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In mammals, DYRK2 increases p53 phosphorylation level by interacting with it and then promotes cell apoptosis. However, the function of fish DYRK2 has not yet been elucidated. In this paper, we cloned and identified the coding sequence (CDS) of a grass carp DYRK2 (CiDYRK2) which is 1773 bp in length and encodes 590 amino acids. SMART predictive analysis showed that CiDYRK2 possesses a serine/threonine kinase domain. Subsequently, we used the dsRNA analog polyinosinic-polycytidylic acid (poly (I:C) and Grass carp reovirus (GCRV) to stimulate grass carp and CIK cells for different times and found that CiDYRK2 mRNA was significantly up-regulated both in fish tissues and cells. To explore the function of CiDYRK2, we carried out overexpression and knockdown experiments of CiDYRK2 in CIK cells. Real-time quantitative PCR (Q-PCR), TdT-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry were used to detect the ratio of BAX/BCL-2 mRNA, the number of TUNEL positive cells, the proportion of Annexin V-positive cells respectively. The results showed that CiDYRK2 significantly up-regulated BAX/Bcl-2 mRNA ratio and increased the number of TUNEL-positive cells, as well as the proportion of Annexin V-positive cells. On the contrary, knock-down of CiDYRK2 significantly down-regulated BAX/Bcl-2 mRNA ratio in the cells. Therefore, CiDYRK2 promoted cell apoptosis. To study the molecular mechanism by which CiDYRK2 promoting cell apoptosis, subcellular localization and immunoprecipitation experiments were used to study the relationship between grass carp DYRK2 and the pro-apoptotic protein p53. The results showed that CiDYRK2 and Cip53 were located and co-localized in the nucleus. Co-immunoprecipitation experiment also showed that CiDYRK2 and Cip53 can bind with each other. We further found that DYRK2 can increase the phosphorylation level of p53. In a word, our results showed that grass carp DYRK2 induces cell apoptosis by increasing the phosphorylation level of p53. • The expression of CiDYRK2 was up-regulated by GCRV and poly (I:C) stimulation. • CiDYRK2 can physically bind to Cip53. • CiDYRK2 promoted apoptosis by increasing the phosphorylation level of p53. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs), a subclass of non-coding RNAs characterized by covalently closed continuous loops, play a key role in tumorigenesis and aggressiveness. However, the potential molecular mechanism of circRNAs in triple-negative breast cancer (TNBC) remains largely unknown. Exploring their roles and mechanisms in TNBC progression may help identify new diagnostic markers and therapeutic targets. In this study, we found that circ-FOXO3 was dramatically downregulated in TNBC tissues and blood samples from patients with TNBC. Notably, low circ-FOXO3 expression in TNBC tissues and bloods was associated with lymph node metastasis and unfavorable outcomes in patients with TNBC. Overexpression of circ-FOXO3 significantly inhibited the growth, invasion, and metastasis of TNBC cells both in vitro and in vivo. Moreover, we demonstrated that circ-FOXO3 was predominantly expressed in the cytoplasm and directly interacted with Wolf-Hirschhorn syndrome candidate 1 (WHSC1), thereby inhibiting WHSC1 nuclear localization and activity, resulting in the inhibition of H3K36me2 modifications at the Zeb2 promoter, ultimately inhibiting Zeb2 expression and halting TNBC growth and metastasis. Taken together, these results reveal the tumor-suppressive functions of circ-FOXO3 in inhibiting WHSC1-mediated H3K36me2 modification of Zeb2, suggesting that circ-FOXO3 could serve as a potential novel predictive prognostic biomarker and therapeutic target for TNBC. • Circ-FOXO3 expression is downregulated in TNBC tissues and cells. • Circ-FOXO3 suppresses TNBC cell proliferation and metastasis via Zeb2 inhibition. • Circ-FOXO3 inhibits TNBC progression by interacting with WHSC1 and inhibiting the WHSC1-H3K36me2-Zeb2 signaling pathway. [ABSTRACT FROM AUTHOR]

