Nlrc3 signaling is indispensable for hematopoietic stem cell emergence via Notch signaling in vertebrates.

Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.

Assessment of the induced effect of selected iron hydroxysulfates biosynthesized using Acidithiobacillus ferrooxidans for biomineralization of acid mine drainage.

Soluble iron and sulfate in acid mine drainage (AMD) can be greatly removed through the formation of minerals facilitated by seed crystals. However, the difference in the effects of jarosite and schwertmannite as endogenous seed crystals to induce AMD mineralization remains unclear. This paper intends to study the effect of Fe2+ oxidation and Fe3+ mineralization in the biosynthesis of minerals using different addition amounts and methods of jarosite or schwertmannite. The results showed that the addition amount and method of different seed crystals had no effect on the Fe2+ bio-oxidation but would change the Fe3+ mineralization efficiency. With the same amount of seed crystals added, jarosite exhibited a higher capacity to promote Fe3+ mineralization than schwertmannite. Adding seed crystals before the initiation of Fe2+ oxidation (0 h) could significantly promote Fe3+ mineralization efficiency. With the increase of seed crystals, jarosite could not only shorten the time required for mineral synthesis but also improve the final mineral yield, whereas schwertmannite could only shorten the time required for mineral synthesis. When Fe2+ was completely oxidized to Fe3+ (48 h), the supplementary of jarosite could still effectively improve Fe3+ mineralization efficiency, but the addition of schwertmannite no longer affected the final mineralization degree.

Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells.

BACKGROUND: In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development. METHODS: In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development. Loss and gain-of-function strategies were applied to study the biological function of gmfg. Whole-mount in situ hybridization, confocal microscopy, flow cytometry, and western blotting were used to evaluate changes in the number of various hematopoietic cells and expression levels of cell proliferation, cell apoptosis and hematopoietic-related markers. RNA-seq was performed to screen signaling pathways responsible for gmfg deficiency-induced defects in HSPC initiation. The effect of gmfg on YAP sublocalization was assessed in vitro by utilizing HUVEC cell line. RESULTS: We took advantage of zebrafish embryos to illustrate that loss of gmfg impaired HSPC initiation and maintenance. In gmfg-deficient embryos, the number of hemogenic endothelium and HSPCs was significantly reduced, with the accompanying decreased number of erythrocytes, myelocytes and lymphocytes. We found that blood flow modulates gmfg expression and gmfg overexpression could partially rescue the reduction of HSPCs in the absence of blood flow. Assays in zebrafish and HUVEC showed that gmfg deficiency suppressed the activity of YAP, a well-established blood flow mediator, by preventing its shuttling from cytoplasm to nucleus. During HSPC initiation, loss of gmfg resulted in Notch inactivation and the induction of Notch intracellular domain could partially restore the HSPC loss in gmfg-deficient embryos. CONCLUSIONS: We conclude that gmfg mediates blood flow-induced HSPC maintenance via regulation of YAP, and contributes to HSPC initiation through the modulation of Notch signaling. Our findings reveal a brand-new aspect of gmfg function and highlight a novel mechanism for embryonic HSPC development.

Polypropylene microplastics affect the distribution and bioavailability of cadmium by changing soil components during soil aging.

Compared with the widespread and serious heavy metal contamination in soils, microplastic pollution has gained attention only recently. Little is known about how microplastics affect the distribution of heavy metals in soils, especially across soil components level. In this study, a 180-day soil aging experiment and soil density fractionation were performed to investigate the effect of polypropylene (PP) microplastics on the binding behavior of cadmium (Cd) to solid components, i.e. particulate organic matter, organo-mineral complexes (OMC), and mineral. Results showed addition of 2-10% microplastics in soils induced the decomposition of OMC fraction by 10.88-23.10%. Compared to the control, the content of dissolved organic carbon increased, and pH, humic substances, and soil organic matter decreased with microplastics. After 180d of aging, the content of Cd in OMC fraction increased by 17.92%, while microplastics made Cd contents decline by 10.01-19.75%. The impacts strongly depended on the dose and surface characteristic of microplastics. Overall, PP microplastics increased the concentration of bioavailable Cd in soils via decreasing soil retention of Cd by the OMC fraction. These findings based on the solid components level will provide a new perspective for understanding microplastics effects on soil systems and pollutants.

Exposure to the environmentally toxic pesticide maneb induces Parkinson's disease-like neurotoxicity in mice: A combined proteomic and metabolomic analysis.

