Relationship between affiliate stigma and family quality of life among parents of children with autism spectrum disorders: The mediating role of parenting self-efficacy.

BACKGROUND: The parents of children with autism spectrum disorder (ASD) are under great pressure and experience discrimination in their daily lives, which affects their family quality of life (FQOL). OBJECTIVE: METHODS: A total of 237 parents of children with ASD were recruited in a university-affiliated hospital in Guangzhou, China, from October 2020 to April 2021 by convenience sampling. The Affiliate Stigma Scale, Parenting Sense of Competence Scale and Beach Center Family Quality of Life Scale were employed for data collection. RESULTS: The results showed that affiliate stigma negatively predicts total FQOL and the dimensions of FQOL through both a direct effect and an indirect effect through parenting self-efficacy. CONCLUSIONS: The findings suggest that affiliate stigma is an important predictor of FQOL, and interventions to reduce affiliate stigma and strengthen parenting self-efficacy might be effective in improving FQOL in the parents of children with ASD.

Stable and Oscillatory Hypoxia Differentially Regulate Invasibility of Breast Cancer Associated Fibroblasts.

As local regions in the tumor outstrip their oxygen supply, hypoxia can develop, affecting not only the cancer cells, but also other cells in the microenvironment, including cancer associated fibroblasts (CAFs). Hypoxia is also not necessarily stable over time, and can fluctuate or oscillate. Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia, and can also exhibit oscillations in its activity. To understand how stable, and fluctuating hypoxia influence breast CAFs, we measured changes in gene expression in CAFs in normoxia, hypoxia, and oscillatory hypoxia, as well as measured change in their capacity to resist, or assist breast cancer invasion. We show that hypoxia has a profound effect on breast CAFs causing activation of key pathways associated with fibroblast activation, but reduce myofibroblast activation and traction force generation. We also found that oscillatory hypoxia, while expectedly resulted in a "sub-hypoxic" response in gene expression, it resulted in specific activation of pathways associated with actin polymerization and actomyosin maturation. Using traction force microscopy, and a nanopatterned stromal invasion assay, we show that oscillatory hypoxia increases contractile force generation vs stable hypoxia, and increases heterogeneity in force generation response, while also additively enhancing invasibility of CAFs to MDA-MB-231 invasion. Our data show that stable and unstable hypoxia can regulate many mechnobiological characteristics of CAFs, and can contribute to transformation of CAFs to assist cancer dissemination and onset of metastasis.

Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells.

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content in the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited to breast cancer by many mechanisms, including hypoxia, and contribute to metastatic transition of the cancer. Breast cancers are characterized by regions of hypoxia, which can be temporally unstable owing to a mismatch between oxygen supply and consumption. Using a high-sensitivity nanopatterned stromal invasion assay, we found that ASCs could promote stromal invasion of not only breast cancer cell lines but also MCF10A1, a cell line derived from untransformed breast epithelium. RNA sequencing of MCF10A1 cells conditioned with medium from ASCs revealed upregulation of genes associated with increased cell migration, chemotaxis, and metastasis. Furthermore, we found that fluctuating or oscillating hypoxia could induce senescence in ASCs, which could result in an increased invasive potential in the treated MCF10A1 cells. These findings highlight the complex interplay within the breast cancer microenvironment, hypoxia, and the role of ASCs in transforming even non-cancerous breast epithelium toward an invasive phenotype, providing insights into early metastatic events.

Tissue-of-origin for cancers determines HIF-1 activation induced phenotypic heterogeneity.