• P7C3-A20 could decrease brain atrophy and alleviate apoptosis after HI injury. • P7C3-A20 could improve the prognosis after HI injury. • P7C3-A20 has not been found toxic effects on other organs of newborn rats. • P7C3-A20 exerted neuroprotection via the PI3K/ Akt/GSK3β pathway. Hypoxic–ischemic encephalopathy (HIE) in neonates can lead to severe long-term disabilities including cerebral palsy and brain injury. The small molecule P7C3-A20 has been shown to exert neuroprotective effects in various disorders such as ischemic stroke and neurodegenerative diseases. However, it is unclear whether P7C3-A20 has therapeutic potential for the treatment of HIE, and the relationship between P7C3-A20 and neuronal apoptosis is unknown. To address these questions, the present study investigated whether P7C3-A20 reduces HI injury in vitro using a PC12 cell oxygen-glucose deprivation (OGD) model and in vivo in postnatal day 7 and 14 rats subjected to HI, along with the underlying mechanisms. We found that treatment with P7C3-A20 (40–100 µM) alleviated OGD-induced apoptosis in PC12 cells. In HI model rats, treatment with 5 or 10 mg/kg P7C3-A20 reduced infarct volume; reversed cell loss in the cortex and hippocampus and improved motor function without causing neurotoxicity. The neuroprotective effects were abrogated by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results demonstrate that P7C3-A20 exerts neuroprotection by activating PI3K/protein kinase B/glycogen synthase kinase 3β signaling and can potentially be used to prevent brain injury in neonates following HIE. [ABSTRACT FROM AUTHOR]

The involvement of the tumor stromal cells in acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism remains unclear. In the present study, we investigated the role and mechanism underlying Cancer-associated fibroblasts (CAFs) in TKI resistance of NSCLCs. In vitro and in vivo experiments showed that HCC827 and PC9 cells, non-small cell lung cancer cells with EGFR-activating mutations, became resistant to the EGFR-TKI gefitinib when cultured with CAFs isolated from NSCLC tissues. Moreover, we showed that CAFs could induce epithelial-mesenchymal transition (EMT) phenotype of HCC827 and PC9 cells, with an associated change in the expression of epithelial to mesenchymal transition markers. Using proteomics-based method, we identified that CAFs significantly increased the expression of the Annexin A2 (ANXA2). More importantly, knockdown of ANXA2 completely reversed EMT phenotype and gefitinib resistance induced by CAFs. Furthermore, we found that CAFs increased the expression and phosphorylation of ANXA2 by secretion of growth factors HGF and IGF-1 and by activation of the corresponding receptors c-met and IGF-1R. Dual inhibition of HGF/c-met and IGF-1/IGF-1R pathways could significantly suppress ANXA2, and markedly reduced CAFs-induced EMT and gefitinib resistance. Taken together, these findings indicate that CAFs promote EGFR-TKIs resistance through HGF/IGF-1/ANXA2/EMT signaling and may be an ideal therapeutic target in NSCLCs with EGFR-activating mutations. [ABSTRACT FROM AUTHOR]

• The countercurrent flow limitation (CCFL) of vertical pipes was experimentally studied. • The effects of pipe diameter and pipe length on the CCFL were determined by experiment. • The existing CCFL correlation models were examined based on the experimental result. • A novel dimensionless group (Ku k 0.5μ k *0.1) was proposed for correlating diameter effect. • A new correlation predicting the diameter and length effects accurately was advanced. The gas–liquid two-phase countercurrent flow limitation (CCFL) of vertical pipes is an important subject of concern in various industries. Predicting the CCFL of vertical pipes, i.e. the flow rate relationship between the gas and liquid phases under CCFL conditions, has not yet been clearly determined on effects of the structural parameters of the pipe. In this study, a visualization experiment on the CCFL of vertical pipes was performed by using air and water as the two phases. The effects of pipe diameter and pipe length were tested in the ranges of 25–100 mm and 0.50–2.0 m, respectively. Based on the experimental result, the flow behaviors of the CCFL in vertical pipes were analyzed, and four existing CCFL correlation models were examined in their capabilities to correlate the effects of pipe diameter and pipe length. The result shows that the flow patterns in vertical pipes are essentially annular flows and annular-mist flows under CCFL conditions, and the flow behaviors on gas–liquid interface present different features as the pipe differed in diameters. Examination of the available CCFL models indicates that none of them has reached a satisfactory correlation on the effects of pipe diameter and pipe length. Consequently, based on a reasonable fluid mechanics analysis, a novel CCFL correlation model that can correlate the effects of pipe diameter and pipe length was advanced. This model provides a reasonable and accurate prediction of the CCFL of vertical pipes when the pipe varies in structural parameters, which is of great significance to the safe and efficient operation of the related equipment in nuclear power generation, natural gas extraction and chemical industries. [ABSTRACT FROM AUTHOR]

