Effect of maternal age on foetal chromosomal defects: an investigation based on non-invasive prenatal testing.

BACKGROUND: This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. METHODS: Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses. RESULTS: The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20-24, 25-29, 30-34, 35-39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20-24 years group was 41.67%, that in the 25-29 years group was 62.5%, that in the 30-34 years group was 66.67%, that in the 35-39 years group was 90.74%, and that in the >40 years group was 90.32%. CONCLUSION: Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.

It is critical to diagnose foetal chromosome aneuploidy in time through prenatal screening to prevent birth defects. This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. A retrospective analysis based on NIPT screening data at a medical laboratory was performed. The results showed that the total positivity rate and total positive predictive value of trisomy 21, trisomy 18, and trisomy 13 in older pregnant women (≥35 years old) were significantly higher than those in younger pregnant women, and there was an increasing trend with increasing maternal ages. This study indicated that NIPT detection in elderly pregnant women has an excellent application value in clinical practice to reduce the incidence of birth defects and abortion caused by invasive chromosome examination.

Catchment-scale life cycle impacts of green infrastructures and sensitivity to runoff coefficient with stormwater modelling.

Urban green infrastructure (GI) has been widely used in sponge city construction to manage hydrological processes. While studies on environmental benefits of GI from the perspective of whole life cycle assessment (LCA) have been reported in recent years, few have explored and compared the environmental performance of different GIs within a single catchment, which is directly linked to catchment-scale hydrological control. This study focuses on a Sponge City pilot project in Shenzhen, China, including three typical types of GI: permeable pavement, green roof, and sunken green space. By collecting hydrological data, land use, and life cycle inventory of GI and employing SWMM (Storm Water Management Model)-based stormwater modelling, we have revealed the environmental impacts at different stages of the life cycle of the GI scenario and three GIs through comparative and sensitivity analyses. Notably, we have disclosed, for the first time, the effect of the runoff coefficient in LCA. Our findings indicate that over the 30-year life cycle, the total environmental impact of the GI scenario is 24 % smaller than that of the hypothetical grey scenario. Permeable pavement exhibits the largest environmental impact per unit area, being 1.8 times and 7.6 times greater than that of the green roof and sunken green space, respectively. The operation stage of the three GIs significantly mitigates eutrophication and climate change. Furthermore, sensitivity analysis demonstrates that an increase in surface runoff undermines the environmental benefits of GIs. These results highlight the importance of embedding stormwater modelling into LCA, enabling catchment-scale integrated evaluation and equivalent assessment of different GIs within a single catchment whereby the influence of external factors such as climate change can be described, which aids in understanding the dynamic environmental performance of GIs. The proposed research framework and results are anticipated to provide valuable guidance for future GI construction and carbon-neutral policies.

Binary Double Network-like Structure: An Effective Energy-Dissipation System for Strong Tough Hydrogel Design.

Currently, hydrogels simultaneously featuring high strength, high toughness, superior recoverability, and benign anti-fatigue properties have demonstrated great application potential in broad fields; thus, great efforts have been made by researchers to develop satisfactory hydrogels. Inspired by the double network (DN)-like theory, we previously reported a novel high-strength/high-toughness hydrogel which had two consecutive energy-dissipation systems, namely, the unzipping of coordinate bonds and the dissociation of the crystalline network. However, this structural design greatly damaged its stretchability, toughness recoverability, shape recoverability, and anti-fatigue capability. Thus, we realized that a soft/ductile matrix is indispensable for an advanced strong tough hydrogel. On basis of our previous work, we herein reported a modified energy-dissipation model, namely, a "binary DN-like structure" for strong tough hydrogel design for the first time. This structural model comprises three interpenetrated polymer networks: a covalent/ionic dually crosslinked tightened polymer network (stiff, first order network), a constrictive crystalline polymer network (sub-stiff, second order network), and a ductile/flexible polymer network (soft, third order network). We hypothesized that under low tension, the first order network served as the sacrificing phase through decoordination of ionic crosslinks, while the second order and third order networks together functioned as the elastic matrix phase; under high tension, the second order network worked as the energy dissipation phase (ionic crosslinks have been destroyed at the time), while the third order network played the role of the elastic matrix phase. Owing to the "binary DN-like" structure, the as-prepared hydrogel, in principle, should demonstrate enhanced energy dissipation capability, toughness/shape recoverability, and anti-fatigue/anti-tearing capability. Finally, through a series of characterizations, the unique "binary DN-like" structure was proved to fit well with our initial theoretical assumption. Moreover, compared to other energy-dissipation models, this structural design showed a significant advantage regarding comprehensive properties. Therefore, we think this design philosophy would inspire the development of advanced strong tough hydrogel in the future.

