the rational design of these systems remains conceptually challenging and requires in-depth research both experimentally and theoretically. Here, we develop a dual-atom catalyst (DAC) consisting of O-coordinated W-Mo heterodimer embedded in N-doped graphene (W1Mo1-NG), which is synthesized by controllable self-assembly and nitridation processes. In W1Mo1-NG, the O-bridged W-Mo atoms are anchored in NG vacancies through oxygen atoms with W─O─Mo─O─C configuration, resulting in stable and finely distribution. The W1Mo1-NG DAC enables Pt-like activity and ultrahigh stability for HER in pH-universal electrolyte. The electron delocalization of W─O─Mo─O─C configuration provides optimal adsorption strength of H and boosts the HER kinetics, thereby notably promoting the intrinsic activity.

Background Stroke outpatients have a high risk of falling. However, fall prevention measures in the community are insufficient to effectively reduce the fall rate among outpatients with stroke. We aimed to determine the correlation between fall prevention knowledge and behavior among outpatients with stroke and provide new strategies for community fall prevention. Methods We recruited 124 patients with stroke who were followed up in the outpatient department of a tertiary hospital in Zhuhai, China. Patients were assessed using a general information questionnaire, a fall prevention knowledge questionnaire for patients with stroke, and the Stroke Fall Prevention Behavior Scale. IBM SPSS 22.0 software was used for statistical analysis. Results The median fall prevention knowledge was 82.76 (68.97, 93.10) points, out of 100. The mean (SD) score for fall prevention behavior was 2.90 (0.52; range, 1-4) points. Fall prevention knowledge scores were positively related to those fall prevention behavior (Spearman r = 0.454, P Conclusion Levels of fall prevention knowledge among outpatients with stroke were adequate, and this population had medium to high levels of fall prevention behavior. Better knowledge was accompanied with better prevention of falls. However, whether enriching the knowledge could lead to improvement of fall prevention is still undetermined.

Accumulated evidence has shown that pre-eclampsia (PE) is related to both maternal and utero-placental antiangiogenesis and inflammation. Remarkably, an elevated cell-free fetal DNA (cffDNA) level has been found in maternal circulation; however, it remains unclear whether this DNA can induce activation of cytosolic DNA sensor signaling pathways and lead to the development of PE. In this study, we found that trophoblast cells constitutively expressed the cytosolic DNA sensors, absent in melanoma 2 (AIM2) and interferon-inducible protein 16 (IFI16). The cffDNA and pro-inflammatory and antiangiogenic factors were present at higher concentrations in PE compared with the control group and correlated with the severity of PE. DNA stimulation significantly increased the AIM2 and IFI16 levels, consistent with the elevated AIM2 and IFI16 expression in women with PE, and elicited increased production of AIM2-mediated interleukin IL-8 (IL-8), IL-6 and CC chemokine ligand 2 (CCL2) and IFI16-mediated sEndoglin, sFlt-1 and CXCL10. Furthermore, enhancement of the inflammatory response was found to be induced by DNA exposure, but DNA exposure did not induce PE-like symptoms in pregnant mice. It is possible that elevated cffDNA could reflect the degree of placental damage and trigger cytosolic DNA sensor activation, which disrupts the immunity balance and, consequently, contributes to inflammatory and antiangiogenic responses. In conclusion, the results of this study suggest that circulating cffDNA levels are increased in preeclamptic women and act through AIM2 and IFI16 activation to promote the production of pro-inflammatory and antiangiogenic factors, which correlate with the severity of the disease, and may offer insights into the etiology and pathogenesis of PE.

R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of β-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.

Breakthroughs in cancer management result from the development of drugs that can be used for early diagnosis and effective treatment. Surgery, chemotherapy, radiotherapy and hormone therapy are the main anticancer therapies. However, traditional cancer chemotherapy is associated with serious systemic side effects. Nanoparticles (NPs) provide an effective solution for cancer treatment via the targeted delivery of drugs to cancer cells, while minimizing injury to normal cells. Glycosaminoglycan‑placental chondroitin sulfate A (plCSA) is expressed in a number of tumor cells and trophoblasts. A plCSA‑binding peptide (plCSA‑BP) was isolated from malaria protein VAR2CSA, which can effectively promote the binding of lipid polymer NPs to tumor cells, thereby significantly enhancing the anticancer effect of encapsulated drugs. Brusatol is an important compound derived from Brucea javanica that exerts a multitude of biological effects, including inhibiting tumor cell growth, reducing the reproduction of malaria parasites, reducing inflammation and resisting virus invasion. In the present study, brusatol‑loaded NPs (BNPs) or coumarin 6 NPs (CNPs), plCSA‑BP and scrambled control peptide‑bound BNPs or CNPs were prepared. Ovarian cancer cells (SKOV3), endometrial cancer cells (HEC‑1‑A) and lung cancer cells (A549) were treated with the NPs. The uptake of plCSA‑CNPs by tumor cells was found to be markedly higher compared with that of other types of NPs. Further studies demonstrated that the plCSA‑BNPs promoted the apoptosis of cancer cells more effectively and inhibited their proliferation, invasion and migration, accompanied by downregulation of matrix metalloproteinase (MMP)‑2, MMP‑9 and B‑cell CLL/lymphoma 2 (BCL2) levels, but upregulation of BCL2‑associated X protein BAX and cleaved caspase‑3 levels. The results demonstrated the potential of brusatol delivered by plCSA‑modified NPs as a chemotherapeutic agent for the targeted therapy of tumors by regulating the BCL2, BAX, cleaved caspase‑3, MMP‑2 and MMP‑9 pathways, and indicated that it may be an effective and safe strategy for the treatment of various tumors.