Hypoxia-inducible factor-1 (HIF-1) is the master regulator of cellular response to hypoxia, and is activated in many cancers contributing to many steps in the metastatic cascade by acting as a key transcription co-regulator for a large number of downstream genes. Presence of hypoxia within a tumor is spatially nonuniform, and can also by dynamic. Further, although HIF-1 is primarily stabilized and activated by lack of molecular O2, its stability is also affected by other factors present in the tumor microenvironment. HIF-1 also crosstalks with other transcription factors in co-regulating gene expression. Consequently, it is nontrivial to predict the gene expression patterns in cells in response to hypoxia, or HIF-1 activation. Additionally, cancers originating from tissue origins with different basal level of partial oxygen tension may activate HIF-1 at different threshold of hypoxia. We analyzed large published single cell RNAseq data for colorectal, lung, and pancreatic cancers to investigate the phenotypic outcome of HIF-1 activation in cancer cells. We found that cancers from tissues with different partial O2 tension levels exhibit HIF-1 activation at different stages of metastasis, and phenotypically respond differently to HIF-1 activation, likely by contextual co-option of different transcription factors. We experimentally confirmed these predictions by using cell lines representative of colorectal, lung, and pancreatic cancers, finding that while hypoxia enhances growth of colorectal cancer, it induces increased invasion of lung, and pancreatic cancers. Our analysis suggest that HIF-1 activation may act as a rheostat regulating downstream gene expression towards phenotypic outcomes differently in various cancers.

PC71BM as Morphology Regulator for Highly Efficient Ternary Organic Solar Cells with Bulk Heterojunction or Layer-by-Layer Configuration.

The ternary strategy is one of the effective methods to regulate the morphology of the active layer in organic solar cells (OSCs). In this work, the ternary OSCs with bulk heterojunction (BHJ) or layer-by-layer (LbL) active layers are prepared by using the polymer donor PM6 and the non-fullerene acceptor L8-BO as the main system and the fullerene acceptor PC71BM as the third component. The power conversion efficiencies (PCEs) of BHJ OSCs and LbL OSCs are increased from 17.10% to 18.02% and from 17.20% to 18.20% by introducing PC71BM into the binary active layer, respectively. The in situ UV-vis absorption spectra indicate that the molecular aggregation and crystallization process can be prolonged by introducing PC71BM into the PM6:L8-BO or PM6/L8-BO active layer. The molecular orientation and molecular crystallinity in the active layer are optimized by introducing the PC71BM into the binary BHJ or LbL active layers, which can be confirmed by the experimental results of grazing incidence wide-angle X-ray scattering. This study demonstrates that the third component PC71BM can be used as a morphology regulator to regulate the morphology of BHJ or LbL active layers, thus effectively improving the performance of BHJ and LbL OSCs.

The importance of parenting self-efficacy and social support for family quality of life in children newly diagnosed with autism spectrum disorder: A one-year follow-up study.

Improving the quality of family life (FQoL) is one of the ultimate goals for autism spectrum disorder (ASD) intervention, and parenting self-efficacy and social support are critical for the well-being of families. However, longitudinal studies focusing on FQoL and its predictors for families of children with ASD are scarce. This study aims to describe the characteristics of FQoL among parents of children newly diagnosed with ASD at two waves (newly diagnosed and diagnosed after one year) and to explore the predictors of FQoL at two waves. It was conducted at a tertiary hospital in Guangzhou, China. A total of 156 parents and their children were included in Wave 1, followed up with 110 in Wave 2 after 1 year. The overall satisfaction of FQoL improved (t = -2.128, p < 0.05), while satisfaction with physical/material well-being decreased (t = 5.972, p < 0.01). Additionally, the overall importance rating of FQoL improved but did not have statistical significance (p > 0.05). Parents with higher parenting self-efficacy (ß = 0.716, P < 0.01), and more subjective social support (ß = 1.127, p < 0.001) reported higher satisfaction with FQoL, and those with better social support utilization (ß = 1.066, p < 0.05) reported higher importance for FQoL. FQoL needs to be improved in the early stage of ASD diagnosis, and parental self-efficacy and social support can serve as the intervention targets.

Predictors of posttraumatic growth in 475 Chinese parents of children newly diagnosed with autism spectrum disorder.

