Biomarker and transcriptomics profiles of serum selenium concentrations in patients with heart failure are associated with immunoregulatory processes.

BACKGROUND: Low selenium concentrations are associated with worse outcomes in heart failure (HF). However, the underlying pathophysiologic mechanisms remain incompletely understood. Therefore, we aimed to contrast serum selenium concentrations to blood biomarker and transcriptomic profiles in patients with HF. METHODS: Circulating biomarkers, whole blood transcriptomics and serum selenium measurements in a cohort of 2328 patients with HF were utilized. Penalized linear regression and gene expression analysis were used to assess biomarker and transcriptomics profiles, respectively. As a proof-of-principle, potential causal effects of selenium on excreted cytokines concentrations were investigated using human peripheral blood mononuclear cells (PBMCs). RESULTS: Mean selenium levels were 60.6 µg/L in Q1 and 122.0 µg/L in Q4. From 356 biomarkers and 20 clinical features, the penalized linear regression model yielded 44 variables with <5 % marginal false discovery rate as predictors of serum selenium. Biomarkers associated positively with selenium concentrations included: epidermal growth factor receptor (EGFR), IFN-gamma-R1, CD4, GDF15, and IL10. Biomarkers associated negatively with selenium concentrations included: PCSK9, TNFSF13, FGF21 and PAI. Additionally, 148 RNA transcripts were found differentially expressed between high and low selenium status (Padj.<0.05; log-fold-change<|0.25|). Enrichment analyses of the selected biomarkers and RNA transcripts identified similar enriched processes, including regulation processes of leukocyte differentiation and activation, as well as cytokines production. The mRNA expression of two selenoproteins (MSRB1 and GPX4) were strongly correlated with serum selenium, while GPX4, SELENOK, and SELENOS were associated with prognosis. In the in-vitro setting, PBMCs supplemented with selenium showed significantly lower abundance of several (pro-)inflammatory cytokines. CONCLUSION: These data suggest that immunoregulation is an important mechanism through which selenium might have beneficial roles in HF. The beneficial effects of higher serum selenium concentrations are likely because of global immunomodulatory effects on the abundance of cytokines. MSRB1 and GPX4 are potential modulators of and should be pursued in future research.

Attitudes and willingness to pay for clean heating by typical households: a case study of rural areas in Yongcheng City, Henan Province, China.

Understanding households' attitudes and willingness to pay (WTP) for clean heating can provide a scientific basis for decision-makers to assess the potential to develop clean heating, choose heating methods, and formulate subsidy standards in the region. In this paper, the double-bounded dichotomous contingent valuation method-modified by the spike model-was used to better estimate the actual WTP of households through a sample survey of 456 households in rural areas of Yongcheng City, China, in 2021. The factors influencing attitudes and WTP were examined to reveal mechanisms of accepting clean heating. The results showed that 94.96% of households were willing to pay for clean heating. The annual WTP was 1071 yuan per household, more than eight times the current heating cost. Factors that affect clean heating attitudes do not necessarily affect the WTP. Specifically, gender, length of time spent living at home, and family income had significant influences on WTP, whereas the educational level, adaptive perceptions in relation to environmental perceptions, and the recognition variables for gender equality in energy consumption had a significant impact on attitudes. It is worth noting that elderly people and females were identified as vulnerable groups in the implementation of clean heating.

The Perception of the National Traceability Platform among Small-Scale Tea Farmers in Typical Agricultural Areas in Central China.

As one of the key technologies to ensure the safety of agricultural products, the national traceability platform is being widely promoted in China. However, it has not yet been widely adopted among farmers, especially small-scale farmers. Farmers are both producers and direct participants in the traceability of agricultural products. Their perception directly affects the effectiveness of the promotion of the national traceability platform. This study explores the perception of the national traceability platform among small-scale tea farmers in typical agricultural areas in central China. This research employed Q methodology, an approach that integrates both qualitative and quantitative data allowing individuals' subjective understandings of a specific topic to be studied. The Q-sort procedure was performed in the field with 16 small-scale tea farmers. Next, Q-factor analyses were conducted using the Ken-Q analysis. The results show that small-scale tea farmers have different perceptions of the national traceability platform. Their main characteristics are active participation, resistant participation, risk aversion, and being driven by pressure. These four categories covered 52% of the perceived variance. Meanwhile, there is also a degree of internal consistency in the perception of small-scale tea farmers. Specifically, they are all concerned that participating in the national traceability platform may increase the cost and risk of cultivation and that it is difficult to obtain support from agricultural technicians. Therefore, understanding the perceptions of tea farmers of the national traceability platform is the premise for formulating effective promotion policies. Our research sheds light on the decision-making mechanisms for small-scale tea farmers to participate in national traceability platforms, further expanding the scope of current research on farmer behavior. This research has reference significance for promoting national traceability platforms in China and other countries around the world.

The psychological process and emotional cognition of children's tourism experiences in Chinese family culture.

