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Coronavirus disease 2019 (COVID-19) has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide. Among the infected patients, there is a high prevalence of COVID-19-related cardiovascular injuries. However, the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear. The COVID-19 pandemic also has exacerbated the mental health burden of humans. Considering the close association between neuroimmune interactions and cardiovascular disease, this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease. It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage. Specifically, the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal (HPA) axis, sympathovagal imbalance, and endothelial dysfunction, which lead to an increased risk of developing cardiovascular injury during COVID-19. Therefore, during the prevention and treatment of cardiovascular complications in COVID-19 patients, particular attention should be given to relieve the mental health burden of these patients.

Acute lung injury (ALI) is a common acute respiratory disease with high morbidity and mortality rate in pregnant women. Receptor activator of NF-κB ligand (TNFSF11, also known as RANKL) exerts either pro-inflammatory or anti-inflammatory effects on the immune response. LPS administration reduced the survival time (n = 10, p 0.01), increased wet/dry ratio (n = 10, p 0.001) and lung injury score (n = 10, p 0.001), the elevated proportions of plasmacytoid dendritic cells (pDCs) (n = 10, p 0.0001), tissue-resident DCs (resDCs) (n = 10, p 0.0001), macrophages (n = 10, p 0.0001), and neutrophils (n = 10, p 0.0001), and the expressions of costimulatory molecules and inflammation cytokines (n = 10, p 0.05) in lungs of pregnant mice, compared with non-pregnant mice. In vitro, progesterone up-regulated the expression of RANKL (n 6, p 0.05) on pulmonary fibroblasts. The results of cytokine arrays showed that the cytokines associated with inflammatory response and leukocyte differentiation were decreased in pulmonary fibroblasts after treatment with anti-RANKL neutralizing antibody, compared with control pulmonary fibroblasts. More notably, we found that Tnfsf11

Background: Patients with endometriosis (EMs) have high risks of infertility and spontaneous abortion. How to remodel the fertility of patients with EMs has always been the hot spot and difficulty in the field of reproductive medicine. As an aglycone of ginsenosides, protopanaxadiol (PPD) possesses pleiotropic biological functions and has high medicinal values. We aimed to investigate the effect and potential mechanism of PPD in the treatment of EMs-associated infertility and spontaneous abortion. Methods: The EMs mice models were constructed by allotransplantation. The pregnancy rates, embryo implantation numbers and embryo resorption rates of control and EMs were counted. RNA sequencing, qRT-PCR, enzyme linked immunosorbent assay (ELISA) and FCM analysis were performed to screen and confirm the expression of endometrial receptivity/decidualization-related molecules, inflammation cytokines and NK cell function-related molecules in vitro and/or in vivo. The SWISS Target Prediction, STRING and Cytoscape were carried out to predict the potential cellular sensory proteins, the protein-protein interaction (PPI) network between sensory proteins and fertility-related molecules, respectively. Micro-CT detection, liver and kidney function tests were used to evaluate the safety. Results: Here, we observe that PPD significantly up-regulates endometrial receptivity-related molecules (e.g., Lif, Igfbp1, Mmps, collagens) and restricts pelvic inflammatory response (low levels of IL-12 and IFN-γ) of macrophage, and further remodel and improve the fertility of EMs mice. Additionally, PPD increases the expression of decidualization-related genes and Collagens, and promotes the proliferation, residence, immune tolerance and anagogic functions of decidual NK cells (low levels of CD16 and NKp30, high levels of Ki67, VEGF, TGF-β) in pregnant EMs mice, and further triggers decidualization, decidual NK cell-mediated maternal-fetal immune tolerance and angiogenesis, preventing pregnant EMs mice from miscarriage. Mechanically, these effects should be dependent on ESRs, PGR and other sensory proteins (e.g., AR). Compared with GnRHa (the clinic first-line drug for EMs), PPD does not lead to the decline of serum estrogen and bone loss. Conclusion: These data suggest that PPD prevents EMs-associated infertility and miscarriage in sex hormones receptors-dependent and independent manners possibly, and provides a potential therapeutic strategy with high efficiency and low side effects to remodels the fertility of patients with EMs.

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.