PURPOSE: To examine the predictive effects of children's symptom severity, rumination, parental self-efficacy, and social support on posttraumatic growth (PTG) in parents of autistic children. DESIGN AND METHODS: Parents (n = 475) completed the demographic questionnaire, Posttraumatic Growth Inventory, Autism Behavior Checklist, Event Related Rumination Inventory, Parenting Sense of Competence, and Social Support Rating Scale in a cross-sectional survey conducted in a tertiary hospital in Guangzhou, China, between September 2019 and January 2021. Multiple linear regression analyses were conducted using SPSS version 25.0. RESULTS: The PTG score was positively associated with rumination (r = 0.325, P < 0.05), parental self-efficacy (r = 0.219, P < 0.05), and social support (r = 0.374, P < 0.05). Multiple linear regression analysis revealed that household income (ß = 0.095, P < 0.05), intrusive rumination (ß = -0.100, P < 0.05), deliberate rumination (ß = 0.391, P < 0.001), subjective support (ß = 0.239, P < 0.001), and children's daily living skills deficiencies as perceived by parents (ß = 0.107, P < 0.05) significantly predicted PTG, accounting for 33.3% of the variance [F(P) = 13.444, P < 0.001]. CONCLUSIONS: Psychosocial factors (rumination and subjective support) are essential to facilitate PTG in parents whose children are newly diagnosed with autism. PRACTICE AND IMPLICATIONS: With the consideration of different sociodemographic features, clinicians and researchers are encouraged to explore cognitive-based psychosocial interventions targeting parents' psychological growth and parenting training programs targeting autistic children's self-care ability.

Improving early detection, diagnosis and intervention for children with autism spectrum disorder: A cross-sectional survey in China.

BACKGROUND: Detection and diagnosis of autism spectrum disorder (ASD) are prerequisites for early interventions. However, few studies focused on this topic. AIM: This study aims to characterize the timing from symptom detection to intervention in children with ASD and identify predictors of age at ASD diagnosis, presence of intervention, and the time lag between detection and diagnosis. METHODS AND PROCEDURES: A cross-sectional survey was conducted with 303 parents (111 fathers and 192 mothers, 21-54 years) of children with ASD in Guangzhou, China. OUTCOMES AND RESULTS: The median time from symptom observation to the first doctor visit was 3 months, while the time to ASD diagnosis averaged 6 months. Most children (76.24 %) were diagnosed within one year after detection, and 25.58 % had no intervention after diagnosis. Predictors of earlier ASD diagnosis included ASD-related symptoms identified at an older age, less serious symptoms, and initial symptoms with atypical motor development and sensory anomalies. ASD-related symptoms observed at an older age, initial symptoms with social deficits, sensory anomalies, and without language impairment, primary caregivers other than parents, families with lower income, and less social support utilization increased the odds of a time lag between detection and diagnosis. Children with fathers having lower education were less likely to receive interventions. CONCLUSIONS AND IMPLICATIONS: Earlier ASD identification and intervention might be facilitated by health education on typical symptoms of ASD for parents with young children and incorporating ASD screening during routine health examinations for children. For children whose primary caregivers are not their parents and from lower-income families, additional support may be required for timely diagnosis after reporting ASD-related symptoms. Moreover, more intervention supports are expected for children whose fathers have lower education levels. Helping families take full advantage of support is also important for early diagnosis and intervention.

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Idiopathic pulmonary hypertension (IPAH) is a rare and devastating disease often accompanied by persistent inflammation and immune responses. We aim to provide a reference atlas of neutrophils to facilitate a better understanding of cellular phenotypes and discovery of candidate genes. METHODS: Peripheral neutrophils from naive patients with IPAH and matched controls were profiled. Whole-exon sequencing was performed to exclude known genetic mutations before establishing single-cell RNA sequencing. Marker genes were validated by flow cytometry and histology in a separate validation cohort. RESULTS: Seurat clustering analysis revealed that the landscape of neutrophils encompassed 5 clusters, including 1 progenitor, 1 transition, and 3 functional clusters. The intercorrelated genes in patients with IPAH were mainly enriched in antigen processing presentation and natural killer cell mediated cytotoxicity. We identified and validated differentially upregulated genes, including MMP9 (matrix metallopeptidase 9), ISG15 (ISG15 ubiquitin-like modifier), and CXCL8 (C-X-C motif ligand 8). The positive proportions and fluorescence quantification of these genes were significantly increased in CD16+ neutrophils in patients with IPAH. The higher proportion of positive MMP9 neutrophils increased mortality risk after adjustment for age and sex. Patients with higher proportions of positive MMP9 neutrophils had worse survival, while the fraction of ISG15- or CXCL8-positive expression neutrophils failed to predict outcome. CONCLUSIONS: Our study yields a comprehensive dataset of the landscape of neutrophils in patients with IPAH. The predictive values of a neutrophil cluster characterized by higher MMP9 expression indicate a functional role for neutrophil-specific matrix metalloproteinases in the pathogenesis of pulmonary arterial hypertension.