Defects in decidual response are associated with adverse pregnancy outcomes which includes recurrent pregnancy loss (RPL). It is reported that cellular senescence happens during decidualization and pro-senescent decidual response in the luteal phase endometrium is related to RPL. However, the underlying mechanisms of how excessive decidual senescence takes place in RPL decidua cells remain largely unexplored. The senescent phenotype of RPL decidua and tumor necrosis factor receptor 1(TNFR1) expression were analyzed by using our previously published single-cell sequencing dataset of decidua cells from 6 RPL and 5 matched normal decidua, which were further verified by PCR and WB in decidual tissues. Effects of TNFα on the decidual stromal cells (DSCs) senescence and underlying molecular pathways were analyzed using the in vitro decidualization model of human endometrial stromal cells (HESCs). We showed that decidual stroma cells from RPL patients exhibited transcriptomic features of cellular senescence by analysis of single-cell datasets. The TNFα level and TNFR1 expression were increased in RPL decidua tissues. Furthermore, in vitro cell model demonstrated that increased TNFα induced excessive senescence during decidualization and TNFR1/p53/p16 pathway mediates TNFα-induced stromal senescence. In addition, we also found that the expression of IGFBP1 was regulated by TNFα-TNFR1 interaction during decidualization. Taken together, the present findings suggest that the increased secretion of TNFα induced stromal cell excessive senescence in RPL decidua, which is mediated via TNFR1, and thus provide a possible therapeutic target for the treatment of RPL. • Decidual stroma cells from RPL patients exhibited transcriptomic features of cellular senescence. • Low-dose TNFα induced excessive senescence in human endometrial stromal cells. • TNFR1/P53 pathway mediates TNFα-induced stromal senescence. • Increased secretion of TNFα induced stromal cell senescence in RPL decidua, which is mediated via TNFR1. [ABSTRACT FROM AUTHOR]

Direct analysis in real time mass spectrometry (DART-MS) provides a new analytical method for traditional Chinese medicine (TCM). The present study investigated the effects of key ion source operating parameters on DART-MS analysis of various TCM active components. A total of 18 active components, including phenylpropanoids, alkaloids, saponins, flavones, volatile oils, and glycosides, were examined. For each substance, the peak area and signal-to-noise of its characteristic ions under different reagent gases and heater temperatures were compared. Based on the comparison, the relationships among chemical structures, ion source parameters and instrument responses were revealed. Finally, some suggestions about choosing reagent gas and heater temperature were proposed for types of TCM active substance, which offered a reference for the application of DART-MS on TCM analysis. [ABSTRACT FROM AUTHOR]

Electrochemical synthesis in-situ of hydrogen peroxide (H 2 O 2) is an alternative to the anthraquinone oxidation (AO) process. The catalyst with high performance and excellent stability is the key part of oxygen reduction reaction (ORR). Fluorine (F) has high electronegativity, which can induce the polarization of adjacent carbon, produce active centers and increase the force between oxygen and carbon. In this work, we used a simple synthesis method to prepare F-doped carbon electrocatalyst in F 2 atmosphere. The F-doped carbon as cathode was used to generate H 2 O 2 via the two-electron pathway. The H 2 O 2 concentration and selectivity of catalyst can reach 2837.5 mg L−1 and 95.7% after electrolyzing three hours, respectively. The linear sweep voltammetry shows that the onset potential of F-doped carbon is 37 mV more positive than that of pristine carbon, and its limited current density of catalyst reach 5.882 mA cm−2. The density functional theory (DFT) calculation demonstrates the covalent bonds CF 2 can activate O 2 and promote desorption of intermediate OOH to enhance H 2 O 2 production. The prepared F-doped carbon with excellent performance and outstanding cycle durability is a promising electrocatalyst. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] DART-MS was proposed as a PAT tool for real-time monitoring of percolation process. [•] MPLS model was established to detect and diagnose the batch variations. [•] Process faults were explained by variable contributions of effective compositions. [•] DART-MS was proven to be a potential PAT tool for samples in complex matrices. [Copyright &y& Elsevier]

Abstract: A surface flowing mode sample holder was designed as an alternative sampling strategy for direct analysis in real time mass spectrometry (DART-MS). With the sample holder, the on-line coupling of macroporous resin column chromatography with DART-MS was explored and the new system was employed to monitor the column chromatography elution process of Panax notoginseng. The effluent from macroporous resin column was first diluted and mixed with a derivatization reagent on-line, and the mixture was then directly transferred into the ionization region of DART-MS by the sample holder. Notoginsenosides were methylated and ionized in a metastable helium gas stream, and was introduced into MS for detection. The on-line system showed reasonable repeatability with a relative standard deviation of 12.3% for the peak area. Three notoginsenosides, i.e. notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1, were simultaneously determined during the eluting process. The alteration of the chemical composition in the effluent was accurately identified in 9min, agreeing well with the off-line analysis. The presented technique is more convenient compared to the traditional UPLC method. These results suggest that the surface flowing mode DART-MS has a good potential for the on-line process monitoring in the pharmaceutical industry. [Copyright &y& Elsevier]