Maneb is a typical dithiocarbamate fungicide that has been extensively used worldwide. Epidemiological evidence shows that exposure to maneb is an environmental risk factor for Parkinson's disease (PD). However, the mechanisms underlying maneb-induced neurotoxicity have yet to be elucidated. In this study, we exposed SH-SY5Y cells to maneb at environmentally relevant concentrations (0, 0.1, 5, 10 mg/L) and found that maneb dose-dependently decreased the cell viability. Furthermore, maneb (60 mg/kg) induced PD-like motor impairment in α-synuclein A53T transgenic mice. The results of tandem mass tag (TMT) proteomics and metabolomics studies of mouse brain and serum revealed significant changes in proteins and metabolites in the pathways involved in the neurotransmitter system. The omics results were verified by targeted metabolomics and Western blot analysis, which demonstrated that maneb induced disturbance of the PD-related pathways, including the phenylalanine and tryptophan metabolism pathways, dopaminergic synapse, synaptic vesicle cycle, mitochondrial dysfunction, and oxidative stress. In addition, the PD-like phenotype induced by maneb was attenuated by the asparagine endopeptidase (AEP) inhibitor compound #11 (CP11) (10 mg/kg), indicating that AEP may play a role in maneb-induced neurotoxicity. To the best of our knowledge, this is the first study to investigate the molecular mechanisms underlying maneb-induced PD-like phenotypes using multiomics analysis, which identified novel therapeutic targets for PD associated with pesticides and other environmental pollutants.

Effects of Chlorine Addition on Nitrogen Oxide Reduction and Mercury Oxidation over Selective Catalytic Reduction Catalysts.

The effect of chlorine on mercury oxidation and nitrogen oxides (NO x ) reduction over selective catalytic reduction (SCR) catalysts was investigated in this study. Commercial SCR catalysts achieved a high Hg0 oxidation efficiency when Cl2 was sprayed into the flue gas. Results indicated that an appropriate concentration of Cl2 was found to promote NO x reduction and Hg0 oxidation significantly. An optimal concentration of Cl2 (25 ppm) was found to significantly promote NO x reduction and Hg0 oxidation. Moreover, we studied the effects of Cl2 on NO x reduction and Hg0 oxidation over SCR catalysts under different concentrations of SO2. The SO2 poisoning effect was decreased by Cl2 when the SO2 concentration was low (below 1500 ppm). However, sulfate gradually covered the catalyst surface over time during the reaction, which limited the impact of Cl2. Finally, different sulfur-poisoned catalysts were examined in the presence of Cl2. The NO x reduction and Hg0 oxidation performances of sulfate-poisoned catalysts improved when Cl2 was added to the flue gas. Mechanisms for NO x reduction and Hg0 oxidation over fresh catalysts and sulfate-poisoned catalysts in the presence of Cl2 were proposed in this study. The mechanism of Cl2-influenced NO x reduction was similar to that for the NH3-SCR process. With Cl2 in the flue gas, the number of Brønsted active sites increased, which improved catalytic activity. Furthermore, Cl2 reoxidized V4+-OH to V5+=O and caused the NH3-SCR process to operate continuously. The Langmuir-Hinshelwood mechanism was followed for Hg0 oxidation by SCR catalysts when Cl2 was in the flue gas. Cl2 increased the number of Lewis active sites, and catalytic activity increased. Hg0 adsorbed on the surface of the catalysts and was then oxidized to HgCl2. Adding Cl2 to the flue gas increased the strength and number of acid sites on sulfate-poisoned catalysts.

Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steady-state blood using a polypeptide-forming 3D culture.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34+ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34+ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.

Characteristics and source-pathway of microplastics in freshwater system of China: A review.

China plays a key role in global plastic production, consumption and disposal, which arouses growing concern about microplastics (MPs) contamination in Chinese freshwater systems. However, few reviews have discussed the characteristics of MP pollution in whole freshwater systems at a national scale. In this review, we summarized the characteristics, sources and transport pathways of MPs in Chinese freshwater systems including surface water and sediment. Results showed that current research mainly focused on the middle and lower reaches of the Yangtze River and its tributaries, as well as lakes and reservoirs along the Yangtze River. Large-scale reservoirs, rivers and lakes located in densely populated areas usually showed higher abundances of MPs. The majority of MPs in Chinese surface water and sediment mainly consisted of polyethylene and polypropylene, and the most common morphologies were fibers and fragments. To identify the sources and pathways, we introduced the source-sink-pathway model, and found that sewage system, farmland and aquaculture area were the three most prevalent sinks in freshwater systems in China. The source-sink-pathway model will help to further identify the migration of MPs from sources to freshwater systems.

Removal of elemental mercury from flue gas using the magnetic attapulgite by Mn-Cu oxides modification.