Spatiotemporal trends of cardiovascular disease burden attributable to ambient PM2.5 from 1990 to 2019: A global burden of disease study.

There is little known about the global burden of CVD attributable to ambient PM2.5 (referred to as CVD burden hereinafter) and its secular trend across different regions and countries. We aimed to evaluate the spatiotemporal trends in CVD burden at the global, regional and national levels from 1990 to 2019. Data on CVD burden including mortality and disability adjusted of life years (DALYs) from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019. Cases, the age-standardized rate of mortality (ASMR) and DALYs (ASDR) were estimated by age, sex and sociodemographic index (SDI). Estimated annual percentage change (EAPC) was calculated to evaluate the temporal changing in ASDR and ASMR from 1990 to 2019. In 2019, 2.48 million deaths and 60.91 million DALYs of CVD were attributed to ambient PM2.5 globally. Most CVD burden occurred in males, elderly and the middle SDI region. At national level, Uzbekistan, Egypt, and Iraq had the highest ASMR and ASDR. Despite remarkable increase in number of DALYs and deaths of CVD worldwide from 1990 to 2019, we observed nonsignificant change in ASMR (EAPC: 0.06, 95 % CI: -0.01, 0.13) and slight increment in ASDR (EAPC: 0.30, 95 % CI: 0.23, 0.37). The EAPCs of ASMR and ASDR were negatively associated with SDI in 2019, while the low-middle SDI region exhibited the fastest growth of ASMR and ASDR with EAPCs of 3.25 (95 % CI: 3.14, 3.37) and 3.36 (95 % CI: 3.22, 3.49), respectively. In conclusion, the global CVD burden attributable to ambient PM2.5 has largely increased over the past three decades. The population growth, aging and SDI contributed to the heterogeneity of spatial and temporal distribution. Enforcing policy to improving air quality is required to halt the growing burden of PM2.5 on health.

Parenting confidence and social support as predictors of coping strategies in parents of children newly diagnosed with autism spectrum disorder: A cross-sectional study.

AIMS: The aims of the study were to describe coping strategies in parents of children with autism spectrum disorder at the early stage of diagnosis and to examine the predictive effects of parenting confidence and social support on coping strategies. DESIGN: A descriptive cross-sectional study. METHODS: A convenience sample of 193 parents of children newly diagnosed with autism spectrum disorder in Guangzhou, China, were included from October 2020 to January 2021. The Simplified Coping Style Questionnaire, Parenting Sense of Competence Scale and Social Support Rating Scale were employed for data collection. Multiple hierarchical regression analyses examined the relationship between coping strategies and the independent variables. RESULTS: The mean positive coping strategies score was higher than the negative coping strategies score. Parenting efficacy, subjective support and support utilization predicted positive coping strategies, and parenting satisfaction was a protective factor against negative coping strategies. CONCLUSION: Parents tend to engage in positive coping at the early stage of diagnosis. Improving parenting confidence and social support might help parents adopt positive coping strategies and prevent negative coping. IMPACT: More effective and long-term support for families of children with autism spectrum disorder is expected. Interventions should be focused on enhancing parenting satisfaction and efficacy to employ positive coping strategies and decrease negative coping. REPORTING METHOD: We adhered to EQUATOR guidelines and reported results based on STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Creating two-dimensional solid helium via diamond lattice confinement.