An integrated supervision framework to safeguard the urban river water quality supported by ICT and models.

Models and information and communication technology (ICT) can assist in the effective supervision of urban receiving water bodies and drainage systems. Single model-based decision tools, e.g., water quality models and the pollution source identification (PSI) method, have been widely reported in this field. However, a systematic pathway for environmental decision support system (EDSS) construction by integrating advanced single techniques has rarely been reported, impeding engineering applications. This paper presents an integrated supervision framework (UrbanWQEWIS) involving monitoring-early warning-source identification-emergency disposal to safeguard the urban water quality, where the data, model, equipment and knowledge are smoothly and logically linked. The generic architecture, all-in-one equipment and three key model components are introduced. A pilot EDSS is developed and deployed in the Maozhou River, China, with the assistance of environmental Internet of Things (IoT) technology. These key model components are successfully validated via in situ monitoring data and dye tracing experiments. In particular, fluorescence fingerprint-based qualitative PSI and Bayesian-based quantitative PSI methods are effectively coupled, which can largely reduce system costs and enhance flexibility. The presented supervision framework delivers a state-of-the-art management tool in the digital water era. The proposed technical pathway of EDSS development provides a valuable reference for other regions.

Integrating the tumor-suppressive activity of Maspin with p53 in retuning the epithelial homeostasis: A working hypothesis and applicable prospects.

Epithelial malignant transformation and tumorous development were believed to be closely associated with the loss of its microenvironment integrity and homeostasis. The tumor-suppressive molecules Maspin and p53 were demonstrated to play a crucial role in body epithelial and immune homeostasis. Downregulation of Maspin and mutation of p53 were frequently associated with malignant transformation and poor prognosis in various human cancers. In this review, we focused on summarizing the progress of the molecular network of Maspin in studying epithelial tumorous development and its response to clinic treatment and try to clarify the underlying antitumor mechanism. Notably, Maspin expression was reported to be transcriptionally activated by p53, and the transcriptional activity of p53 was demonstrated to be enhanced by its acetylation through inhibition of HDAC1. As an endogenous inhibitor of HDAC1, Maspin possibly potentiates the transcriptional activity of p53 by acetylating the p53 protein. Hereby, it could form a "self-propelling" antitumor mechanism. Thus, we summarized that, upon stimulation of cellular stress and by integrating with p53, the aroused Maspin played the epigenetic surveillant role to prevent the epithelial digressional process and retune the epithelial homeostasis, which is involved in activating host immune surveillance, regulating the inflammatory factors, and fine-tuning its associated cell signaling pathways. Consequentially, in a normal physiological condition, activation of the above "self-propelling" antitumor mechanism of Maspin and p53 could reduce cellular stress (e.g., chronic infection/inflammation, oxidative stress, transformation) effectively and achieve cancer prevention. Meanwhile, designing a strategy of mimicking Maspin's epigenetic regulation activity with integrating p53 tumor-suppressive activity could enhance the chemotherapy efficacy theoretically in a pathological condition of cancer.

Road runoff as a significant nonpoint source of parabens and their metabolites in urban rivers.

Parabens are widely added to food, cosmetics, and medicines as preservatives and are typical contaminants of pharmaceuticals and personal care products (PPCPs). However, their fate and transport in urban watersheds remain largely unexplored. This study investigated the role of road runoff as a critical nonpoint source of parabens and their metabolites in urban rivers based on 73 multimedia (road runoff and dust in different urban land uses, wastewater, stormwater discharge and river water) samples collected from a highly urbanized drainage area. Seven parabens and five metabolites were detected in the road runoff, with mean concentrations of ∑parabens and ∑metabolites equal to 47.5 ng/L and 4710 ng/L, respectively. The concentrations in road runoff were comparable to those in treated wastewater and river water and showed a land use pattern of residential > industrial > commercial. A first flush effect of the contaminants was observed in a heavy rainfall event with an antecedent dry period. In general, the population-based and area-based emission intensities of ∑parabens and ∑metabolites in road runoff were one order of magnitude higher than those in wastewater effluent during the rainfall events. This study provides quantitative evidence that road runoff can be a major pollution source of parabens and their metabolites in rapidly growing cities during the wet season and calls for the integrated management of nonpoint sources to prevent urban river contamination by typical PPCPs.

