Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells.

In this editorial, we offer our perspective on the groundbreaking study entitled "Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells", recently published in World Journal of Stem Cells. Despite over three decades of research on the clinical application of mesenchymal stem cells (MSCs), only a few therapeutic products have made it to clinical use, due to multiple preclinical and clinical challenges yet to be addressed. The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics, which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs. As we delve deeper into the intricacies of pretreatment methodologies, we anticipate a transformative shift in the landscape of MSC-based therapies, ultimately contributing to improved patient outcomes and advancing the field as a whole.

Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway.

The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Expression Analysis of circRNAs in Human Adipogenesis.

Purpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis. Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR). Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs. Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.

Pyroptosis-related gene signature elicits immune response in rosacea.

Rosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis-related rosacea aggravations. In this study, we evaluated the pyroptosis-related patterns of rosacea by consensus clustering analysis of 45 ferroptosis-related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis-mediated immune response in rosacea using GSE65914 dataset. The co-co-work between PRGs and WGCNA-revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi-transcriptomic and experiment analysis. Based on this, three distinct pyroptosis-related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune-related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune-related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis-immune co-work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.

PANoptosis signaling enables broad immune response in psoriasis: From pathogenesis to new therapeutic strategies.

Background: Accumulating evidence suggests that regulated cell death, such as pyroptosis, apoptosis, and necroptosis, is deeply involved in the pathogenesis of psoriasis. As a newly recognized form of systematic cell death, PANoptosis is involved in a variety of inflammatory disorders through amplifying inflammatory and immune cascades, but its role in psoriasis remains elusive. Objectives: To reveal the role of PANoptosis in psoriasis for a potential therapeutic strategy. Methods: Multitranscriptomic analysis and experimental validation were used to identify PANoptosis signaling in psoriasis. RNA-seq and scRNA-seq analyses were performed to establish a PANoptosis-mediated immune response in psoriasis, which revealed hub genes through WGCNA and predicted disulfiram as a potential drug. The effect and mechanism of disulfiram were verified in imiquimod (IMQ)-induced psoriasis. Results: Here, we found a highlighted PANoptosis signature in psoriasis patients through multitranscriptomic analysis and experimental validation. Based on this, two distinct PANoptosis patterns (non/high) were identified, which were the options for clinical classification. The high-PANoptosis-related group had a higher response rate to immune cell infiltration (such as M1 macrophages and keratinocytes). Subsequently, WGCNA showed the hub genes (e.g., S100A12, CYCS, NOD2, STAT1, HSPA4, AIM2, MAPK7), which were significantly associated with clinical phenotype, PANoptosis signature, and identified immune response in psoriasis. Finally, we explored disulfiram (DSF) as a candidate drug for psoriasis through network pharmacology, which ameliorated IMQ-mediated psoriatic symptoms through antipyroptosis-mediated inflammation and enhanced apoptotic progression. By analyzing the specific ligand-receptor interaction pairs within and between cell lineages, we speculated that DSF might exert its effects by targeting keratinocytes directly or targeting M1 macrophages to downregulate the proliferation of keratinocytes. Conclusions: PANoptosis with its mediated immune cell infiltration provides a roadmap for research on the pathogenesis and therapeutic strategies of psoriasis.

Mesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future Opportunity.

Type 1 Diabetes (T1D) is characterized by hyperglycemia, and caused by a lack of insulin secretion. At present there is no cure for T1D and patients are dependent on exogenous insulin for lifelong, which seriously affects their lives. Mesenchymal stem cells (MSCs) can be differentiated to ß cell-like cells to rescue the secretion of insulin and reconstruct immunotolerance to preserve the function of islet ß cells. Due to the higher proportion of children and adolescents in T1D patients, the efficacy and safety issue of the application of MSC's transplant in T1D was primarily demonstrated and identified by human clinical trials in this review. Then we clarified the mechanism of MSCs to relieve the symptom of T1D and found out that UC-MSCs have no obvious advantage over the other types of MSCs, the autologous MSCs from BM or menstrual blood with less expanded ex vivo could be the better choice for clinical application to treat with T1D through documentary analysis. Finally, we summarized the advances of MSCs with different interventions such as genetic engineering in the treatment of T1D, and demonstrated the advantages and shortage of MSCs intervened by different treatments in the transplantation, which may enhance the clinical efficacy and overcome the shortcomings in the application of MSCs to T1D in future.

Therapeutic role of growth factors in treating diabetic wound.