We investigated a custom congenital heart disease (CHD) geneset to assess the diagnostic value of whole-exome sequencing (WES) in karyotype- and copy number variation (CNV)-negative aborted fetuses with conotruncal defects (CTDs), and to explore the impact of postnatal phenotyping on genetic diagnosis.We sequentially analyzed CNV-seq and WES data from 47 CTD fetuses detected by prenatal ultrasonography. Fetuses with either a confirmed aneuploidy or pathogenic CNV were excluded from the WES analyses, which were performed following the American College of Medical Genetics and Genomics recommendations and a custom CHD-geneset. Imaging and autopsy were applied to obtain postnatal phenotypic information about aborted fetuses.CNV-seq identified aneuploidy in 7/47 cases while 13/47 fetuses were CNV-positive. Eighty-five rare deleterious variants in 61 genes (from custom geneset) were identified by WES in the remaining 27 fetuses. Of these, five pathogenic or likely pathogenic variants (PV/LPV) were identified in five fetuses, revealing a 10.6% (5/47) incremental diagnostic yield. Furthermore, RERE:c.2461_2472delGGGATGTGGCGA was reclassified as LPV based on postnatal phenotypic data.We have developed and defined a CHD gene panel that can be utilized in a subset of fetuses with CTDs. We demonstrate the utility of incorporating both prenatal and postnatal phenotypic information may facilitate WES diagnostics.

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.

Aspirin, one of the most widely applied medicines, not only possesses the effects on reducing fever, anti-vascular hyperplasia, and anti-inflammation, but also has the capacity of preventing platelet aggregation. So far, it is acceptable to adopt aspirin, especially low-dose aspirin (LDA), to prevent pregnancy-related complications, such as pregnancy complicated by antiphospholipid syndrome, systemic lupus erythematosus, or preeclampsia; unexplained recurrent spontaneous abortion; fetal growth restriction; and preterm birth. In this article, we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.

A simple and rapid pipette-tip solid-phase extraction (PT-SPE) procedure with derivatization prior to gas chromatography triple quadrupole mass spectrometry analysis is developed for the simultaneous determination of amphetamine (AMP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples. The PT-SPE procedure using self-made sorbent could extract drugs within 6 min from 100-μL urine samples, requiring low solvent-consumption (

The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM. Emerging evidence has shown that collagen and its fragment are expressed at the maternal fetal interface. The regulation of expression of collagen is quite complex, and this process involves a multitude of factors. Collagen exerts a critical role during the successful pregnancy. In addition, the abnormal expressions of collagen and its fragments are associated with certain pathological states associated with pregnancy, including recurrent miscarriage, diabetes mellitus with pregnancy, preeclampsia and so on. In this review, the expression and potential roles of collagen under conditions of physiological and pathological pregnancy are systematically discussed.

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-β led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.

During gestation, excess palmitate (PA) is enriched in decidua. Both excess PA and decidual dysfunctions are associated with numerous adverse pregnancy outcomes such as gestational diabetes, preeclampsia and preterm birth and intrauterine growth restriction. Here, mRNA data about the effects of PA were collected from multiple databases and analyzed. Human decidual tissues were obtained from clinically normal pregnancies, terminated for non-medical reasons, during the first trimester, and decidual stromal cells (DSCs) were isolated and exposed to PA, alone or together with the inhibitors of Toll-like receptor 4 (TLR4), Jun N-terminal kinase (JNK), nuclear factor-kappa-gene binding (NF-kB) or glutamine (GLN) oxidation. Furthermore, DSCs were transfected with lentiviral particles overexpressing human TLR4. We demonstrate that excess PA interacting with its receptor TLR4 disturbs DSC hemostasis during the first trimester. Specifically, high PA signal induced DSC apoptosis and formed an inflammatory program (elevated interleukin-1 beta and decreased interleukin-10) via the activation of TLR4/JNK/NF-kB pathways. A complexed cross-talk was found between TLR4/JNK/NF-kB signals and PA deposition in DSCs. Besides, under an excess PA environment, GLN oxidation was significantly enhanced in DSCs and the suppression of GLN oxidation further augmented PA-mediated DSC apoptosis and inflammatory responses. In conclusion, excess PA induces apoptosis and inflammation in DSCs via the TLR4/JNK/NF-kB pathways, which can be augmented by the suppression of GLN oxidation.