Perceived Organizational Support and Proactive Innovation Behavior: The Mediating Role of Basic Psychological Needs.

Drawing upon self-determination theory, this study aimed to explore the mechanisms underlying the impact of perceived organizational support on proactive innovation behavior and reveal the serial mediation effects of basic psychological needs. We collected time-lagged data of 481 employees from research institutions in China, and structural equation modeling analyses were carried out to test the hypotheses. The results indicate that perceived organizational support is significantly and positively related to proactive innovation behavior, and this relationship was mediated by the need for autonomy, competence, and relatedness. These findings contribute new knowledge to proactive innovation behavior by providing a new perspective of the satisfaction of psychological needs. Theoretical and practical implications are discussed.

Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells.

PURPOSE: To study bacterial lipopolysaccharide (LPS)-induced cancer stem-like transformation and to investigate the inhibitory effect of Trichostatin A (TSA) on the malignant transformation through targeting p-Stat3 signaling. METHODS: 2D, 3D, and serum-free suspension culture system were used to study LPS-induced malignant transformation in series malignant grade of prostate cancer (PCa) epithelial cells. Flow cytometry assay and RT-PCR were utilized to evaluate the CD44+CD133+ stem cell population, the expression of inflammatory cytokines and series tumor stemness biomarkers. Meanwhile, Western blot was used to analyze the alteration of cell signaling associated-molecules by treatment with TSA, an original antifungal antibiotic and a panel inhibitor of histone deacetylase. RESULTS: Our study found that LPS promoted the migration, invasion and stem-like tumoroshpere forming in multiple PCa cell lines including DU145, PC3, 22RV1, LNCaP. LPS also enriched CD44+CD133+ stem cell population and increased the expression of series tumor stemness biomarkers (e.g., CD44, CD133, SOX-2, α-intergrin, Nestin, etc.). TSA was found to prevent tumor cell migration, invasion and tumorosphere forming in DU145 and PC3 cells with increasing tumor suppressive Maspin and reducing both phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in LPS-treated DU145 cells. Furthermore, blocking Stat3 signaling pathway by treatment with TSA and/or small molecule compound Stattic of an p-Stat3 inhibitor effectively abrogated LPS-induced tumorosphere forming with decrease of IL-6, IL-8 and stemness biomarkers CD44, SOX-2 expression. CONCLUSION: Our data demonstrated that the inflammatory agent of bacterial LPS augmented malignant transformation and promoted the cancerous stemness in PCa epithelial cells. TSA could prevent, at least in part, the LPS-induced malignant transformation by targeting p-Stat3/c-Myc signaling pathway and reducing inflammatory IL-6, IL-8. In addition, the assay of LPS-induced tumorosphere forming could serve as a simple and an easy handling method for targeting cancer stem cells drug screening in vitro in clinical practice.

The Differential Antitumor Activity of 5-Aza-2'-deoxycytidine in Prostate Cancer DU145, 22RV1, and LNCaP Cells.

DNA methylation is a DNA methyltransferase-mediated epigenetic modification affecting gene expression. This process is involved in the initiation and development of malignant disease. 5-Aza-2'-deoxycytidine (5-Aza), a classic DNA methyltransferase inhibitor, possesses antitumor proliferation activity. However, whether 5-Aza induces cytotoxicity in solid tumors warrants further investigated. In this study, human prostate cancer (CaP) cells were treated with 5-Aza and subjected to cell viability and cytotoxicity analysis. Reverse transcription-polymerase chain reaction and methylation-specific polymerase chain reaction assay were utilized to test the gene expression and methylation status of the p53 and p21 gene promoters. The results showed that 5-Aza differentially inhibited spontaneous proliferation, arrested the cell cycle at S phase in DU145, at G1 phase in 22RV1 and LNCaP cells, and G2 phase in normal RWPE-1 cells, as well as induced the expression of phospho-H2A.X and tumor suppressive mammary serine protease inhibitor (maspin) in all three types of CaP cells. 5-Aza also increased p53 and p21 transcription through promoter demethylation, and decreased the expression of oncogene c-Myc in 22RV1 and LNCaP cells. Western blotting analysis showed that the poly (ADP-ribose) polymerase cleavage was detected in DU145 and 22RV1 cells. Moreover, there were no significant changes in p53, p21 and c-Myc expression in DU145 cells following treatment with 5-Aza. Thus, in responsible for its apoptotic induction and DNA damage, the mechanism of the antitumor activities of 5-Aza may involve in an increase of tumor suppressive maspin, upregulation of wild type p53-mediated p21 expression and a decrease of oncogene c-Myc level in 22RV1 and LNCaP cells, and enhancing the tumor suppressive maspin expression in DU145 cells. These results enriched our understanding of the multifaceted antitumor activity of 5-Aza, and provided the expression basis of biomarkers for its possible clinical application in prostate cancer.