Wounds in diabetic patients, especially diabetic foot ulcers, are more difficult to heal compared with normal wounds and can easily deteriorate, leading to amputation. Common treatments cannot heal diabetic wounds or control their many complications. Growth factors are found to play important roles in regulating complex diabetic wound healing. Different growth factors such as transforming growth factor beta 1, insulin-like growth factor, and vascular endothelial growth factor play different roles in diabetic wound healing. This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds. Further, some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors. The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

HSF1 Alleviates Brain Injury by Inhibiting NLRP3-Induced Pyroptosis in a Sepsis Model.

Background: Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient's prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective: NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods: In this study, we used wild-type mice and hsf1 -/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results: The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1 -/- mouse model compared to hsf1 +/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion: These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.

Comprehensive Analysis of circRNA Expression Profiles in Human Brown Adipose Tissue.

Purpose: Brown adipose tissue (BAT) can rapidly generate heat and improve energy metabolism. Circular RNAs (circRNAs) are cellular endogenous non-coding RNAs, which can regulate the development and progress of different diseases. However, the role of circRNAs in human BAT is not fully understood. Here, we analyzed the differentially expressed circRNAs (DECs) in human BAT, as well as in white adipose tissue (WAT), and identified new biomarkers of BAT. Patients and Methods: Three human BAT and three human subcutaneous WAT samples were selected, and circRNA microarray was performed. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of six circRNAs. Finally, the functional analysis was performed by bioinformatics. Results: Compared to WAT, 152 upregulated circRNAs and 201 downregulated circRNAs were identified in BAT. The DECs were further subjected to GO and KEGG enrichment analysis. Several circRNAs, for example, hsa_circ_0006168, hsa_circ_26337 and hsa_circ_0007507 were found upregulated and hsa_circ_0030162 was found downregulated in human BAT compared to WAT. Conclusion: This study profiles the circRNA expression in human BAT and WAT, and suggests hsa_circ_0006168, hsa_circ_26337, hsa_circ_0007507, and hsa_circ_0030162 as novel biomarkers for human BAT.

The vicious circle of UHRF1 down-regulation and KEAP1/NRF2/HO-1 pathway impairment promotes oxidative stress-induced endothelial cell apoptosis in diabetes.

BACKGROUND: Oxidative stress is recognized as a key factor in the induction of endothelial dysfunction in diabetes. However, the specific mechanisms have not been fully elucidated. We herein hypothesized that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) might have a role in oxidative stress-induced endothelial cell (EC) apoptosis in diabetes. METHODS: Western blot, qPCR, wound healing assay, apoptosis assay, reactive oxygen species (ROS) detection, dual-luciferase reporter assay, methylation-specific PCR, bisulfite sequencing PCR and chromatin immunoprecipitation assay were performed. RESULTS: UHRF1 expression levels were significantly decreased in endothelial colony-forming cells derived from peripheral blood of participants with type 2 diabetes compared with individuals without diabetes. ECs treated with high glucose, palmitate or hydrogen peroxide in vitro also exhibited decreased UHRF1 protein levels. Silencing of UHRF1 led to decreased migration ability and increased apoptosis and ROS production in ECs, which might be related to impaired Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2)/haeme oxygenase-1 pathway. Mechanistically, UHRF1 is closely implicated in epigenetic regulation of chromatin modification status at KEAP1 genomic locus via histone acetylation. NRF2 down-regulation in turn inhibits UHRF1 protein level, which might be due to increased ROS generation. CONCLUSION: Diabetes-induced oxidative stress can mediate down-regulation of UHRF1, which enhances ROS production by regulating KEAP1/p-NRF2 pathway through histone acetylation and might also form a self-perpetuating feedback loop with KEAP1/p-NRF2 to further promote oxidative stress-induced apoptosis of ECs in diabetes.

Current research and clinical trends in rosacea pathogenesis.

Background: Rosacea is a common and complex chronic inflammatory skin disorder, the pathophysiology and etiology of which remain unclear. Recently, significant new insights into rosacea pathogenesis have enriched and reshaped our understanding of the disorder. A systematic analysis based on current studies will facilitate further research on rosacea pathogenesis. Objective: To establish an international core outcome and knowledge system of rosacea pathogenesis and develop a challenge, trend and hot spot analysis set for research and clinical studies on rosacea using bibliometric analysis and data mining. Methods: A search of the WoS, and PubMed, MEDLINE, Embase and Cochrane collaboration databases was conducted to perform visual bibliometric and data analysis. Results: A total of 2,654 studies were used for the visualization and 302 of the 6,769 outcomes for data analysis. It reveals an increased trend line in the field of rosacea, in which its fast-growing pathogenesis attracted attention closely related to risk, comorbidity and therapeutic strategies. The rosacea pathogenesis has undergone the great development on immunology, microorganisms, genes, skin barriers and neurogenetics. The major of studies have focused on immune and microorganisms. And keyword visualization and data analyses demonstrated the cross-talk between cells or each aspect of pathogenesis, such as gene-gene or gene-environment interactions, and neurological mechanisms associated with the rosacea phenotype warrant further research. Limitations: Inherent limitations of bibliometrics; and reliance on research and retrospective studies. Conclusions: The understanding of rosacea's pathogenesis has been significantly enhanced with the improved technology and multidisciplinary integration, but high-quality, strong evidence in favor of genomic and neurogenic requires further research combined with a better understanding of risks and comorbidities to guide clinical practice.