Massive infiltrated and enriched decidual macrophages (dMφ) have been widely regarded as important regulators of maternal-fetal immune tolerance and trophoblast invasion, contributing to normal pregnancy. However, the characteristics of metabolic profile and the underlying mechanism of dMφ residence remain largely unknown. Here, we observe that dMφ display an active glycerophospholipid metabolism. The activation of ENPP2-lysophosphatidic acid (LPA) facilitates the adhesion and retention, and M2 differentiation of dMφ during normal pregnancy. Mechanistically, this process is mediated through activation of the LPA receptors (LPAR1 and PPARG/PPARγ)-DDIT4-macroautophagy/autophagy axis, and further upregulation of multiple adhesion factors (e.g., cadherins and selectins) in a CLDN7 (claudin 7)-dependent manner. Additionally, poor trophoblast invasion and placenta development, and a high ratio of embryo loss are observed in Enpp2(±), lpar1(−/−) or PPARG-blocked pregnant mice. Patients with unexplained spontaneous abortion display insufficient autophagy and cell residence of dMφ. In therapeutic studies, supplementation with LPA or the autophagy inducer rapamycin significantly promotes dMφ autophagy and cell residence, and improves embryo resorption in Enpp2(±) and spontaneous abortion mouse models, which should be dependent on the activation of DDIT4-autophagy-CLDN7-adhesion molecules axis. This observation reveals that inactivation of ENPP2-LPA metabolism and insufficient autophagy of dMφ result in resident obstacle of dMφ and further increase the risk of spontaneous abortion, and provides potential therapeutic strategies to prevent spontaneous abortion. Abbreviations: ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; Atg5: autophagy related 5; ATG13: autophagy related 13; BECN1: beclin 1; CDH1/E-cadherin: cadherin 1; CDH5/VE-cadherin: cadherin 5; CFSE: carboxyfluorescein succinimidyl ester; CLDN7: claudin 7; CSF1/M-CSF: colony stimulating factor 1; CSF2/GM-CSF: colony stimulating factor 2; Ctrl: control; CXCL10/IP-10: chemokine (C-X-C) ligand 10; DDIT4: DNA damage inducible transcript 4; dMφ: decidual macrophage; DSC: decidual stromal cells; ENPP2/ATX: ectonucleotide pyrophosphatase/phosphodiesterase 2; Enpp2(±): Enpp2 heterozygous knockout mouse; ENPP2i/PF-8380: ENPP2 inhibitor; EPCAM: epithelial cell adhesion molecule; ESC: endometrial stromal cells; FGF2/b-FGF: fibroblast growth factor 2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GPCPD1: glycerophosphocholine phosphodiesterase 1; HE: heterozygote; HIF1A: hypoxia inducible factor 1 subunit alpha; HNF4A: hepatocyte nuclear factor 4 alpha; HO: homozygote; ICAM2: intercellular adhesion molecule 2; IL: interleukin; ITGAV/CD51: integrin subunit alpha V; ITGAM/CD11b: integrin subunit alpha M; ITGAX/CD11b: integrin subunit alpha X; ITGB3/CD61: integrin subunit beta 3; KLRB1/NK1.1: killer cell lectin like receptor B1; KRT7/cytokeratin 7: keratin 7; LPA: lysophosphatidic acid; LPAR: lysophosphatidic acid receptor; lpar1(−/−): lpar1 homozygous knockout mouse; LPAR1i/AM966: LPAR1 inhibitor; LY6C: lymphocyte antigen 6 complex, locus C1; LYPLA1: lysophospholipase 1; LYPLA2: lysophospholipase 2; Lyz2: lysozyme 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MARVELD2: MARVEL domain containing 2; 3-MA: 3-methyladenine; MBOAT2: membrane bound O-acyltransferase domain containing 2; MGLL: monoglyceride lipase; MRC1/CD206: mannose receptor C-type 1; MTOR: mechanistic target of rapamycin kinase; NP: normal pregnancy; PDGF: platelet derived growth factor; PLA1A: phospholipase A1 member A; PLA2G4A: phospholipase A2 group IVA; PLPP1: phospholipid phosphatase 1; pMo: peripheral blood monocytes; p-MTOR: phosphorylated MTOR; PPAR: peroxisome proliferator activated receptor; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; PPARGi/GW9662: PPARG inhibitor; PTPRC/CD45: protein tyrosine phosphatase receptor type, C; Rapa: rapamycin; RHEB: Ras homolog, mTORC1 binding; SA: spontaneous abortion; SELE: selectin E; SELL: selectin L; siCLDN7: CLDN7-silenced; STAT: signal transducer and activator of transcription; SQSTM1: sequestosome 1; TJP1: tight junction protein 1; VCAM1: vascular cell adhesion molecule 1; WT: wild type.