Robustness analysis of storm water quality modelling with LID infrastructures from natural event-based field monitoring.

Sponge city construction (SCC) in China, as a new concept and a practical application of low-impact development (LID), is gaining wide popularity. Modelling tools are widely used to evaluate the ecological benefits of SCC in stormwater pollution mitigation. However, the understanding of the robustness of water quality modelling with different LID design options is still limited due to the paucity of water quality data as well as the high cost of water quality data collection and model calibration. This study develops a new concept of 'robustness' measured by model calibration performances. It combines an automatic calibration technique with intensive field monitoring data to perform the robustness analysis of storm water quality modelling using the SWMM (Storm Water Management Model). One of the national pilot areas of SCC, Fenghuang Cheng, in Shenzhen, China, is selected as the study area. Five water quality variables (COD, NH3-N, TN, TP, and SS) and 13 types of LID/non-LID infrastructures are simulated using 37 rainfall events. The results show that the model performance is satisfactory for different water quality variables and LID types. Water quality modelling of greenbelts and rain gardens has the best performance, while the models of barrels and green roofs are not as robust as those of the other LID types. In urban runoff, three water quality parameters, namely, SS, TN and COD, are better captured by the SWMM models than NH3-N and TP. The modelling performance tends to be better under heavy rain and significant pollutant concentrations, denoting a potentially more stable and reliable design of infrastructures. This study helps to improve the current understanding of the feasibility and robustness of using the SWMM model in sponge city design.

Tumor Suppressive Maspin-Sensitized Prostate Cancer to Drug Treatment Through Negative Regulating Androgen Receptor Expression.

Overactivation of androgen receptor (AR)-mediated signal has been extensively implicated in prostate cancer (CaP) development, progression, and recurrence, which makes it an attractive therapeutic target. Meanwhile, as an endogenous inhibitor of histone deacetylase 1 (HDAC 1), tumor-suppressive mammary serine protease inhibitor (maspin) was reported to sensitize drug-induced apoptosis with a better therapeutic outcome in CaP, but the relationship between AR and maspin remains unclear. In the current study, treatment of 5'-Aza or MS-275/enzalutamide induced poly (ADP-ribose) polymerase (PARP) cleavage and p-H2A.X in CaP cells with an increase of maspin expression but a decrease of AR. Then, treatment with protease inhibitor MG132 did not rescue the above drug-induced loss of AR. In addition, modulation of maspin expression by gene recombinant or siRNA technology showed an inverse correlation between expression of maspin and AR, consequently affecting the AR-regulated downstream gene transcription (e.g., NKX3.1 and TMPRSS2). Bioinformatics analysis of the data extracted from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database also revealed an inverse correlation between low maspin expression and high AR level in advanced CaP. Furthermore, chromatin immunoprecipitation (ChIP) assay using anti-maspin antibody identified that a portion of AR promoter sequence was co-precipitated and presented in the immunoprecipitated complex. Finally, maspin-mediated repression of AR was induced by treatment of MS-275, which promoted enzalutamide treatment efficacy with decrease of prostate-specific antigen (PSA) expression in LNCaP and 22RV1 cells. Taken together, the data not only demonstrated maspin-mediated repression of AR to augment drug anti-tumor activity but also provided in-depth support for combination of HDAC inhibitors with AR antagonist in CaP therapy.

WNT7A Promotes EGF-Induced Migration of Oral Squamous Cell Carcinoma Cells by Activating ß-Catenin/MMP9-Mediated Signaling.