Peripheral Blood circRNA Microarray Profiling Identities hsa_circ_0001831 and hsa_circ_0000867 as Two Novel circRNA Biomarkers for Early Type 2 Diabetic Nephropathy.

Purpose: Type 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN. Patients and Methods: Twenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools. Results: There were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN. Conclusion: Our study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.

Estimating accumulation rates and health risks of PAHs in residential soils of metropolitan cities.

Predicting temporal changes in PAH concentrations in urban soils and their corresponding health risk is essential for developing appropriate management measures to prevent those risks. Concentrations of PAHs in soils of residential areas with different building ages in three metropolitan cities were determined to estimate the accumulation rates of PAHs in soil. The mean concentrations of total PAHs (∑PAHs) were 1297 ng/g in Shanghai, 865 ng/g in Beijing, and 228 ng/g in Shenzhen. The primary sources of the PAHs were traffic and coal combustion for industrial activity and space heating. The high PAH concentrations in Shanghai were attributed to the relatively high average building age of the sampled residential areas and the low annual temperature in the city. The overall annual accumulation rates of PAHs in the soils were estimated from linear regressions between the PAH concentrations and building age of the residential areas. The annual accumulation rate of PAHs in the soils was 64.7 ng/g in Beijing, 24.2 ng/g in Shanghai, and 3.3 ng/g in Shenzhen. The higher rate in Beijing was due to the higher intensity of PAH emissions and the lower temperature. The regression estimations suggest that health risks posed by PAHs in residential soils of the metropolitan cities increase considerably with time.

Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that attacks pancreatic ß-cells, leading to the destruction of insulitis-related islet ß-cells. Islet ß-cell transplantation has been proven as a curative measure in T1DM. However, a logarithmic increase in the global population with diabetes, limited donor supply, and the need for lifelong immunosuppression restrict the widespread use of ß-cell transplantation. Numerous therapeutic approaches have been taken to search for substitutes of ß-cells, among which stem cell transplantation is one of the most promising alternatives. Stem cells have demonstrated the potential efficacy to treat T1DM by reconstitution of immunotolerance and preservation of islet ß-cell function in recent research. cGMP-grade stem cell products have been used in human clinical trials, showing that stem cell transplantation has beneficial effects on T1DM, with no obvious adverse reactions. To better achieve remission of T1DM by stem cell transplantation, in this work, we explain the progression of stem cell transplantation such as mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), and bone marrow hematopoietic stem cells (BM-HSCs) to restore the immunotolerance and preserve the islet ß-cell function of T1DM in recent years. This review article provides evidence of the clinical applications of stem cell therapy in the treatment of T1DM.

Hyaluronic Acid Facilitates Angiogenesis of Endothelial Colony Forming Cell Combining With Mesenchymal Stem Cell via CD44/ MicroRNA-139-5p Pathway.

Stem cells and progenitor cells have been identified as potential new therapeutic options for severe limb ischemia to induce angiogenesis, and hyaluronic acid (HA) is commonly applied as a biomaterial in tissue engineering. However, the efficiency of HA combined with human umbilical cord blood-derived endothelial colony forming cells (ECFCs) and human umbilical-derived mesenchymal stem cells (MSCs) on angiogenesis is unclear. In the present study, we showed that HA promoted angiogenesis induced by MSCs-ECFCs in Matrigel plugs and promoted blood perfusion of murine ischemic muscles. Laser confocal microscopy revealed that human-derived cells grew into the host vasculature and formed connections, as shown by mouse-specific CD31+/human-specific CD31+ double staining. In vitro assays revealed that HA supported cell proliferation and migration, enhanced CD44 expression and reduced microRNA (miR)-139-5p expression. Further analysis revealed that miR-139-5p expression was negatively regulated by CD44 in ECFCs. Flow cytometry assays showed that HA increased CD31 positive cells proportion in MSC-ECFC and could be reversed by miR-139-5p mimics transfection. Moreover, the improvement of MSC-ECFC proliferation and migration induced by HA could be blocked by upregulation of miR-139-5p expression. In conclusion, HA facilitates angiogenesis of MSCs-ECFCs, and this positive effect be associated with activation of the CD44/miR-139-5p pathway, providing a promising strategy for improving severe limb ischemia.