An activity-based approach to optimize the ultrasonic-assisted extraction of antioxidants from Pericarpium Citri Reticulatae ( Chenpi in Chinese) was developed. Response surface optimization based on a quantitative composition-activity relationship model showed the relationships among product chemical composition, antioxidant activity of extract, and parameters of extraction process. Three parameters of ultrasonic-assisted extraction, including the ethanol/water ratio, Chenpi amount, and alkaline amount, were investigated to give optimum extraction conditions for antioxidants of Chenpi: ethanol/water 70:30 v/v, Chenpi amount of 10 g, and alkaline amount of 28 mg. The experimental antioxidant yield under the optimum conditions was found to be 196.5 mg/g Chenpi, and the antioxidant activity was 2023.8 μmol Trolox equivalents/g of the Chenpi powder. The results agreed well with the second-order polynomial regression model. This presented approach promised great application potentials in both food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Abstract: Batch-to-batch variability of traditional Chinese medicine (TCM) has already heavily limited its industrial development. By utilizing direct analysis in real time mass spectrometry (DART-MS) and multivariate statistical analysis, the present study introduced a novel and rapid methodology for TCM manufacturing process monitoring. Danshen alkaline precipitation was employed as an example operating unit to demonstrate the effectiveness of this new technique. A total of 15 batches run under normal operating conditions were used to develop a reference principal component analysis model and then enabled the establishment of multivariate control charts. Hotteling T 2 and DModX charts were applied to examine batch-to-batch reproducibility of 12 test batches. Artificial variations including starting material change and process fault were identified, which was in a good agreement with conventional analysis result. Further understanding of the deviating process behavior was achieved by investigating the contribution plot of abnormal batches. The results showed that DART-MS, in conjunction with multivariate analysis, provided valuable information on model process and gave us a new perspective for TCM manufacturing process monitoring. [Copyright &y& Elsevier]

Abstract: The paper presents a novel strategy to identify analytical markers of traditional Chinese medicine preparation (TCMP) rapidly via direct analysis in real time mass spectrometry (DART-MS). A commonly used TCMP, Danshen injection, was employed as a model. The optimal analysis conditions were achieved by measuring the contribution of various experimental parameters to the mass spectra. Salvianolic acids and saccharides were simultaneously determined within a single 1-min DART-MS run. Furthermore, spectra of Danshen injections supplied by five manufacturers were processed with principal component analysis (PCA). Obvious clustering was observed in the PCA score plot, and candidate markers were recognized from the contribution plots of PCA. The suitability of potential markers was then confirmed by contrasting with the results of traditional analysis methods. Using this strategy, fructose, glucose, sucrose, protocatechuic aldehyde and salvianolic acid A were rapidly identified as the markers of Danshen injections. The combination of DART-MS with PCA provides a reliable approach to the identification of analytical markers for quality control of TCMP. [Copyright &y& Elsevier]

Abstract: Salvianolic acid A was subjected to thermal degradation condition in distilled water at 90°C. Four degradation products, including two novel compounds (1, 2) and two known ones (5, 6), were isolated by reverse-phase semi-preparative liquid chromatography and identified on the basis of NMR and MS data. Other two degradation products (3, 4) were determined by LC-MS analysis. [Copyright &y& Elsevier]

Objectives: Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including recurrent spontaneous abortion (RSA). The role of cell heterogeneity of maternal decidua in RSA is yet to be illustrated. Materials and methods: A total of 66,078 single cells from decidua samples isolated from patients with RSA and healthy controls were analysed by unbiased single‐cell RNA sequencing (scRNA‐seq). Results: Our scRNA‐seq results revealed that stromal cells are the most abundant cell type in decidua during early pregnancy. RSA samples are accompanied by aberrant decidualization and obviously obstructed communication between stromal cells and other cell types, such as abnormal activation of macrophages and NK cells. In addition, the over‐activated TNF superfamily member 12 (TNFSF12, TWEAK) and FASLG in RSA are closely related to stromal cell demise and pregnancy failure. Conclusions: Our research reveals that the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention. [ABSTRACT FROM AUTHOR]