Decidualization is an intricate biological process in which extensive remodeling of the endometrium occurs to support the development of an implanting blastocyst. However, the immunometabolic mechanisms underlying this process are still largely unknown. We found that the decidualization process is accompanied by the accumulation of fructose-1,6-bisphosphate (FBP). The combination of FBP with pyruvate kinase M stimulated IL-27 secretion by endometrial stromal cells in an ERK/c-FOS–dependent manner. IL-27 induced decidual COX-2 + M2-like macrophage differentiation, which promotes decidualization, trophoblast invasion, and maternal-fetal tolerance. Transfer of Ptgs2 + /COX-2 + macrophages prevented fetal loss in Il27ra -deleted pregnant mice. FBP levels were low in plasma and decidual tissues of patients with unexplained recurrent spontaneous abortion. In therapeutic studies, FBP supplementation significantly improved embryo loss by up-regulation of IL-27–induced COX-2 + macrophage differentiation in a mouse model of spontaneous abortion. These findings collectively provide a scientific basis for a potential therapeutic strategy to prevent pregnancy loss.

A rapid and sensitive method based on PRiME (process, robustness, improvements, matrix effects, ease of use) pass-through cleanup procedure and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 12 illicit drugs in human plasma was developed and validated. The clover-shaped nano-titania functionalized covalent organic frameworks (CSTF-COFs) has been evaluated in the PRiME pass-through cleanup procedure to remove blood phospholipids from plasma samples. Ion suppression effects can be dramatically reduced by CSTF-COFs based PRiME pass-through cleanup procedure. Under the optimal conditions, the results showed satisfactory recoveries between 85.8% and 109%. Acceptable precision and accuracy were also obtained with RSD values less than 15.0% and RE values below 13.3%. The limits of detections (LODs) of 12 illicit drugs were in the range of 0.018-0.360 µg/L. Furthermore, the PRiME CSTF-COFs cartridge could be conveniently regenerated and reused for 40-50 cycles. The proposed method was applied to real plasma samples from suspected drug abusers, which was proved to be reliable and robust for drug screening in clinical and forensic toxicology.

The effective deployment of an intelligent reflecting mirror array (IRMA) can enhance channel quality and improve the system performance in visible light communications (VLC) systems. This paper focuses on the performance analysis and parameter optimization of an IRMA-aided VLC system. Initially, the channel gains of both line-of-sight (LoS) link and non-LoS links are analyzed. Then, considering the blockage probability of a LoS link, a theoretical expression of the average bit error rate (ABER) is derived. To further improve the system performance, the optimization problems about the parameters of the IRMA are formulated, and schemes are proposed to solve these problems. Moreover, a kind of hardware implementation of the IRMA is provided. Numerical results verify the accuracy of the derived ABER expression and the effectiveness of the proposed schemes.

Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in arachidonic acid (AA) metabolism. COX-2 and its products (prostanoids) serve versatile biological functions during pregnancy. Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells (DICs), particularly in decidual macrophages, corresponding to special gestational phases. This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF1 is expressed at the maternal–fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF1 in DSCs through upregulating the expression of WISP2. Recombinant IGF1 or DSCs-derived IGF1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF1 signaling pathway.