Estimation of the accumulation rates and health risks of heavy metals in residential soils of three metropolitan cities in China.

Heavy metal concentrations in urban soils are likely to increase over time because of continuous urbanization and heavy metal emissions. To estimate the accumulation rates of heavy metals in urban soils, we collected soil samples from residential areas with different building ages in the metropolitan cities of Shanghai, Shenzhen, and Beijing, China. Heavy metal concentrations in the soils varied among the cities and were primarily affected by soil parent material and the intensity of anthropogenic sources. Regression analyses revealed that the accumulation rates of Cd and Cu in the soils ranged from 0.0034 to 0.0039 mg/(kg•year) and 0.343 to 0.391 mg/(kg•year), respectively, and were similar across the three cities, while accumulation rates of Zn and Pb in Shanghai were higher than those in Shenzhen and Beijing. The higher accumulation rates of Zn and Pb in Shanghai can be explained by differences in city history and industrial structures among the cities. Residential soils with high health risks posed by the heavy metals were mostly collected from old towns of Shanghai because of high Pb content in the areas. Although recent urbanization resulted in elevated concentrations of Cd, Cu, Zn, and Pb in the residential soils, the effect on the total health risks of residents exposed to the soils was negligible.

Maternal plasma serotonin level not suitable as postpartum depression diagnostic biomarker: Results from a prospective cohort study.

BACKGROUND: Whether plasma serotonin (5-HT) levels could be a biomarker for postpartum depression (PPD) diagnosis is under dispute. METHODS: A total of 979 of pregnant women without antenatal depression at the time of delivery (TD) were enrolled and followed up at six weeks postpartum (SWP) in Changsha, China. The odds ratio (OR) and 95% confidence interval (CI) for plasma 5-HT level at TD, at SWP, changes in 5-HT, and risk of PPD and deterioration in EPDS scores at SWP were estimated by Logistic regressions. Restricted cubic spline (RCS) functions were also used to assess the dose-response relationships. RESULTS: The 6-week cumulative incidence of PPD was 12.05% (95%CI:10.08%, 14.26%). The average level of plasma 5-HT changed from 223.65 ± 131.47 ng/ml at TD to 216.43 ± 122.73 ng/ml at SWP, with an average change of -7.22 ± 96.54 ng/ml. Plasma 5-HT at TD was negatively correlated with EPDS score at TD and SWP (p < 0.05), as was the correlation between 5-HT at SWP and EPDS scores at SWP (p = 0.038). However, the changes in 5-HT were not associated with the EPDS score at SWP (p = 0.346). Neither plasma 5-HT level at TD nor changes in 5-HT was associated with PPD at SWP or deterioration in EPDS scores (p < 0.05). Plasma 5-HT at delivery had insignificant discriminatory power for diagnosing PPD and prediction of deterioration in EPDS scores (p ≥ 0.05). CONCLUSION: Plasma 5-HT level at delivery was associated with EPDS score at delivery and SWP, but not with PPD at SWP suggesting that plasma 5-HT is not suitable as PPD diagnostic biomarker.

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Distribution Characteristics and Risk Assessment of Heavy Metals in Soil and Street Dust with Different Land Uses, a Case in Changsha, China.

Rapid urbanization and industrialization have led to the accumulation of heavy metals in urban areas. The distribution and health risk of heavy metals in soil and street dust were studied by collecting the samples in pairs from different land uses in Changsha, China. The results showed that the average contents of the heavy metals Pb, Cd, Cu, Zn, Cr and Ni in the soil were 45.3, 0.69, 46.3, 220.4, 128.7 and 32.9 mg·kg-1, and the corresponding heavy metal contents in the street dust were 130.1, 3.9, 130.8, 667.2, 223.2, 50.5 mg·kg-1, respectively. The soils in the parks and roadsides have higher heavy metal contents than those in the residential and agricultural areas. The street dust collected from parks, roadsides and residential areas contained higher heavy metal contents than agricultural areas. Significant correlations were found between heavy metals, suggesting similar sources. However, most of the heavy metals in the soil were uncorrelated with those in the street dust. The contents of heavy metals in soil are the results of long-term pollution. Street dust is easily affected by natural or human disturbances, reflecting pollution emissions in a short period. The health risks posed by heavy metals in the soil are acceptable, but the street dust may threaten children's health, especially in residential areas. Pb, Cr and Cd are the main risk contributors. Reducing the emissions from industrial plants and traffic may reduce the risk of exposure to heavy metals in the street dust.