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Hematopoietic precursors (HPCs) entering into the thymus undergo a sequential process leading to the generation of a variety of T cell subsets. This developmental odyssey unfolds in distinct stages within the thymic cortex and medulla, shaping the landscape of T cell receptor (TCR) expression and guiding thymocytes through positive and negative selection. Initially, early thymic progenitors (ETPs) take residence in the thymic cortex, where thymocytes begin to express their TCR and undergo positive selection. Subsequently, thymocytes transition to the thymic medulla, where they undergo negative selection. Both murine and human thymocyte development can be broadly classified into distinct stages based on the expression of CD4 and CD8 coreceptors, resulting in categorizations as double negative (DN), double positive (DP) or single positive (SP) cells. Thymocyte migration to the appropriate thymic microenvironment at the right differentiation stage is pivotal for the development and the proper functioning of T cells, which is critical for adaptive immune responses. The journey of lymphoid progenitor cells into the T cell developmental pathway hinges on an ongoing dialogue between the differentiating cell and the signals emanating from the thymus niche. Herein, we review the contribution of the key factors mentioned above for the localization, migration and emigration of thymocytes.
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Diferenciación Celular , Movimiento Celular , Timocitos , Timo , Timocitos/inmunología , Timocitos/citología , Timocitos/metabolismo , Animales , Humanos , Timo/citología , Timo/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
With the development of society, the demand for cement-based composites is increasing day by day. Cement production significantly increases CO2 emissions. These emissions are reduced when high volumes of cement are replaced. The consideration of sustainable development has prompted people to search for new cement substitutes. The lignocellulosic biomass ash obtained from burning lignocellulosic biomass contains a large number of active oxides. If lignocellulosic biomass ash is used as a partial cement substitute, it can effectively solve the high emissions problem of cement-based composites. This review summarizes the physicochemical properties of lignocellulosic biomass ashes and discusses their effects on the workability, mechanical properties, and durability (water absorption, acid resistance, etc.) of cement-based composites. It is found that appropriate treatments on lignocellulosic biomass ashes are beneficial to their application in cement-based composites. Meanwhile, the issues with their application are also pointed out.
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IFN-γ is a pleiotropic cytokine that plays a controversial role in regulatory T cell (Treg) activity. In this study, we sought to understand how IFN-γ receptor (IFN-γR) signaling affects donor Tregs following allogeneic hematopoietic cell transplant (allo-HCT), a potentially curative therapy for leukemia. We show that IFN-γR signaling inhibits Treg expansion and conversion of conventional T cells (Tcons) to peripheral Tregs in both mice and humans. Mice receiving IFN-γR-deficient allo-HCT showed markedly reduced graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects, a trend associated with increased frequencies of Tregs, compared with recipients of wild-type allo-HCT. In mice receiving Treg-depleted allo-HCT, IFN-γR deficiency-induced peripheral Treg conversion was effective in preventing persistent GVHD while minimally affecting GVL effects. Thus, impairing IFN-γR signaling in Tcons may offer a promising strategy for achieving GVL effects without refractory GVHD. Similarly, in a human PBMC-induced xenogeneic GVHD model, significant inhibition of GVHD and an increase in donor Tregs were observed in mice cotransferred with human CD4 T cells that were deleted of IFN-γR1 by CRISPR/Cas9 technology, providing proof-of-concept support for using IFN-γR-deficient T cells in clinical allo-HCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia , Ratones , Humanos , Animales , Linfocitos T Reguladores , Trasplante Homólogo , Leucocitos Mononucleares , Ratones NoqueadosRESUMEN
The environmental status of seldom monitored trace elements (SMTEs) has rarely been reported in the North Yellow Sea (NYS). This study investigated the levels, sources and ecological risks of 18 SMTEs in a 209-cm-long sediment core from NYS. The concentrations of SMTEs exhibited a gradual increasing trend in the upper 70 cm. Based on the assessment results of enrichment factor (EF), geo-accumulation index (Igeo) and contamination factor (CF), obvious enrichment of Cs, Li, and U was observed for the NYS sediments, indicating possible anthropogenic sources, which are consistent with the geochemical background normalized patterns. Moreover, the pollution load index (PLI) values ranged from 0.93 to 1.24 and showed a steadily increasing trend in the upper 70 cm part, indicating gradual deterioration of environment in NYS. Combined with the multivariate statistical analysis results and PLI variations, the first principal component (PC1) with high positive loading on Be, Cs, Ga, Hf, In, Li, Nb, Rb, Sc, Ta and Tl was very likely an "anthropogenic factor". Therefore, the historical anthropogenic impact record in the NYS was reconstructed based on the PC1 scores, which indicated significant anthropogenic influence over the past 300 years. This study provides valuable information for understanding the pollution history of SMTEs and historical record of anthropogenic impact in the NYS.