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

Studies have shown that sFlt-1 overproduction stimulated by excess VEGF of deciduous origin in trophoblasts can cause preeclampsia. However, the mechanism underlying how VEGF regulates sFtl-1 expression in trophoblasts remains unknown. To address this issue, JEG3 and HTR-8/SV neo (HTR8) trophoblast cell lines were used to investigate the signaling pathways involved in the regulation of sFlt-1 production via VEGF overexpression in vitro. JEG3 (VEGF-GFP-JEG3, V-J) and HTR8 (VEGF-GFP-HTR8, V-H) cells overexpressing VEGF165 were established by infecting the JEG3 and HTR8 cell lines with lentivirus expressing VEGF165. Both the mRNA and protein levels of VEGF and sFlt-1 were dramatically up-regulated in the V-J and V-H cells compared to the JEG3 and HTR8 cells, and they were significantly decreased after treatment with an Flt-1 receptor inhibitor (MK-2461), a KDR receptor inhibitor (XL-184), or an Flt-1 and KDR receptor inhibitor (ABT-869). The mRNA levels of sFlt-1, Flt-1, and KDR were increased in V-H cells after treatment, and the VEGF-A mRNA levels were also elevated. The migration and invasion abilities of JEG3 and HTR8 cells were decreased after VEGF overexpression, and this reduction could be reversed with VEGF receptor inhibitor treatment. In addition, after the different treatments, the cell migration rates of V-J cells were significantly increased compared with the control treatment. Taken together, these results indicate that sFlt-1 up-regulation by VEGF may be mediated by the VEGF/Flt-1 and/or VEGF/KDR signaling pathways. However, elucidating which pathway plays this key role requires further investigation.

Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to other cell types in the placenta or to CSA-expressing cells in other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option.

The abundant water resources from the earth are natural feedstocks for the electrolysis of water to produce hydrogen, and there is an urgent need for an efficient and stable catalyst for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Exploration of noble-metal-free, highly-efficient and durable bifunctional catalysts for HER and OER remains a challenge. In this work, Co-Ta3N5 catalysts were successfully prepared by in situ confined growth of active catalytic species within porous nanofilm using three-dimensional (3D) tantalum nitride (Ta3N5) porous nanofilm as templates. After electrochemical testing, we found that Co-Ta3N5 nanohybrid exhibits excellent OER and HER performance. Benefiting from the 3D composite nanostructures, the catalysts have excellent electron conduction rates and sufficient active sites, the Co-Ta3N5 nanocomposites nitrided at 800 °C exhibits relatively good catalytic activity for HER in acidic (low overpotential of 59.1 mV at 10 mA cm−2, small Tafel slope of 58 mV dec−1) and alkaline (low overpotential of 93 mV at 10 mA cm−2, Tafel slope of 97 mV dec−1) media, respectively. Co-Ta3N5-800 also exhibits relatively good catalytic activity for OER with low overpotentials 358 mV at 10 mA cm−1 in 1M KOH and the Tafel slope of 58.5 mV dec−1. Additionally, Co-Ta3N5-800 possesses excellent catalytic performance, and its catalytic performance with almost no degradation in catalytic performance after severe electrochemical tests, which ascribe to the structure of cobalt nanoparticles that confined-growth in Ta3N5 nanotubes. This discovery may pave a new avenue toward the development of robust inexpensive electrocatalysts for OER and HER.

The drive for significant advancement in battery capacity and energy density inspired a revisit to the use of Li metal anodes. We report the use of a seamless graphene–carbon nanotube (GCNT) electrode to reversibly store Li metal with complete dendrite formation suppression. The GCNT-Li capacity of 3351 mAh g–1GCNT-Li approaches that of bare Li metal (3861 mAh g–1Li), indicating the low contributing mass of GCNT, while yielding a practical areal capacity up to 4 mAh cm–2 and cycle stability. A full battery based on GCNT-Li/sulfurized carbon (SC) is demonstrated with high energy density (752 Wh kg–1 total electrodes, where total electrodes = GCNT-Li + SC + binder), high areal capacity (2 mAh cm–2), and cyclability (80% retention at >500 cycles) and is free of Li polysulfides and dendrites that would cause severe capacity fade.

Mo2C nanocrystals (NCs) anchored on vertically aligned graphene nanoribbons (VA-GNR) as hybrid nanoelectrocatalysts (Mo2C–GNR) are synthesized through the direct carbonization of metallic Mo with atomic H treatment. The growth mechanism of Mo2C NCs with atomic H treatment is discussed. The Mo2C–GNR hybrid exhibits highly active and durable electrocatalytic performance for the hydrogen-evolution reaction (HER) and oxygen-reduction reaction (ORR). For HER, in an acidic solution the Mo2C–GNR has an onset potential of 39 mV and a Tafel slope of 65 mV dec–1, and in a basic solution Mo2C–GNR has an onset potential of 53 mV, and Tafel slope of 54 mV dec–1. It is stable in both acidic and basic media. Mo2C–GNR is a high-activity ORR catalyst with a high peak current density of 2.01 mA cm–2, an onset potential of 0.93 V that is more positive vs reversible hydrogen electrode (RHE), a high electron transfer number n (∼3.90), and long-term stability.