Problem Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown. Methods Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study. Alterations in the numbers of different types of immune cell subsets in the endometrium of patients were analyzed by flow cytometry. Results The present study included 48 patients who were divided into three groups, based on the pathological results: (a) proliferative period (PP, n = 12); (b) simple EH (SEH, n = 30); and (c) complex EH (CEH, n = 6). The results showed that immune cell subpopulations were significantly different between these three groups. Compared with the PP group, the proportion of CD45+ cells and neutrophils and the subtypes of T cells and macrophages were significantly increased in the SEH patients. Compared with the PP and SEH groups, subsets of immunocytes in the CEH group were significantly decreased, including the population of CD45+ cells and the subtypes of T cells and natural killer cells; in contrast, the proportion of macrophages was significantly increased. There were no significant differences between the other cell subsets in each group. Conclusion The changes in immune cell subsets may be closely associated with the progression of EH. Although the specific role of different immune cell subsets in the development of the diseases requires further study, the changes in the proportions of immune cell subsets should not be ignored.

Problem The state of self-renewal and self-maintain of decidual macrophages would be important for immune homeostasis at the maternal-fetal interface. The roles of interleukin (IL)-24 derived from decidual stromal cells (DSCs) on decidual macrophages have not been explored. Method of study IL-24 expression in DSCs was interfered by lentivirus, and the transcription levels of IL-24 in DSCs were verified by real time (RT)-PCR. The levels of IL-24 receptors were determined by flow cytometry assays. The effect of recombination human IL-24 (rhIL-24) on the differentiation and apoptosis of macrophages was analyzed by flow cytometry in vitro. The viability of macrophages was detected by Cell Counting Kit-8 assays. Results The growth of DSCs was not affected obviously only by IL-24 knockdown while the growth of knockdown DSCs was inhibited significantly after co-cultured with decidual macrophages. The levels of IL-24 receptors (IL-20R1 and IL-22R1) were moderately to highly expressed on decidual macrophages and human macrophage cell line U937. The differentiation of decidual macrophages treated by rhIL-24 or co-cultured with IL-24 knockdown DSCs was not affected. Both apoptosis and viability of U937 cells were promoted by rhIL-24. The ratio of Bcl-2/Bax was down-regulated and Ki-67 was up-regulated by IL-24 treatment. The expression of Bcl-2/Bax was up-regulated while Ki-67 was down-regulated in U937 cells after co-cultured by IL-24 knockdown DSCs. Conclusion IL-24 secreted by DSCs promotes the renewal and homeostasis of decidual macrophages possibly via down-regulating the ratio of Bcl-2/Bax and up-regulating of the expression of Ki-67 in early pregnancy.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor. Emerging evidence has shown that CXCL16/CXCR6 is expressed at the maternal-fetal interface, by cell types that include trophoblast cells, decidual stroma cells, and decidual immune cells (eg, monocytes, γδT cells, and natural killer T (NKT) cells). The regulation of expression of CXCL16 is quite complex, and this process involves a multitude of factors. CXCL16 exerts a critical role in the establishment of a successful pregnancy through a series of molecular interactions at the maternal-fetal interface. However, an abnormal expression of CXCL16 is associated with certain pathological states associated with pregnancy, including recurrent miscarriage, pre-eclampsia, and gestational diabetes mellitus (GDM). In the present review, the expression and pleiotropic roles of CXCL16 under conditions of physiological and pathological pregnancy are systematically discussed.

The bond behavior of the interface between carbon fiber reinforced polymer (CFRP) and steel is an important factor affecting the strengthening effect . In this study, the double-shear and single-shear bonded joints were used to research the influences of test methods and epoxy adhesives on the CFRP-steel interfacial behavior. The test parameters included the joint type, adhesive type and adhesive thickness . The failure mode, ultimate load, strain on the CFRP, interfacial shear stress and bond-slip curve were compared. Test results show that the joint type affects the ultimate load, CFRP strain and interfacial shear stress but has no influence on the bond-slip relationship and failure mode. The ultimate loads of the interfaces tested by the double-shear bonded joints are higher than those of the single-shear bonded joints, and the ratio of the ultimate load is determined by the stiffness ratio between the CFRP plate and steel substrate. The adhesive type can affect the failure mode, ultimate load, shapes of the shear stress distribution and bond-slip curve. The ultimate load of the bonded joints with the adhesive A can reach two times that of the joints with the adhesive S. Compared to the specimen with the adhesive S, the specimen with the adhesive A has a lower peak shear stress but much longer stress transfer length. The bond-slip relationships are approximately bilinear and trapezoidal shape, respectively, for the specimens with the adhesives S and A.