The universe abounds with solid helium in polymorphic forms. Therefore, exploring the allotropes of helium remains vital to our understanding of nature. However, it is challenging to produce, observe and utilize solid helium on the earth because high-pressure techniques are required to solidify helium. Here we report the discovery of room-temperature two-dimensional solid helium through the diamond lattice confinement effect. Controllable ion implantation enables the self-assembly of monolayer helium atoms between {100} diamond lattice planes. Using state-of-the-art integrated differential phase contrast microscopy, we decipher the buckled tetragonal arrangement of solid helium monolayers with an anisotropic nature compressed by the robust diamond lattice. These distinctive helium monolayers, in turn, produce substantial compressive strains to the surrounded diamond lattice, resulting in a large-scale bandgap narrowing up to ~2.2 electron volts. This approach opens up new avenues for steerable manipulation of solid helium for achieving intrinsic strain doping with profound applications.

The protective role of social support on prenatal depression among pregnant women of advanced maternal age: a Three-Trimester follow-up study in China.

The aim of this study was to compare the depressive symptoms during pregnancy between pregnant women aged over 35 years and those aged less than 35 years and to evaluate the protective effect of social support in early pregnancy against prenatal depressive symptoms. One hundred and seventy one women aged over 35 years and 342 trimester-matched women aged less than 35 years were included from a level III hospital in Shenzhen, China. The self-report Edinburgh Postnatal Depression Scale (EPDS) and Social Support Rating Scale (SSRS) were used to evaluate prenatal depression and social support in early pregnancy. The proportions of women aged over 35 years who screened positive for prenatal depression were 22.8%, 23.4%, and 24.0% in the first, second and third trimesters, respectively. Advanced maternal age (≥35 years) was a positive predictor of prenatal depressive symptoms (ß = 0.747, P = 0,008). Social support, especially objective support (ß = -0.030, P = 0.002) and subjective support (ß = -0.028, P = 0.006) in early pregnancy, had stronger protective effects against prenatal depressive symptoms for women aged over 35 years than younger women. Our findings support that older pregnant women experience more depressive symptoms than younger pregnant women, and social support could serve as a targeted intervention to decrease prenatal depressive symptoms.Impact statementWhat is already known on this subject? Depressive symptoms, which are strongly associated with adverse psychosocial and birth outcomes, appear to be prevalent and change in nature. Social support is an important protective factor against prenatal depression.What the results of this study add? Pregnant women of advanced maternal age experienced more depressive symptoms than younger women during the prenatal period. Social support, especially objective support and subjective support, had stronger protective effects against prenatal depression for women aged over 35 years than women aged less than 35 years.What the implications of these findings are for clinical practice? Screening of prenatal depression should be strengthened, especially for women aged over 35 years, and improving subjective support could improve their emotional experience.

Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.

Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature-specifically in pulmonary vascular lesions-as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs). Previous studies suggest that altered hemodynamic forces cause lung endothelial dysfunction and, in turn, adherence of immune cells and release of inflammatory mediators, while the resulting perivascular inflammation, in turn, promotes vascular remodeling and the progression of PH. As such, a vicious cycle of endothelial activation, inflammation, and vascular remodeling may develop and drive the disease process. PA stiffening constitutes an emerging research area in PH, with relevance in PH diagnostics, prognostics, and as a therapeutic target. With respect to its prognostic value, PA stiffness rivals the well-established measurement of pulmonary vascular resistance as a predictor of disease outcome. Vascular remodeling of the arterial extracellular matrix (ECM) as well as vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis contribute to PA stiffening. While associations between inflammation and vascular stiffening are well-established in systemic vascular diseases such as atherosclerosis or the vascular manifestations of systemic sclerosis, a similar connection between inflammatory processes and PA stiffening has so far not been addressed in the context of PH. In this review, we discuss potential links between inflammation and PA stiffening with a specific focus on vascular calcification and ECM remodeling in PH.