The family cultural environment affects children's cognitive development and socialization processes, and different family cultural environments lead to differences in children's tourism experiences. The current research on children's tourism experiences demands a shift from the families' perspective to that of children's perspective. In response to this, grounded on the cognitive development theory, this paper, from the perspective of children's memorable parent-child tourism experience, uses 321 children's drawings to project the tourism elements, people, activities, scenes, and colors that children perceive from travel, reveals the main cognitive contents of children's parent-child tourism experiences. Furthermore, this paper analyzes the influence of family cultural background on children's tourism experiences through interviews with children. Our results show that with the growth of age, children's perception of elements changes from the macro level to the micro level, and the contents they perceive change from concrete to abstract. In addition, children have an acute perception of people and are impressed by novel activities during travel. They adapt well to changes in travel scenes and prefer bright and vibrant colors during trips. Therefore, we recommend the design of appropriate tourism products that combine the characteristics of children's experiences when offering parent-child travel programs, as well as upgrading the market of parent-child tourism experiences through novel activities.

Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke.

BACKGROUND: Human adipose-derived stem cells (hADSCs) have been demonstrated to be a promising autologous stem cell source for treating various neuronal diseases. Our study indicated that hADSCs could be induced into neuron-like cells in a stepwise manner that are characterized by the positive expression of MAP2, SYNAPSIN 1/2, NF-200, and vGLUT and electrophysiological activity. We first primed hADSCs into neuron-like cells (hADSC-NCs) and then intracerebrally transplanted them into MCAO reperfusion mice to further explore their in vivo survival, migration, integration, fate commitment and involvement in neural circuit rebuilding. RESULTS: The hADSC-NCs survived well and transformed into MAP2-positive, Iba1- or GFAP-negative cells in vivo while maintaining some proliferative ability, indicated by positive Ki67 staining after 4 weeks. hADSC-NCs could migrate to multiple brain regions, including the cortex, hippocampus, striatum, and hypothalamus, and further differentiate into mature neurons, as confirmed by action potential elicitation and postsynaptic currents. With the aid of a cell suicide system, hADSC-NCs were proven to have functionally integrated into the hippocampal memory circuit, where they contributed to spatial learning and memory rescue, as indicated by LTP improvement and subsequent GCV-induced relapse. In addition to infarction size shrinkage and movement improvement, MCAO-reperfused mice showed bidirectional immune modulation, including inhibition of the local proinflammatory factors IL-1α, IL-1ß, IL-2, MIP-1ß and promotion proinflammatory IP-10, MCP-1, and enhancement of the anti-inflammatory factors IL-15. CONCLUSION: Overall, hADSC-NCs used as an intermediate autologous cell source for treating stroke can rebuild hippocampus neuronal circuits through cell replacement.

Roles of Exosomes from Mesenchymal Stem Cells in Treating Osteoarthritis.

Exosomes are small extracellular vesicles (EVs) with a diameter of 50-150 nm that play important roles in cell-to-cell communication through transportation of proteins, microRNAs, lncRNAs, and mRNAs. Some components, such as miRNAs, have been proven to be involved in inflammation regulation. Osteoarthritis (OA) is a progressive disease resulting in articular cartilage degeneration and subchondral bone deficiency. Complicated relationships between the breakdown of extracellular matrix and inflammation make it difficult to recover thoroughly. Current studies reported that exosomes secreted by mesenchymal stem cells (MSCs) can change disease evolution and protect the cartilage matrix in OA. In addition, exosomes obtained from human adipose derived stem cells downregulate inflammation and oxidative stress, which might mediate antisenescence in OA. The goal of this review is to describe and summarize the role of mesenchymal stem cell (MSC)-derived exosomes in OA, focusing on their potential mechanism and possible therapeutic strategies.

Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses.

Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA sequencing (scRNA-seq) at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA). Computational analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells (ILC2s). Inflammation induced the expression of exon 5 of Calca, which encodes the alpha-calcitonin gene-related peptide (α-CGRP), in intestinal KLRG1+ ILC2s. α-CGRP antagonized KLRG1+ ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of α-CGRP increased the proportion of intestinal KLRG1+ ILC2s. Our work highlights a model where α-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery.

Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury.

Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed. With this protocol hADSCs could be converted into electrophysiologically active motoneuron-like cells (hADSC-MNs), which expressed both a cohort of pan neuronal markers and motor neuron specific markers. Moreover, after being primed for neuronal differentiation with RA/SHH, hADSCs were transplanted into SCI mouse model and they survived, migrated, and integrated into injured site and led to partial functional recovery of SCI mice. When ablating the transplanted hADSC-MNs harboring HSV-TK-mCherry overexpression system with antivirial Ganciclovir (GCV), functional relapse was detected by motor-evoked potential (MEP) and BMS assays, implying that transplanted hADSC-MNs participated in rebuilding the neural circuits, which was further confirmed by retrograde neuronal tracing system (WGA). GFP-labeled hADSC-MNs were subjected to whole-cell patch-clamp recording in acute spinal cord slice preparation and both action potentials and synaptic activities were recorded, which further confirmed that those pre-conditioned hADSCs indeed became functionally active neurons in vivo. As well, transplanted hADSC-MNs largely prevented the formation of injury-induced cavities and exerted obvious immune-suppression effect as revealed by preventing astrocyte reactivation and favoring the secretion of a spectrum of anti-inflammatory cytokines and chemokines. Our work suggests that hADSCs can be readily transformed into MNs in vitro, and stay viable in spinal cord of the SCI mouse and exert multi-therapeutic effects by rebuilding the broken circuitry and optimizing the microenvironment through immunosuppression.

Corrigendum: The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

[This corrects the article DOI: 10.3389/fimmu.2017.01723.].

Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus.

The onset of hepatic disorders in patients with systemic lupus erythematosus (SLE) is frequent; however, the etiology and liver pathogenesis of SLE remain unknown. In the present study, the role of hepatic deposited immunoglobulin G (IgG) in SLE-derived liver damage was investigated. From a retrospective analysis of the medical records of 404 patients with lupus and from experimental studies on mice models, we found that liver dysfunction is common in SLE and liver damage with IgG deposition spontaneously develops in lupus-prone mice. Liver injury was recreated in mice by injecting IgG from lupus serum intrahepatically. The inflammation intensity in the liver decreased with IgG depletion and the lupus IgG-induced liver inflammation in FcγRIII-deficient mice was comparatively low; while, inflammation was increased in FcγRIIb-deficient mice. Macrophages, Kupffer cells, natural killer cells, and their products, but not lymphocytes, are required for the initiation of SLE-associated liver inflammation. Blocking IgG signaling using a spleen tyrosine kinase (Syk) inhibitor suppressed the liver damage. Our findings provided evidence of spontaneously established liver damage in SLE. They also suggested that hepatic-deposited lupus IgG is an important pathological factor in the development of liver injury and that hepatic inflammation is regulated by the Syk signaling pathway. Thus, Syk inhibition might promote the development of a therapeutic strategy to control liver damage in patients with SLE.

The role of neutrophils in skin damage induced by tissue-deposited lupus IgG.

Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Neutrophils are crucial effector cells in the immune system but the significance of neutrophils in the pathogenesis of SLE is not clear. This study is to explore the role of neutrophils in the skin damage of SLE. We used lupus-prone mice and a C57BL/6 mouse model of lupus serum IgG-induced skin inflammation to investigate the role of neutrophils in skin damage of SLE. We found that a few neutrophils infiltrated the inflammatory sites of skin in lupus-prone mice and the lupus-IgG-induced skin damage mouse model. Depletion of neutrophils did not affect the development of skin inflammation caused by lupus IgG, and lupus IgG can induce apoptosis of neutrophils. The apoptosis of neutrophils induced by lupus IgG is related to FcγRIII and Fas/Fas ligand pathways. Our study indicates that neutrophils are not major contributors in the skin damage caused by tissue-deposited lupus IgG but death of neutrophils caused by lupus IgG may provide a resource of a large amount of autoantigens in SLE.

The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum IgG.

Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Estrogen may affect the onset and development of SLE through its receptor. In this study, we investigated the role of estrogen membrane receptor G protein-coupled estrogen receptor 1 (GPER1) in skin injury of SLE. We found that skin injury induced by SLE serum was more severe in female mice and required monocytes. Estrogen promoted activation of monocytes induced by lupus IgG through the membrane receptor GPER1 which was located in lipid rafts. Blockade of GPER1 and lipid rafts reduced skin inflammation induced by SLE serum. The results we obtained suggest that GPER1 plays an important role in the pathogenesis of skin inflammation induced by lupus IgG and might be a therapeutic target in skin lesions of patients with SLE.

Skin inflammation induced by lupus serum was inhibited in IL-1R deficient mice.

Skin inflammation induced by lupus serum is a useful tool to investigate the pathogenesis of lupus skin injury. IL-1 is a proinflammatory cytokine, and its role in lupus skin lesion is still unclear. We determined the role of IL-1 in lupus skin injury by using gene deficient mice. We found that skin inflammation induced by lupus serum was significantly reduced in IL-1R deficient mice and caspase-1 deficient mice. IL-1R deficiency did not affect the expression of FcγRI (CD64), FcγRII (CD32) and MHC class II (CD74) induced by lupus serum. IL-1R deficiency reduced the lipid raft clustering, and decreased expression of MCP-1 and TNFα in monocytes. Keratinocyte proliferation induced by lupus serum was significantly decreased in TNFα deficient mice. Our findings indicate that IL-1 plays an important role in skin lesions of SLE. This study suggests that IL-1 is a therapeutic target in skin lesions of SLE.