The impact of autoclaving or autoclave-debranching treatments on the multi-scale structure of resistant starch (RS) and the relationship with starch digestion remains unclear, despite their widespread use in its preparation. This work investigated the relationship between RS structure in black Tartary buckwheat and its digestibility by analyzing the effects of autoclaving and autoclave-debranching combined treatments on the multi-scale structure of RS. The results showed that black Tartary buckwheat RS exhibited a more extensive honeycomb-like network structure and enhanced thermal stability than either black Tartary buckwheat native starch (BTBNS) or common buckwheat native starch (CBNS). Autoclaving and autoclaving-debranching converted A-type native starch to V-type and possibly the formation of flavonoid-starch complexes. Autoclaving treatment significantly increased the proportion of short A chain (DP 6-12) and the amylose (AM) content, reduced the viscosity and the total crystallinity. Notably, the autoclave-debranching co-treatment significantly enhanced the resistance of starch to digestion, promoted the formation of perfect microcrystallines, and increased the AM content, short-range ordered degree, and the proportion of long B2 chain (DP 25-36). This study reveals the relationship between the multi-scale structure and digestibility of black Tartary buckwheat RS by autoclaving combined with debranching modification. [ABSTRACT FROM AUTHOR]

Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purβ. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purβ, and highlight the clinical implications of these mechanisms in the pathology of RSA. JAZF1 regulates human endometrial stromal cells survival and decidualization by restricting the activity of Purβ, which induces the expression of G0S2, a factor that is involved in the mitochondrial apoptotic pathway in recurrent spontaneous abortion. [ABSTRACT FROM AUTHOR]

SiC/multi-walled carbon nanotube (MWCNT) composites are considered to be promising materials for high-temperature electromagnetic wave (EMW) absorption due to their strong thermal stability and tunable dielectric properties. However, the EMW absorption performance of these composites is limited by poor impedance matching. This study proposes a novel multiscale structure synergistic regulation approach to enhance EMW absorption performance, which involves constructing a heterointerface structure and a triple periodic minimal surface (TPMS) meta-structure. The addition of a SiO 2 shell as an impedance layer to the SiC/MWCNT core to improve the intrinsic impedance. Meanwhile, the heterointerface between the core-shell structure leads to multiple interface polarization, significantly enhancing EMW energy dissipation. Consequently, the effective absorption bandwidth (EAB) of SiO 2 –SiC/MWCNT composites increased from 0.88 to 4.56 GHz. Furthermore, a TPMS meta-structure, fabricated by three-dimensional (3D) printing and sol infiltration technology, is developed to further improve impedance matching with the equivalent electromagnetic effect. Simulation and experimental results demonstrate that the SiO 2 –SiC/MWCNT TPMS meta-structure exhibits broadband EMW absorption performance, with the EAB reaching 7.2 GHz. This improvement is attributed to the synergistic regulation of the heterointerface structure and TPMS meta-structure, which provides a good balance between the requirements of electromagnetic loss and impedance matching. Additionally, the composites exhibit excellent oxidation resistance, as their EAB remains almost unchanged after exposure to 1000 °C for 6 h. This research offers a new design paradigm for ultrabroadband design of the nonmagnetic high-temperature absorbing materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The cesarean delivery (CD) rate has been increasing globally. Trial of labor after cesarean delivery (TOLAC) has been used as a key method for the reduction of the CD rate. Little is known, however, about the association between the second-stage duration of TOLAC and adverse maternal and neonatal outcomes. This study evaluated the association between perinatal outcomes and the duration of second-stage labor in women undergoing TOLAC.Methods: A 10-year retrospective cohort study was performed at the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2010 and January 2020. Women undergoing TOLAC who reached the second stage of labor were included in this study. Duration of the second stage of labor was examined as a categorical variable (group I: <0.5 h, group II: 0.5-2 h and group III: ≥2 h) and as a continuous variable to evaluate the association with adverse perinatal outcomes by using multivariable regression models and a Cox proportional hazards regression model adjusting for potential confounders.Results: Of the 1,174 women who met the inclusion criteria, the median (interquartile range) length of the second stage was 0.5 h (0.3-0.9 h). Among them, 1,143 (97.4%) delivered vaginally and 31 underwent an unplanned CD. As the second-stage duration increased, operative vaginal delivery (OVD), CD, and postpartum hemorrhage (PPH) rates increased. Women in group III had higher risks of OVD (aOR = 11.34; 95% CI [5.06-25.41]), CD (aOR = 4.22; 95% CI [1.32-13.43]), and PPH (aOR = 2.43; 95% CI [1.31-4.50]) compared with group I. Correspondingly, blood loss and the oxytocin used to treat PPH increased significantly, while the postpartum hemoglobin reduced significantly in group III compared with group I. The incidence of uterine rupture, uterine atony, cervical laceration, red blood cell transfusion, and intensive care unit admission were similar in all three groups. Neonatal outcomes were not affected by the second-stage duration.Conclusions: Women undergoing TOLAC with second-stage duration of ≥2 h have higher odds of OVD, unplanned intrapartum CD, and PPH. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis and limited treatment. As a major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating the aggressive behavior of TNBC. This study aimed to explore the novel mechanism of TAMs in the regulation of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties in TNBC. Methods: Expression of the M2-like macrophage marker CD163 was evaluated by immunohistochemistry in human breast cancer tissues. The phenotype of M2 macrophages polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells was verified by flow cytometry. Transwell assays, wound healing assays, western blotting, flow cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene assays, and immunofluorescence assays were conducted to investigate the mechanism by which TAMs regulate EMT and CSC properties in BT549 and HCC1937 cells. Results: Clinically, we observed a high infiltration of M2-like tumor-associated macrophages in TNBC tissues and confirmed that TAMs were associated with unfavorable prognosis in TNBC patients. Moreover, we found that conditioned medium from M2 macrophages (M2-CM) markedly promoted EMT and CSC properties in BT549 and HCC1937 cells. Mechanistically, we demonstrated that chemokine (C–C motif) ligand 2 (CCL2) secretion by TAMs activated Akt signaling, which in turn increased the expression and nuclear localization of β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced EMT and CSC properties. Conclusions: This study provides a novel mechanism by which TAMs promote EMT and enhance CSC properties in TNBC via activation of CCL2/AKT/β-catenin signaling, which may offer new strategies for the diagnosis and treatment of TNBC. 5r3JY8ktnQBgogUH1DXeQZ Video Abstract [ABSTRACT FROM AUTHOR]