m6A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling induced by human pulmonary arterial smooth muscle cell (HPASMC) proliferation, migration, and apoptosis resistance. m6A (N6-methyladenosine) is the most prevalent RNA posttranscriptional modification in eukaryotic cells. However, its role in PAH remains elusive. We designed this study to investigate whether m6A modification and its effector proteins play a role in pulmonary vascular resistance. Lung samples were used to profile m6A concentrations in control subjects and patients with PAH. Bioinformatics analysis, real-time PCR, immunohistochemistry, and Western blotting were used to determine the role of m6A effectors in PAH. The biological effects of GRAP modified by m6A were investigated using in vitro and in vivo models. Furthermore, RIP-PCR was used to assess the writers and readers of GRAP. In this study, we revealed that m6A-modified GRAP mRNA was upregulated in PAH lung samples, cHx/Su-induced mouse models, and hypoxia-stimulated HPASMCs; however, GRAP mRNA and protein were abnormally downregulated. Functionally, overexpression of GRAP drastically alleviated the proliferative and invasive ability of PAH HPASMCs through inhibition of the Ras/ERK signaling pathway in vitro and in vivo. In addition, METTL14 (methyltransferase-like 14) and the m6A binding protein YTHDF2 were significantly increased in PAH. Moreover, we found that m6A-modified GRAP mRNA was recognized by YTHDF2 to mediate the degradation. GRAP expression was consistently negatively correlated with METTL14 and YTHDF2 in vivo and in vitro. Taken together, for the first time, our findings highlight the function and therapeutic target value of GRAP and extend our understanding of the importance of RNA epigenetics in PAH.

Posttraumatic growth and rumination among parents of children with autism spectrum disorder: The mediating role of social support.

Although rumination and social support are regarded as essential predictors of posttraumatic growth (PTG), few studies have explored the associations among PTG, rumination, and social support in parents of children with autism spectrum disorder (ASD). This study examined whether social support mediates the relationship between rumination and PTG. Cross-sectional questionnaire data were collected from 385 parents of children with ASD from September 2019 to November 2020 by convenience sampling. Participants completed the Posttraumatic Growth Inventory, Event Related Rumination Inventory, and Social Support Rating Scale. Path analyses showed that subjective support partially mediates the relationship between deliberate rumination and PTG (ß = 0.073, P < 0.001), and indirect effects account for 15.30% of the total effects. In addition, a negative direct path was found between intrusive and PTG because of the suppression effect of subjective support (ß = -0.110, P < 0.01), and indirect effects accounted for 80% of the direct effects. For future studies, it underscores the essential role of subjective support and rumination in promoting PTG in parents of children with ASD.

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension.

Objective: Regulatory T cells (Tregs) are critical immune modulators to maintain immune homeostasis and limit pulmonary hypertension (PH). This study was aimed to identify Treg-related genes (TRGs) in PH. Methods: The gene expression profile from lungs of PH patients was retrieved from the Gene Expression Omnibus (GEO) database. The abundance of Tregs was estimated by the xCell algorithm, the correlation of which with differentially expressed genes (DEGs) was performed. DEGs with a |Pearson correlation coefficient| >0.4 were identified as TRGs. Functional annotation and the protein-protein interaction (PPI) network were analyzed. A gene signature for 25 hub TRGs (TRGscore) was generated by a single sample scoring method to determine its accuracy to distinguish PH from control subjects. TRGs were validated in datasets of transcriptional profiling of PH cohorts and in lung tissues of experimental PH mice. Results: A total of 819 DEGs were identified in lungs of 58 PAH patients compared to that of 25 control subjects of dataset GSE117261. In total, 165 of all these DEGs were correlated with the abundance of Tregs and identified as TRGs, with 90 upregulated genes and 75 downregulated genes compared to that of control subjects. The upregulated TRGs were enriched in negative regulation of multiple pathways, such as cAMP-mediated signaling and I-kappaB kinase/NF-kappaB signaling, and regulated by multiple genes encoding transcriptional factors including HIF1A. Furthermore, 25 hub genes categorized into three clusters out of 165 TRGs were derived, and we identified 27 potential drugs targeting 10 hub TRGs. The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7). Among them, 10 genes including NCF2, MNDA/Ifi211, HCK, FGR, CSF3R, AQP9, S100A8, G6PD/G6pdx, PGD, and TXNRD1 were significantly reduced in lungs of severe PH patients of dataset GSE24988 as well as in lungs of hypoxic PH mice compared to corresponding controls. Conclusion: Our finding will shed some light on the Treg-associated therapeutic targets in the progression of PH and emphasize on TRGscore as a novel indicator for PH.