Interfacial debonding between fiber-reinforced polymer (FRP) laminate and concrete substrate is one of the critical issues in the externally bonded FRP strengthened concrete members. Existing studies have shown that the addition of liquid rubber into the bonding adhesives can increase debonding resistance of FRP laminate-concrete interface and consequently improve the comprehensive performance of FRP strengthened concrete members under quasi-static loading. The purpose of this study is to clarify the effect of liquid rubber modification on the bond behavior of FRP laminate-concrete interface under dynamic loading. Six groups of double-lap shear specimens with neat or rubber-modified epoxy were tested under static and two dynamic loading rates. The parameters of peak load, FRP strain distribution and interfacial bond stress-slip relationship are analyzed. Test results indicate that the liquid rubber modification can significantly improve the bond capacity of FRP laminate-concrete interface under dynamic loading. Further, the influence mechanism of liquid rubber modification on the dynamic bond behavior of FRP laminate-concrete interface is discussed. Finally, an empirical dynamic bond stress-slip model considering the effect of liquid rubber modification is proposed and validated.

Freeze–thaw (FT) cycling is one of the primary concerns for the application of fiber reinforced polymer (FRP) in cold regions. Existing studies have shown different levels of degradation on the mechanical behavior of carbon FRP (CFRP) or glass FRP (GFRP) and FRP adhesively-bonded joints after FT cycling. This paper presents experimental and numerical studies on the FT durability of basalt FRP (BFRP) single-lap joints (SLJ). BFRP, epoxy resin tensile coupons and BFRP SLJ were prepared and tested before and after FT cycling. Test results indicate that the tensile properties of BFRP and BFRP SLJ are not significantly influenced by FT cycling, while considerable degradation was observed for the epoxy resin and the bond behavior of fiber-to-matrix interface. Numerical simulations were conducted to expand test parameters of the BFRP SLJ before and after FT cycling. Finally, FT durability mechanisms of both BFRP and BFRP SLJ are discussed.

Due to the difficulties and the limitations of traditional measurements, it is extremely challenging to obtain an accurate bond–slip relationship for a fiber-reinforced polymer (FRP) sheets to concrete interface. This paper presents experimental studies aimed at accurately measuring the bond–slip relationship of the FRP sheets to concrete interface using a digital image correlation (DIC) measurement. Double-lap shear specimens were tested with different layers and sequences of carbon or basalt FRP sheets attached to the concrete substrate. The fitting procedures for determining the bond–slip relationship from the DIC results were proposed and validated. The test results show that more comprehensive information during the debonding process can be recorded through the DIC measurement. Error reductions and more accurate bond–slip relationships can be achieved by using the fitting procedures. In addition, the type of FRP sheets and their sequence attached to the concrete surface have a significant influence on the bond behavior between FRP sheets and concrete substrate.

This study presents the results of an experimental investigation of the freeze–thaw (FT) resistance, including the hybridization of fibers, of carbon, basalt and glass fiber-reinforced polymer (CFRP, BFRP and GFRP) sheets commonly used in civil engineering practice. Coupon tests were conducted to investigate the tensile properties of FRP sheets and their corresponding epoxy resins and dry fiber sheets after up to 300 FT cycles. Sustained loading was included in the testing to reflect the behavior of FRP sheets in real structures. The test results indicate that (1) BFRP and hybrid FRP sheets have better FT resistance than CFRP and GFRP sheets, and the hybridization of fibers can contribute to the stability of the tensile properties of these materials after FT exposure; (2) the tensile properties of the resin matrix deteriorate significantly with increasing FT cycles; (3) further degradation of the tensile properties of FRP sheets is caused by sustained loading during FT cycling; and (4) the tensile behavior of dry glass fiber sheets is more sensitive to FT cycling than dry carbon and basalt fiber sheets. Lastly, the degradation mechanism of FRP sheets in FT environments is discussed.