Objectives: The impacts of the current COVID‐19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS‐CoV‐2 infection at early‐to‐mid gestation on maternal and foetal health remains unclear. Materials and methods: Here, we report the follow‐up study of a pregnant woman of her whole infective course of SARS‐CoV‐2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single‐cell RNA sequencing (scRNA‐seq) for the placenta were performed. Results: Compared with the gestational age‐matched control placentas, the placenta from this COVID‐19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast‐related genes. The scRNA‐seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over‐activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood. Conclusion: These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal–foetal interface that may be attributed to SARS‐CoV‐2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID‐19. [ABSTRACT FROM AUTHOR]

A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant ( P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Protein inhibitor of activated signal transducer and activator of transcription (PIAS) family protein involved in gene transcriptional regulation acts as negative regulator in Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. But until now, the roles of PIAS in fish are not clear. In this study, we identified the two mammalian PIAS1 orthologs from Ctenopharyngodon idellus , namely CiPIAS1a and CiPIAS1b , respectively. They can respond to the stimulation from Polyribocytidylic acid (Poly I:C), Grass Carp Reovirus (GCRV) and Lipopolysaccharides (LPS) respectively, so we suggested that they could participate in interferon (IFN)-mediated antiviral and antibacterial immune response. The subcellular localization and nuclear cytoplasm extraction showed that CiPIAS1a and CiPIAS1b were mainly distributed in the nucleus. In addition, Co-IP showed that they separately inhibited the phosphorylation of STAT1 via interacting with it, which leads to the reduction of IFN1 expression. • CiPIAS1a and CiPIAS1b were identified in grass carp. • CiPIAS1a and CiPIAS1b responded to GCRV, Poly I:C and LPS stimulation respectively. • CiPIAS1a and CiPIAS1b separately interacted with CiSTAT1. • CiPIAS1a and CiPIAS1b reduced the expression of CiIFN1 through inhibiting phosphorylation of CiSTAT1, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Through this study, we aimed to evaluate the effects of different types of placenta previa (PP) on maternal and neonatal outcomes. Methods: This study was conducted in The Third Affiliated Hospital of Guangzhou Medical University and Tongji Hospital between January 2009 and 2019. PP was traditionally classified into four types, namely low-lying placenta, marginal, partial, and complete PP. Previous studies have classified PP into two types, namely low-lying placenta and PP. Based on our clinical experience, we proposed the classification of PP into three types, for the first time, which included low-lying placenta, "marpartial" (marginal and partial) PP, and complete PP. Multivariate logistic regression analysis was performed to determine the effects of different types of PP on maternal and neonatal outcomes. Results: In total, 4490 singleton pregnancies were complicated with PP. In the four-classification method, compared with women with low-lying placenta, women with complete PP had a risk of placenta accrete spectrum disorders, postpartum hemorrhage (PPH), hemorrhagic shock, severe PPH, blood transfusion, hysterectomy, puerperal infection, preterm labor, NICU admission, and low birth weight. There was no difference in maternal and neonatal outcomes between marginal and partial PP, except for increased chances of preterm labor and low birth weight in partial PP. In the two-classification method, PP was the risk factor for most of the adverse maternal and neonatal outcomes, compared with low-lying placenta. Conclusion: Complete PP and low-lying placenta were associated with the highest and lowest risks of adverse pregnancy outcomes, respectively, whereas clinically similar outcomes were observed between marginal and partial PP. The three-classification of PP may be practical from the clinical perspective. [ABSTRACT FROM AUTHOR]