Mercury pollution has become one of the most concerned environmental issues in the world because of its high toxicity, non-degradability, and bioaccumulation. Attapulgite adsorbents modified by magnetic manganese-copper (MnxCuy-MATP) were fabricated by co-precipitation and ultrasonic impregnation method, aiming at removing Hg0 from coal-fired flue gas. BET, SEM, XRD, VSM, and XPS were used to systematically explore the physical and chemical properties of the adsorbents, the effects of manganese and copper additions, reaction temperature, and various components in the flue gas on the efficiency of Hg0 removal were investigated. Mn8Cu5-MATP exhibited the optimal properties, and excessive copper loadings led to the aggregation of the active components. The efficiency of mercury removal can be effectively improved by NO and HCl regardless of the absence and presence of O2, because the NO+, NO3, NO2, and Cl* produced during the reaction can promote the adsorption and oxidation of Hg0. SO2 and H2O inhibited the oxidation of Hg0 because of the competitive adsorption at the active sites, while a large amount of sulfite and sulfate were formed to block the pores. However, the introduction of copper caused the sample to obtain SO2 resistance, which resulted in a mercury removal efficiency of 84.3% even under 1500 ppm SO2. In addition, after 5 cycles of adsorption and regeneration, Mn8Cu5-MATP can still maintain excellent Hg0 removal ability. The fabricated adsorbent can save the actual production cost and effectively improve the mercury removal efficiency in sulfur-containing flue gas.

Specific Blood Cells Derived from Pluripotent Stem Cells: An Emerging Field with Great Potential in Clinical Cell Therapy.

Widely known for self-renewal and multilineage differentiation, stem cells can be differentiated into all specialized tissues and cells in the body. In the past few years, a number of researchers have focused on deriving hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) as alternative sources for clinic. Existing findings demonstrated that it is feasible to obtain HSCs and certain mature blood lineages from PSCs, except for several issues to be addressed. This short review outlines the technologies used for hematopoietic differentiation in recent years. In addition, the therapeutic value of PSCs as a potential source of various blood cells is also discussed as well as its challenges and directions in future clinical applications.

Biomechanical cues as master regulators of hematopoietic stem cell fate.

Hematopoietic stem cells (HSCs) perceive both soluble signals and biomechanical inputs from their microenvironment and cells themselves. Emerging as critical regulators of the blood program, biomechanical cues such as extracellular matrix stiffness, fluid mechanical stress, confined adhesiveness, and cell-intrinsic forces modulate multiple capacities of HSCs through mechanotransduction. In recent years, research has furthered the scientific community's perception of mechano-based signaling networks in the regulation of several cellular processes. However, the underlying molecular details of the biomechanical regulatory paradigm in HSCs remain poorly elucidated and researchers are still lacking in the ability to produce bona fide HSCs ex vivo for clinical use. This review presents an overview of the mechanical control of both embryonic and adult HSCs, discusses some recent insights into the mechanisms of mechanosensing and mechanotransduction, and highlights the application of mechanical cues aiming at HSC expansion or differentiation.

Generation of an ELTD1 knockout human embryonic stem cell line by the iCRISPR/Cas9 system.

Human ELTD1 (Epidermal growth factor, latrophilin and seven-transmembrane domain-containing 1), an orphan G-protein-coupled receptor (GPCR) belonging to the adhesion GPCR family, has been reported as a novel regulator of angiogenesis and a potential anti-cancer therapeutic target. However, little is known about the function of ELTD1, especially its undiscovered ligands. In this experiment, an ELTD1 homozygous knockout human embryonic stem cell line, FAHZUe001-A, was generated by the iCRISPR/Cas9 system to achieve a deeper understanding of ELTD1. The FAHZUe001-A was confirmed with normal karyotype, typical undifferentiated morphology, pluripotency and trilineage differentiation potential in vitro.

Enhanced HSC-like cell generation from mouse pluripotent stem cells in a 3D induction system cocultured with stromal cells.

BACKGROUND: Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. METHODS: In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. RESULTS: The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. CONCLUSIONS: Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.

A critical review on the interactions of microplastics with heavy metals: Mechanism and their combined effect on organisms and humans.

Although individual toxicity of microplastics (MPs) to organism has been widely studied, limited knowledge is available on the interactions between heavy metals and MPs, as well as potential biological impacts from their combinations. The interaction between MPs and heavy metals may alter their environmental behaviors, bioavailability and potential toxicity, leading to ecological risks. In this paper, an overview of different sources of heavy metals on MPs is provided. Then the recent achievements in adsorption isotherms, adsorption kinetics and interaction mechanism between MPs and heavy metals are discussed. Besides, the factors that influence the adsorption of heavy metals on MPs such as polymer properties, chemical properties of heavy metals, and other environmental factors are also considered. Furthermore, potential combined toxic effects from MPs and heavy metals on organisms and human health are further summarized.

The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.