Laribacter hongkongensis is a gram-negative emerging bacterium associated with invasive bacteremic infections in patients with liver disease and fish-borne community-acquired gastroenteritis and traveler's diarrhea. Although the complete genome of L. hongkongensis has been sequenced, no animal model is available for further study of its pathogenicity mechanisms. In this study, we showed that adult zebrafish infected with L. hongkongensis by immersion following dermal abrasion or intraperitoneal injection suffered mortality in a dose-dependent manner, with lethal dose 50 (LD50) of 2.1×10(4) and 1.9×10(4) colony-forming units (CFU)/mL, respectively. All mortalities occurred in the first four days post-infection. Zebrafish that died showed characteristic clinicopathological features: swimming near water surface, marked lethargy and sidestroke; abdominal hemorrhage, ulcers and marked swelling with ascites; and hydropic degeneration and necrosis of hepatocytes around central vein and inflammatory cells infiltration. L. hongkongensis was recovered from the ascitic fluid and tissues of zebrafish that died. Of the 30 zebrafish infected with 2.1×10(4) CFU/mL (LD50) L. hongkongensis isolated from dead zebrafish using the immersion following dermal abrasion method, 18 (60%) died. All zebrafish that died also showed the characteristic clinical and pathological features. Histopathological studies also showed dilation of hepatic central vein and hydropic degeneration. L. hongkongensis was isolated from the zebrafish that died. The Koch's postulates for L. hongkongensis as an infectious agent have been fulfilled. This highly reproducible and effective zebrafish model is of crucial importance for future studies on virulence factors for L. hongkongensis infection.

This paper reports an experimental study on the fatigue behavior of bonded interfaces between carbon fiber reinforced polymer (CFRP) plates and steel plates. A total of 20 single-shear bonded joints were tested under monotonic and fatigue loading. The digital image correlation (DIC) method was employed. The effects of the load ratio, adhesive thickness and adhesive type on the fatigue life were investigated. The failure mode, fatigue life, relative slip, load-slip curve, CFRP strain and interfacial shear stress are presented. The results indicated that the cohesive failure was the dominated failure mode for all specimens. With the increase of the loading cycles, the debond initiated firstly at the loaded end and then propagated gradually toward the free end, which was obviously reflected by CFRP strain and shear stress distributions. The hysteresis was observed in the load-slip curve, indicating the energy dissipation occurred in the interfaces. The fatigue life decreased dramatically with the increase of the load ratio. When the load ratio was the same, the fatigue life decreased with an increasing adhesive thickness, and the fatigue life of the specimen with Sikadur-30 was longer than that with Araldite-2015. However, when the load range was similar, the fatigue life increased with an increase in the adhesive thickness, and the fatigue life of the specimen with Araldite-2015 was longer than that with Sikadur-30. The distribution shapes of the shear stress for two types of the specimens were approximately trapezoidal and triangular under monotonic and fatigue loading.

The influence of adhesive properties on the bond behaviour of externally bonded fibre-reinforced polymer (FRP)-to-concrete joints is the focus of this paper. First, FRP-to-concrete double-lap shear specimens were tested with different types of bonding adhesives. The test results indicate that when softer adhesives are adopted, the peak load, interfacial fracture energy and FRP effective bond length increase while the peak shear stress decreases. Then, a finite element (FE) model including the adhesive layer was proposed to further investigate the influence mechanism of the adhesive properties. A numerical parametric study indicates that the adhesive tensile strength, ultimate strain, elastic modulus and thickness all have varying degrees of impact on the bond behaviour of FRP-to-concrete joints. Finally, a bond-slip model that considers the adhesive elastic modulus is proposed based on experimental and numerical results. To validate this model, a comprehensive test database that includes 128 FRP-to-concrete joints with different adhesives was collected. The proposed model has been shown to have a higher accuracy and lower dispersion than the existing models for the prediction of the peak loads of FRP-to-concrete joints with different adhesives.

This paper presents an experimental investigation on the bond behavior between basalt fiber–reinforced polymer (BFRP) sheet and concrete substrate under the coupled effects of freeze-thaw cycling and sustained load. Test variables were freeze-thaw cycles, level of sustained load, and adhesive type. Double-lap shear specimens were used in the tests, and a specially designed reaction-loading system was used to apply the sustained load during freeze-thaw cycles. Specimens with or without sustained load were exposed to up to 300 freeze-thaw cycles. A modified epoxy resin, made by adding a toughening agent to the original epoxy resin, was used in the test to study the effect of adhesive type on the durability of the BFRP–concrete interface. Coupon tests were also conducted to determine the freeze-thaw resistance of the constituent materials of the BFRP–concrete interface. After exposure, double-lap shear tests were carried out to investigate the residual bond capacity of the BFRP–concrete interface. Di...