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician. [ABSTRACT FROM AUTHOR]

Background: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean.Methods: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis.Results: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years).Conclusions: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated. [ABSTRACT FROM AUTHOR]

[Display omitted] • Near defect-free and defect-rich UiO-66-type MOFs were successfully prepared. • Affecting mechanism of defects on CO 2 capture performance was elucidated. • Importance of thermal treatment for CO 2 capture performance was illustrated. • Necessity of identifying local fine structure for CO 2 capture evaluation was noted. Carbon capture and storage (CCS) technology is currently an essential response to the global warming problem caused by excessive CO 2 emissions. Efficient and reproducible adsorbents for flue gas treatment play an important role in CCS technology, and metal–organic frameworks (MOFs) are considered to be ideal candidates by virtue of their designable CO 2 sorption sites. However, carbon capture performance evaluation and reproducibility of MOFs still hinder their application promotion in industrial production. In this work, an extended UiO-66-type MOF based on 1,4-naphthalenedicarboxylate, was successfully synthesized in both a near defect-free form (UiO-66N) and a defect-rich form (DUiO-66N), for exploring the influence of crystalline defects and thermal treatments on carbon capture performance. Although powder X-ray diffraction showed that UiO-66N and DUiO-66N possessed the same crystalline phase, transmission electron microscopy, thermalgravimetric analyse and gas/dye sorption confirmed the presence of crystalline defects and the variation of porosity in DUiO-66N. CO 2 sorption isotherms and flue gas breakthrough experiments revealed the defect-induced improved carbon capture performance, which was also supported by density functional theory. Meanwhile, the metastability of defects required low thermal treatment temperatures for activation and regeneration thus maintaining the superior carbon capture performance. These findings suggested that in reproducing and evaluating the carbon capture performance of MOFs, it cannot rely only on the global crystalline phase judgment, but needs to identify the local fine structure as well as optimize activation and regeneration conditions. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown that fibroblast growth factor 21 (FGF21) has a potential neuroprotective effect against brain injury. However, the effect of FGF21 on neonatal HI brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether recombinant human FGF21 (rhFGF21) could exert a neuroprotective effect after HI and explore the associated mechanism. The results showed that the rhFGF21 treatment remarkably reduced the infarct volume, ameliorated the body weight and improved the tissue structure after HI in neonatal rats. In addition, the rhFGF21 treatment lengthened the running endurance times in the rotarod test and decreased the mean escape latencies and increased the number of platform crossings in the Morris water maze test at 21 d post-HI insult. In contrast, the FGFR1 inhibitor PD173074 and PI3K inhibitor LY294002 partially reversed these therapeutic effects. In isolated primary cortical neurons, the rhFGF21 treatment protected primary neurons from oxygen-glucose deprivation (OGD) insult by inhibiting neuronal apoptosis and promoting neuronal survival. Both our in vivo and in vitro results reveal that rhFGF21 could inhibit neuronal apoptosis by activating the PI3K/Akt signaling pathway via FGF21/FGFR1/β-klotho complex formation. Therefore, rhFGF21 may be a promising therapeutic agent for promoting functional recovery after HI-induced neonatal brain injury. • rhFGF21 reduces the brain infarct volume and ameliorates the histological structure. • rhFGF21 improves motor and learning disabilities in rats after hypoxia-ischemia. • rhFGF21 activates the PI3K/Akt pathway via FGFR1/β-klotho post hypoxia-ischemia. • rhFGF21 attenuates OGD-induced primary cortical neuronal death. • rhFGF21 protects neurons against OGD injury by inhibiting neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Background Seasonal influenza infections among young children in China lead to substantial numbers of hospitalizations and financial burden. This study assessed the seasonal influenza vaccine effectiveness (VE) against laboratory confirmed medically attended influenza illness among children in Suzhou, China, from October 2011–September 2012. Methods We conducted a test-negative case–control study among children aged 6–59 months who sought care at Soochow University Affiliated Children's Hospital (SCH) from October 2011–September 2012. A case was defined as a child with influenza-like illness (ILI) or severe acute respiratory infection (SARI) with an influenza-positive nasopharyngeal swab by rRT-PCR. Controls were selected from children presenting with ILI or SARI without laboratory confirmed influenza. We conducted 1:1 matching by age and admission date. Vaccination status was verified from the citywide immunization system database. VE was calculated with conditional logistic regression: (1 − OR) × 100%. Result During the study period, 2634 children aged 6–59 months presented to SCH with ILI (1975) or SARI (659) and were tested for influenza. The vaccination records were available for 69% (1829; ILI: 1354, SARI: 475). Among those, 23% (427) tested positive for influenza, and were included as cases. Among influenza positive cases, the vaccination rates were 3.2% for SARI and 4.5% for ILI. Among controls, the vaccination rates were 13% for SARI, and 11% for ILI. The overall VE against lab-confirmed medically attended influenza virus infection was 67% (95% CI: 41–82). The VE for SARI was 75% (95% CI: 11–93) and for ILI was 64% (95% CI: 31–82). Conclusions The seasonal influenza vaccine was effective against medically attended lab-confirmed influenza infection in children aged 6–59 months in Suzhou, China in the 2011–12 influenza season. Increasing seasonal influenza vaccination among young children in Suzhou may decrease medically attended influenza-associated ILI and SARI cases in this population. [ABSTRACT FROM AUTHOR]

