Investigation of ATP-mediated interleukin-1 secretion in human decidua

Introduction The maternal immune system plays a significant role in pregnancy maintenance. Infections during pregnancy could stimulate inflammatory responses and lead to adverse pregnancy outcomes. Interleukin-1 (IL-1), a vital pro-inflammatory cytokine, is implicated in pregnancy infection and infection-induced preterm labour. Meanwhile, human decidua, situated between the fetus and myometrium, has been hypothesized as the main source of cytokines in the presence of infection. Moreover, the most studied inflammasome–NLRP3 inflammasome, involved in the canonical IL-1β secretory pathway, has been found participating in normal pregnancy and pregnancy disorders. However, knowledge about how decidua is involved in the immune response is still limited. In this study, we investigated how IL-1β release with stimuli to TLR4 and the purinergic P2X7 receptor in the full-term decidua, especially on the key components of the inflammasome pathway. Method Full-term decidua explants, decidual leukocytes, decidual stromal cells and maternal peripheral blood mononuclear cells were isolated. Tissue explants and cells were stimulated with or without the TLR4 agonist-LPS and the P2X7 receptor antagonist-A7 for 4 hours, and the last half hour stimulated with or without P2X7 receptor agonist-BzATP. The secretion of IL-1β and TNF- in culture media were detected by ELISA assay. The pro-IL-1β and NLRP3 inflammasome components proteins including NLRP3, caspase-1 and ASC in tissue lysates and culture media were evaluated by western blotting or ELISA. Results The levels of active IL-1β were higher under single stimulation with LPS in both of decidual tissue explants and maternal, and BzATP could significantly increase IL-1β release, while A7 could inhibit this increased effect. Besides, NLRP3, caspase-1, ASC are expressed in human decidual explants, and the expression of pro-caspase-1 increased after treatment with LPS. Also, NLRP3, p20 caspase-1, and ASC can be detected in culture media consistently, even without treatment. For the decidua cell types, decidual leukocytes, instead of stromal cells, can release IL-1β under costimulation with LPS and BzATP. Moreover, TNF- secretion would be triggered with single stimulation with LPS in decidua explants, maternal PBMC, but these secretions were not affected by BzATP nor A7. Conclusion This study demonstrated that decidua explants can release IL-1β and TNF- in response to LPS stimulation. Besides, exogenous BzATP could enhance the release of IL-1β, but not TNF-, potentially through P2X7 receptor. Furthermore, the expression of NLRP3 inflammasome components in decidua and the increased level of NLRP3 and caspase-1 after stimulation provided a clue that inflammasome may play a vital role in processing IL-1β in human decidua

A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure

BackgroundPostoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients’ clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability.MethodsWe enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome.ResultsWe built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models.ConclusionsThe multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS

Conceptual planning of urban–rural green space from a multidimensional perspective: A case study of Zhengzhou, China

The structure and function of green-space system is an eternal subject of landscape architecture, especially due to limited land and a need for the coordinated development of PLEs (production, living, and ecological spaces). To make planning more scientific, this paper explored green-space structure planning via multidimensional perspectives and methods using a case study of Zhengzhou. The paper applies theories (from landscape architecture and landscape ecology) and technologies (like remote sensing, GIS—geographic information system, graph theory, and aerography) from different disciplines to analyze current green-space structure and relevant physical factors to identify and exemplify different green-space planning strategies. Overall, our analysis reveals that multiple green-space structures should be considered together and that planners and designers should have multidisciplinary knowledge. For specific strategies, the analysis finds (i) that green complexes enhance various public spaces and guide comprehensive development of urban spaces; (ii) that green ecological corridors play a critical role in regional ecological stability through maintaining good connectivity and high node degree (Dg) and betweenness centrality index (BC) green spaces; (iii) that greenway networks can integrate all landscape resources to provide more secured spaces for animals and beautiful public spaces for humans; (iv) that blue-green ecological networks can help rainwater and urban flooding disaster management; and (v) that green ventilation corridors provide air cleaning and urban cooling benefits, which can help ensure healthy and comfortable urban–rural environments. In our view, this integrated framework for planning and design green-space structure helps make the process scientific and relevant for guiding future regional green-space structure

The contribution of female community health volunteers (FCHVs) to maternity care in Nepal: a qualitative study.

BACKGROUND: In resource-poor settings, the provision of basic maternity care within health centres is often a challenge. Despite the difficulties, Nepal reduced its maternal mortality ratio by 80% from 850 to an estimated 170 per 100,000 live births between 1991 and 2011 to achieve Millennium Development Goal Five. One group that has been credited for this is community health workers, known as Female Community Health Volunteers (FCHVs), who form an integral part of the government healthcare system. This qualitative study explores the role of FCHVs in maternal healthcare provision in two regions: the Hill and Terai. METHODS: Between May 2014 and September 2014, 20 FCHVs, 11 health workers and 26 service users were purposefully selected and interviewed using semi-structured topic guides. In addition, four focus group discussions were held with 19 FCHVs. Data were analysed using thematic analysis. RESULTS: All study participants acknowledged the contribution of FCHVs in maternity care. All FCHVs reported that they shared key health messages through regularly held mothers' group meetings and referred women for health checks. The main difference between the two study regions was the support available to FCHVs from the local health centres. With regular training and access to medical supplies, FCHVs in the hill villages reported activities such as assisting with childbirth, distributing medicines and administering pregnancy tests. They also reported use of innovative approaches to educate mothers. Such activities were not reported in Terai. In both regions, a lack of monetary incentives was reported as a major challenge for already overburdened volunteers followed by a lack of education for FCHVs. CONCLUSIONS: Our findings suggest that the role of FCHVs varies according to the context in which they work. FCHVs, supported by government health centres with emphasis on the use of local approaches, have the potential to deliver basic maternity care and promote health-seeking behaviour so that serious delays in receiving healthcare can be minimised. However, FCHVs need to be reimbursed and provided with educational training to ensure that they can work effectively. The study underlines the relevance of community health workers in resource-poor settings

Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats

Pain is the most severe and common symptom of endometriosis. Its underlying pathogenetic mechanism is poorly understood. Nerve sensitization is a particular research challenge, due to the limitations of general endometriosis models and sampling nerve tissue from patients. The chemokine fractalkine (FKN) has been demonstrated to play a key role in various forms of neuropathic pain, while its role in endometriotic pain is unknown. Our study was designed to explore the function of FKN in the development and maintenance of peripheral hyperalgesia and central sensitization in endometriosis using a novel endometriosis animal model developed in our laboratory. After modeling, behavioral tests were carried out and the optimal time for molecular changes was obtained. We extracted ectopic tissues and L4–6 spinal cords to detect peripheral and central roles for FKN, respectively. To assess morphologic characteristics of endometriosis-like lesions—as well as expression and location of FKN/CX3CR1—we performed H&E staining, immunostaining, and western blotting analyses. Furthermore, inhibition of FKN expression in the spinal cord was achieved by intrathecal administration of an FKN-neutralizing antibody to demonstrate its function. Our results showed that implanted autologous uterine tissue around the sciatic nerve induced endometriosis-like lesions and produced mechanical hyperalgesia and allodynia. FKN was highly expressed on macrophages, whereas its receptor CX3CR1 was overexpressed in the myelin sheath of sciatic nerve fibers. Overexpressed FKN was also observed in neurons. CX3CR1/pp38-MAPK was upregulated in activated microglia in the spinal dorsal horn. Intrathecal administration of FKN-neutralizing antibody not only reversed the established mechanical hyperalgesia and allodynia, but also inhibited the expression of CX3CR1/pp38-MAPK in activated microglia, which was essential for the persistence of central sensitization. We concluded that the FKN/CX3CR1 signaling pathway might be one of the mechanisms of peripheral hyperalgesia in endometriosis, which requires further studies. Spinal FKN is important for the development and maintenance of central sensitization in endometriosis, and it may further serve as a novel therapeutic target to relieve persistent pain associated with endometriosis

Brain age predicted using graph convolutional neural network explains neurodevelopmental trajectory in preterm neonates

OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: •Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. •Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. •The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates

Identification and characterization of gonadotropin-releasing hormone (GnRH) in Zhikong scallop Chlamys farreri during gonadal development

Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on neuroendocrine control of gonadal function, such as the function of GnRH during gonadal development is limited. In this study, we investigated the morphology and structure of the nerve ganglia of Zhikong scallop Chlamys farreri by physiological and histological observations. We also cloned the ORF and studied the expression patterns of GnRH in the scallop. Tissue expression analysis showed that GnRH was highly expressed in parietovisceral ganglion (PVG). The in situ hybridization result further confirmed that GnRH mRNA only distributed in some good-sized neurons in the posterior lobe (PL) and some pint-sized neurons in the lateral lobe (LL). In addition, by examining the expression of GnRH during gonadal development in ganglia, we found GnRH displayed higher expression in the female scallops, and showed significant high expression at the growing stage of female scallops in PVG. This study would contribute to gaining insight into the mechanism underlying reproduction regulation by GnRH in the scallop and help to provide a better understanding of reproductive neuroendocrine in mollusks

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called "mutated allele revealed by sequencing with aneuploidy and linkage analyses" (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.Chemistry and Chemical Biolog

Job burnout among primary healthcare workers during COVID-19 pandemic: cross-sectional study in China

ObjectiveThis study evaluated job burnout among primary healthcare workers (PHCWs) in China during the COVID-19 pandemic, explored its influencing factors, and examined PHCWs' preferences for reducing job burnout.MethodWe conducted a multicenter cross-sectional study in Heilongjiang, Sichuan, Anhui, Gansu, and Shandong Provinces. An electronic questionnaire survey was conducted through convenience sampling in communities from May to July 2022. We collected sociodemographic characteristics, job burnout level, job satisfaction, and preferred ways to reduce job burnout among PHCWs.ResultsThe job burnout rate among PHCWs in China was 59.87% (937/1565). Scores for each dimension of job burnout were lower among PHCWs who had a better work environment (emotional exhaustion OR: 0.60; depersonalization OR: 0.73; personal accomplishment OR: 0.76) and higher professional pride (emotional exhaustion OR: 0.63; depersonalization OR: 0.70; personal accomplishment OR: 0.44). PHCWs with higher work intensity (emotional exhaustion OR: 2.37; depersonalization OR: 1.34; personal accomplishment OR: 1.19) had higher scores in all job burnout dimensions. Improving work environments and raising salaries were the preferred ways for PHCWs to reduce job burnout.ConclusionStrategies should be developed to improve job satisfaction among PHCWs, enhance their professional identity, and alleviate burnout to ensure the effective operation of the healthcare system, especially during periods of overwork