AIMS AND HYPOTHESIS: Epidermal growth factor (EGF) has been shown to induce the migration of various cancer cells. However, the underlying signaling mechanisms for EGF-induced migration of oral squamous cell carcinoma (OSCC) remain to be elucidated. WNT7A, a member of the family of 19 Wnt secreted glycoproteins, is commonly associated with tumor development. It is mostly unknown whether and, if so, how EGF modulates WNT7A in OSCC cells. The role of WNT7A in OSCC was thus investigated to explore the underlying signaling mechanisms for EGF-induced migration of OSCC. METHODS: Cell migration was measured by Wound healing assay and Transwell assay. Western blotting was carried out to detect the expression of WNT7A, MMP9, ß-catenin, p-AKT, and p-ERK. The cells were transfected with plasmids or siRNA to upregulate or downregulate the expression of WNT7A. The location of ß-catenin was displayed by immunofluorescence microscopy. Immunohistochemistry was carried out to confirm the relation between WNT7A expression and OSCC progression. RESULTS: The present study showed that the levels of WNT7A mRNA and protein were increased by EGF stimulation in OSCC cells. Besides, it was proved that p-AKT, but not p-ERK, mediated the expression of WNT7A protein induced by EGF. Furthermore, the inhibition of AKT activation prevented the EGF-induced increase of WNT7A and matrix metallopeptidase 9 (MMP9) expression and translocation of ß-catenin from the cytoplasm to the nucleus. Moreover, histological analysis of OSCC specimens revealed an association between WNT7A expression and poor clinical prognosis of the disease. CONCLUSIONS: The data in this paper indicated that WNT7A could be a potential oncogene in OSCC and identified a novel PI3K/AKT/WNT7A/ß-catenin/MMP9 signaling for EGF-induced migration of OSCC cells.

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway.

Tumor cell migration is a critical step in cancer metastasis. Over-activated Notch pathway can promote the migration of cancer cells, especially in the breast cancer. However, the underlying mechanism of non-canonical Notch signaling in modulating the migration has not yet been clearly characterized. Here we demonstrated that DAPT, a gamma secretase inhibitor, inhibited protrusion formation and cell motility, and then reduced the migration of triple-negative breast cancer cells, through increasing the activity of Cdc42 by non-canonical Notch pathway. Phosphorylation of AKT on S473 was surprisingly increased when Notch signaling was inhibited by DAPT. Inhibition of PI3K and AKT by LY294002 and MK2206, respectively, or knockdown of AKT expression by siRNA blocked DAPT-induced activation of Cdc42. Moreover, immunofluorescence staining further showed that DAPT treatment reduced the formation of lamellipodia and induced actin cytoskeleton remodeling. Taken together, these results indicated that DAPT inhibited Notch signaling and consequently activated PI3K/AKT/Cdc42 signaling by non-canonical pathway, facilitated the formation of filopodia and inhibited the assembly of lamellipodia, and finally resulted in the decrease of migration activity of breast cancer cells.

Negative-Pressure Wound Therapy Promotes Wound Healing by Enhancing Angiogenesis Through Suppression of NLRX1 via miR-195 Upregulation.

Negative-pressure wound therapy (NPWT) is one of the most advanced therapeutic methods in the treatment of various hard-to-heal acute and refractory chronic wounds. Recent emerging evidence points to a role of the microRNA-mediated regulation of angiogenesis in ischemic tissues, and a series of microRNAs associated with angiogenesis have been successively identified. In this study, we found that miR-195 expression was significantly upregulated and the microvessel density (MVD) was increased in granulation tissue collected 7 days after NPWT compared with those in the pre-NPWT tissue. Moreover, the expression of NLRX1, the potential target gene of miR-195, was down-regulated in post-NPWT compared with that in pre-NPWT tissue. Significant negative correlations were detected between miR-195 and NLRX1 expression levels ( r = -.856, P < .001) and between NLRX1 expression and MVD ( r = -.618, P < .05), whereas miR-195 expression was positively correlated with MVD in the granulation tissue ( r = .630, P < .05). In summary, NPWT may suppress NLRX1 expression through the upregulation of miR-195 expression, thus efficaciously promoting angiogenesis in the granulation tissue to enhance wound healing.

Abnormal amphiregulin expression correlates with gastric cancer prognosis.

Gastric cancer (GC) is a global health issue with a high mortality rate. Early diagnosis and tracking of GC is a challenge due to a lack of reliable tools. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family that activates growth signaling upon binding of EGF receptors. Elevated AREG expression is associated with various pathological conditions, including cancer. Here, we investigated whether increased AREG expression is a disease indicator and/or prognostic biomarker for GC. We used tissue microarray and quantitative real-time polymerase chain reaction to assess AREG expression in clinical tissue specimens at various stages of GC and a conducted bioinformatics analysis to evaluate the value of AREG over-expression as a GC biomarker. We found that both mRNA and protein expression of AREG were increased in the tissues of GC patients when compared to tissues from non-cancer patients or normal tissues. High expression of AREG was also associated with GC clinicopathological characteristics and poor survival. Thus, over-expression of AREG could serve as a novel GC biomarker, and active surveillance of its expression could be a novel approach to GC diagnosis and monitoring.