Abstract: An environmental, economic and highly effective method for carbon fiber hydroxylated-functionalization based on Fenton''s reagent treatment is used to improve the electrochemical activity of graphite felt (GF) as the positive electrode in all vanadium redox flow battery (VRFB). The effect of H2O2 content in Fenton''s reagent on the structure and electrochemical properties of GF is investigated. The scanning electron microscope (SEM) indicates that the surface of the treated GF is etched increasingly with the content of H2O2. The Fourier transformation infrared (FTIR) spectroscopy shows that the peak intensity of hydroxyl groups on the treated felt is increased with the H2O2 concentration, which is further verified by X-ray photoelectron spectroscopy (XPS). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) show that the treated sample exhibits a higher electrochemical activity. A VRFB with the treated GF as electrodes exhibits higher coulombic, voltage and energy efficiency (98.8%, 75.1% and 74.2%) than that with the untreated GF (93.9%, 72.1% and 67.7%) at 60mAcm−2, and this method is even superior when compared with the reported methods. [Copyright &y& Elsevier]

Herein, a high-efficiency photoactive material, hollow ZnIn 2 S 4 nanocages (ZIS-HNCs) composed of ultrathin nanosheets were creatively synthesized via a metal-organic framework (MOF) derived solvothermal method. It had been specified the underlying mechanism of the ZIS-HNCs evolution under the MOF templated surface. Subsequently, the obtained ZIS-HNCs combined with annealing TiO 2 modified electrode (ZIS-HNCs@TiO 2), and the ZIS-HNCs@TiO 2 exhibited intense transient photocurrent. The enhanced photocurrent signal benefited from the multiple light capture effect of ZIS-HNCs, ultrathin nanosheet subunits of ZIS-HNCs, and typical type Ⅱ heterojunction, which could effectively retard the photoexcited electron-hole pairs recombination, and accelerated charge separation and transfer. Taking antibiotic lincomycin (Lin) as a model, a signal-off photoelectrochemical (PEC) aptasensor based on the ZIS-HNCs@TiO 2 was established and manifested a high sensitive detection for Lin with a linear response range from 0.0001 to 0.1 nM as well as an ultralow detection limit of 0.084 pM. Additionally, the proposed PEC aptasensor showed acceptable stability and remarkable selectivity. Therefore, this study provides a promising strategy to design nanomaterials with superior photoelectric activity for PEC sensing applications. • A hollow ZnIn 2 S 4 nanocage with ultrathin nanosheet subunits was creatively synthesized. • The well-engineered ZIS-HNCs exhibited the promoted visible light harvesting and photoelectric conversion efficiency. • The evolution mechanism of ZIS-HNCs and the enhanced PEC sensing properties were studied in detail. • The PEC aptasensor based on ZIS-HNCs@TiO 2 for lincomycin manifested high sensitivity and ultralow limit of detection. [ABSTRACT FROM AUTHOR]