Posttraumatic growth and postpartum depression in women after childbirth: The moderating role of postpartum negative life events.

AIM: This study aimed to investigate the implications of postpartum negative life events on postpartum depression and posttraumatic growth in women after childbirth. METHODS: A sample of 280 postpartum women at a level III hospital in China provided data on postpartum depression, negative life events, and posttraumatic growth with a cross-sectional design. RESULTS: The scores of both postpartum depression and negative life events exhibited a quadratic correlation with posttraumatic growth in women after childbirth, and negative life events significantly moderated the associations between depression and overall posttraumatic growth and its three dimensions: personal strength, spirit change, and relating to others. CONCLUSIONS: Women can experience positive psychological growth after childbirth, and this study provides new evidence of an interaction between postpartum depression and negative life events in the prediction of psychological growth, highlighting the moderating role of negative life events. This study could help direct mental health professionals to target interventions that provide more psychological support to reduce the impact of depression and negative life events, which will be conducive to improving women's psychological growth.

Metastatic Transition of Pancreatic Ductal Cell Adenocarcinoma Is Accompanied by the Emergence of Pro-Invasive Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) are now appreciated as key regulators of cancer metastasis, particularly in cancers with high stromal content, e.g., pancreatic ductal cell carcinoma (PDAC). However, it is not yet well understood if fibroblasts are always primed to be cooperative in PDAC transition to metastasis, if they undergo transformation which ensures their cooperativity, and if such transformations are cancer-driven or intrinsic to fibroblasts. We performed a fibroblast-centric analysis of PDAC cancer, as it transitioned from the primary site to trespass stromal compartment reaching the lymph node using published single-cell RNA sequencing data by Peng et al. We have characterized the change in fibroblast response to cancer from a normal wound healing response in the initial stages to the emergence of subclasses with myofibroblast and inflammatory fibroblasts such as signatures. We have previously posited "Evolved Levels of Invasibility (ELI)", a framework describing the evolution of stromal invasability as a selected phenotype, which explains the large and correlated reduction in stromal invasion by placental trophoblasts and cancer cells in certain mammals. Within PDAC samples, we found large changes in fibroblast subclasses at succeeding stages of PDAC progression, with the emergence of specific subclasses when cancer trespasses stroma to metastasize to proximal lymph nodes (stage IIA to IIB). Surprisingly, we found that the initial metastatic transition is accompanied by downregulation of ELI-predicted pro-resistive genes, and the emergence of a subclass of fibroblasts with ELI-predicted increased invasibility. Interestingly, this trend was also observed in stellate cells. Using a larger cohort of bulk RNAseq data from The Cancer Genome Atlas for PDAC cancers, we confirmed that genes describing this emergent fibroblast subclass are also correlated with lymph node metastasis of cancer cells. Experimental testing of selected genes characterizing pro-resistive and pro-invasive fibroblast clusters confirmed their contribution in regulating stromal invasability as a phenotype. Our data confirm that the complexity of stromal response to cancer is really a function of stage-wise emergence of distinct fibroblast clusters, characterized by distinct gene sets which confer initially a predominantly pro-resistive and then a pro-invasive property to the stroma. Stromal response therefore transitions from being tumor-limiting to a pro-metastatic state, facilitating stromal trespass and the onset of metastasis.

Animal models of pulmonary hypertension due to left heart disease.

Pulmonary hypertension due to left heart disease (PH-LHD) is regarded as the most prevalent form of pulmonary hypertension (PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease (LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.