Investigation and probabilistic health risk assessment of trace elements in good sale lip cosmetics crawled by Python from Chinese e-commerce market.

A growing body of evidence suggests that the lip products are polluted by heavy metals, which would inevitably cause safety problems with long-term exposure, but few studies have focused on their deeper health risk assessments. This study sets out to identify the lip cosmetics in good sale from Chinese e-commerce market utilizing Python crawler and then explore the probabilistic health risks caused by 6 trace elements in 34 most popular lip cosmetics with Monte Carlo simulation. The results found that there was no obvious non-carcinogenic risk to humans. As for high users, the carcinogenic risk levels of Cr exceeded the acceptable risk recommended by USEPA, approximately 10% and 25% for lipsticks and lip glosses, respectively. Cr was regarded as the priority metal for risk control in the present study. Finally, it was recommended that the minimum use period limit for using up one lip product ranged from 0.54 months to 5.74 months. Overall, this study appears to be the first to conduct a probabilistic health risk assessment of trace elements in lip products, which would be of significance for policy makers to take effective strategies to minimize exposure health risk and contamination.

Removal of elemental mercury from flue gas using the magnetic Fe-containing carbon prepared from the sludge flocculated with ferrous sulfate.

The sewage sludge flocculated with ferrous sulfate (SFS) was prepared by one-step pyrolysis to obtain magnetic Fe-containing carbon. Results showed that only a small amount of FexOy as well as extremely weak magnetism were observed at pyrolysis temperatures of less than 500 °C. SFS tended to exhibit intensive agglomeration, leading to the drastic increase of the crystalline-phase particle size at high pyrolysis temperature. The optimal pyrolysis temperature is 700 °C, corresponding to the production of some sulfides, an optimal content of FexOy, and a suitable BET surface. Hg0 removal efficiency of SFS700 (SFS pyrolyzed at 700 °C) reached 80.7% at the reaction temperature of 125 °C. The presence of O2 and low concentration of SO2 enhanced the Hg0 removal, while the H2O vapor and high SO2 concentration inhibited it. Meanwhile, good resistance for the adsorbent to moderate concentrations of SO2 and H2O was observed. Moreover, the good magnetism performance is conducive to the recovery and utilization of the SFS700 in flue gas. Therefore, SFS can be used for Hg0 removal without any chemical modification after undergoing one-step pyrolysis and this study has guiding significance for the resource utilization and engineering practices.

Removal of Elemental Mercury from Flue Gas Using Cobalt-Containing Biomaterial Carbon Prepared from Contaminated Iris sibirica Biomass.

Iris sibirica biomass (ISBM) used for cobalt (Co) pollution remediation was prepared by one-step pyrolysis and employed to remove elemental mercury (Hg0) from flue gas. Results showed that the ISBM pyrolyzed at 700 °C (ISBM700) exhibited good Hg0 removal performance (about 86%) at 150 °C. The existence of NO and O2 facilitated the removal of Hg0, while SO2 and water vapor inhibited it. Characterization analysis (including N2 adsorption-desorption, X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectrometry) showed that ISBM700 has a relatively higher specific surface area, a quantity of lattice oxygen derived from well-dispersed amorphous-phase CoO x , and abundant oxygen functional groups. A Mars-Maessen mechanism is thought to be involved in the Hg0 removal process. The adsorbed Hg0 could be oxidized to HgO by the surface oxygen species derived from CoO x , and then, the consumed surface oxygen species can be replenished by O2. Therefore, the Co-contaminated I. sibirica biomass (CCIB) from phytoremediation could be utilized for Hg0 removal after being pyrolyzed instead of any chemical modification.

Interleukin-6 signaling regulates hematopoietic stem cell emergence.

Hematopoietic stem cells (HSCs) produce all lineages of mature blood cells for the lifetime of an organism. In vertebrates, HSCs derive from the transition of the hemogenic endothelium (HE) in the floor of the embryonic dorsal aorta. Most recently, a series of proinflammatory factors, such as tumor necrosis factor-α, interferon-γ, and Toll-like receptor 4, have been confirmed to play a key role in HSC specification. However, the full complement of necessary signaling inputs remains unknown to date. Here, we show that interleukin-6R (IL6R) via IL6 is required and sufficient for HSC generation. We found that Notch activates IL6R by regulating its expression in the HE and in HSCs. The secretion of IL6 mainly originates from HSC-independent myeloid cells, but not from HSCs and their adjacent vascular endothelial cells. In addition, blocking IL6 signaling does not affect vascular development or the production of primitive erythrocytes. Taken together, our results uncover a previously obscure relationship between IL6 signaling and HSC production and provide new insights into HSC regeneration using proinflammatory factors in vitro.