The impact performance of PE can be greatly enhanced by the use of functionalized conch powder, while maintaining high tensile strength thus giving this study high potentiality for its practical applications. The conch powder was treated by titanate coupling agent NDZ-201 before use and the influence of different proportions of conch powder on the mechanical properties of PE/conch powder composite is discussed in this article. The impact strength has a maximum value of 63.4kJ/m2 and the frictional loss records a minimum of 4.27×10-1mm3/(Nm)-1 and 42.2% lower than that of pure PE.

This study focuses on the tensile behavior of fiber-reinforced polymer (FRP) composites in a concrete-based alkaline environment. Because basalt/glass FRP (BFRP/GFRP) composites exhibit relatively poor alkaline resistance compared with carbon FRP (CFRP) composites, a rubber toughening modification method has been proposed to mitigate microcracking and decrease the diffusion of the alkaline solution in the resin matrix. Different proportions of liquid rubber toughening agents were added into the epoxy resin, on the basis of which different FRP composites were made and then subjected to tensile tests after alkaline exposure. Test results indicated that the rubber toughening modification approach can significantly reduce the tensile strength degradation of the BFRP and GFRP composites in the alkaline solution. Moreover, no degradation of the elastic modulus for the FRP composites was observed. The weight gain and microstructure of the FRP composites were also investigated before and after the alkaline exposure to determine the corrosion mechanisms of the FRP composites in the alkaline environment and interpret the mechanical test results.

In this paper, a novel and recyclable amino-functionalized nano-composite material (NCM) using tetraethylenepentamine (TEPA) as a coupling agent was synthesized. The properties of the TEPA-NCM were characterized by transmission electron microscopy (TEM), Fourier transform infrared analysis (FTIR), thermogravimetric analysis (TGA) and elemental analysis (EA). An effective dispersive solid-phase extraction (dSPE) procedure using the TEPA-NCM was developed, and comparative studies were carried out among Carbon/NH2 SPE, primary secondary amine (PSA) dSPE and TEPA-NCM dSPE. The results showed that TEPA-NCM dSPE was faster, easier and more effective to clean and enrich than the Carbon/NH2 cartridges, and the TEPA-NCM was much more effective to remove the pigments in vegetable samples than the PSA materials. The TEPA-NCM could be reused at least five times without much sacrifice of the cleanup efficiency. Furthermore, a gas chromatography–triple quadrupole mass spectrometry (GC–QqQ-MS/MS) method was established for the simultaneous determination of 29 pesticides (such as organochlorine and organophosphorus pesticides) in vegetables by dSPE using acetonitrile as an extraction solvent and TEPA-NCM as an adsorbent instead of PSA. The recoveries were in the range of 75–114% for all analytes except for trans-chlordane. The RSDs were in the range of 2–17%. The linearities were in the range of 0.4–100.0 μg/kg with determination coefficients (r2) higher than 0.986 for all compounds. The limits of detection (LODs) for all pesticides were less than 0.29 μg/kg and the limits of quantification (LOQs) were between 0.17 and 0.95 μg/kg. The developed method was applied to fifteen real vegetable samples, and it was confirmed that the TEPA-NCM was one of a kind of highly effective dSPE materials used for the pesticides analyses.

Coupon tests were conducted to investigate the mechanical characteristics of basalt FRP (BFRP) sheet, basalt-carbon hybrid FRP sheets and the corresponding epoxy rein under the effect of freeze-thaw cycling. FRP sheets and epoxy rein coupons were subjected to up to 200 and 250 freeze-thaw cycles respectively. Test parameters included the number of freeze-thaw cycles and the types of FRP composites. Test results show that (1) BFRP sheet perform better than CFRP or GFRP sheets under high freeze-thaw cycles; (2) exposed hybrid FRP sheets not only show very little loss in mechanical properties, but also contribute to the stability of test data; (3) mechanical properties of rein epoxy decrease significantly with increasing freeze-thaw cycles.