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Metales Pesados , Oligoelementos , Contaminantes Químicos del Agua , Metales Pesados/análisis , Oligoelementos/análisis , Contaminantes Químicos del Agua/análisis , Efectos Antropogénicos , Sedimentos Geológicos/análisis , Monitoreo del Ambiente/métodos , China , Medición de RiesgoRESUMEN
The rapid warming of Arctic is causing increased fire activities in the boreal Northern Hemisphere (NH), leading to unprecedent changes in the global carbon cycling, human health and ecosystems. Understanding the interaction between fire and climate in this far north region is crucial for predicting future changes of wildfires. However, fire records over geological time scales are still scarce in the high latitudes of NH to provide comprehensive pictures of the fire history in this region. Here, we used the flux of levoglucosan (Lev) and its isomers in a sediment profile YN from Svalbard, high Arctic, as proxies for the changes in biomass burning from â¼9-2 kyr BP (thousand years before present). Backward trajectories and comparison with charcoal syntheses from various regions confirmed that the Lev transport to the profile site is sourced from the fire activities in the boreal NH, especially in northern Europe and northern Siberia. The Lev flux exhibited a slight overall decreasing trend at â¼3 %/kyr (p = 0.09) over the study period, as well as centennial maxima at â¼9, 8-7, 6, 5, and 4-3 kyr BP (p = 0.06). On sub-orbital scales, the long-term decrease in fire activities corresponded to trends of summer temperature in the extratropics of the NH (p = 0.01, r = 0.42), reflecting their regulation of fuel availability and flammability. On centennial to sub-millennial time scales, high levels of biomass burning were associated with periods of increased North Atlantic ice-rafted debris (p = 0.02, r = 0.38), which were indicative of cold and dry conditions over most of the source regions, reflecting the impacts of dryness on fuel flammability. The results suggested that enhanced Arctic amplification on centennial time scales may reduce biomass burning in most of the boreal NH, although fires in some mid-latitude regions may be facilitated.
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Aim: To investigate the potential of human growth hormone (hGH) to improve human hematopoietic reconstitution in humanized mice. Materials & methods: Immunodeficient mice were conditioned by total body irradiation and transplanted with human CD34+ fetal liver cells. Peripheral blood, spleen and bone marrow were harvested, and levels of human lymphohematopoietic cells were determined by flow cytometry. Results: Supplementation with hGH elevated human lymphohematopoietic chimerism by more than twofold. Treatment with hGH resulted in significantly increased reconstitution of human B cells and myeloid cells in lymphoid organs, enhanced human erythropoiesis in the bone morrow, and improved engraftment of human hematopoietic stem cells. Conclusion: hGH supplementation promotes human lymphohematopoietic reconstitution in humanized mice.
Humanized mice generated by human hematopoietic stem cell transplantation play crucial roles in biomedical investigations. One of the factors hindering the efficacy of their construction is the lack of or insufficient interaction of human cells to mouse cytokines and growth hormones (GHs) that are crucial for hematopoiesis and immune cell differentiation. In this study, we show that injection of human GH significantly improved human hematopoietic stem cell engraftment and function, as well as immune cell reconstitution in humanized mice. Our findings indicate that human cells may not efficiently respond to mouse GH, and generation of immunodeficient mice producing human GH may improve the efficacy of humanized mouse construction.
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Trasplante de Células Madre Hematopoyéticas , Hormona de Crecimiento Humana , Reconstitución Inmune , Animales , Humanos , Ratones , Suplementos Dietéticos , Células Madre Hematopoyéticas , Hormona de Crecimiento Humana/farmacología , Ratones SCIDRESUMEN
Nanoparticles have been investigated as drug carriers and promising agents for cancer therapy. However, the tumor microenvironment (TME), which is formed by the tumor, is considered a barrier for nanocarriers to enter the internal tumor tissue. Therefore, the evaluation of the biological distribution of nanocarriers in TME can provide useful information on their role in tumor-targeted drug delivery. Although the tumor-bearing mouse model is commonly used to investigate the distribution of nanocarriers in the TME, there is currently a lack of a testing system to predict the distribution of nanocarriers in tumor tissues, especially in patients. This study revealed that the macrophages and dendritic cells (DCs) were more distributed in the peripheral part than the central part of the tumor, which might be an obstacle to the uniform distribution of nanoparticles in the tumor. In addition, the cellular uptake of gold nanoparticles (AuNR and AuNS) in macrophages and DCs cell lines (RAW264.7 and DC1.2) was markedly different from that in the TME. Hence, the study model of the interaction between nanoparticles and macrophages and DCs has an important impact on the accuracy of the results. The vibratome sections of tumor tissues preserved the spatial distribution of immune cells and tumor cells, and had very little effects on their morphologies and activities. More importantly, we found that the distribution of nanocarriers in vibratome sections was similar to that in tumors in vivo. In all, ex vivo analysis using vibratome sections of tumor tissues provides a more convenient and stable method for elucidating the influences of TME on the distribution of nanocarriers.
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The marine environment of coastal Shandong Peninsula has been significantly influenced by anthropogenic activities due to the rapid industrialization and economic development in the past decades. However, the sedimentary records of PTEs in the North Yellow Sea have rarely been reported. In this study, a 209-cm-long sediment core was collected off the northern coast of Shandong Peninsula, analyzed for grain size and elemental compositions, and assessed using EF, Igeo and several numerical Sediment Quality Guidelines (SQGs). The EF and Igeo results suggested that sediment profile could be slightly to moderately polluted with As and Sb, while ecological risk assessment using SQGs showed that As, Cr, Sb and Ni in the sediment profile may have a moderate incidence of toxicity. Our results highlighted the nonnegligible ecological risk of Sb in sediments of North Yellow Sea, and great importance should be attached to the fact that many PTEs may also pose a potential ecological risk to the aquatic organisms, even though their concentrations meet the standards of the Marine Sediments Quality (MSQ). Moreover, the reconstructed PTEs record showed a dramatic increase over the past 250 years, which could be related to the intense anthropogenic activities since the Industrial Revolution. The multivariate statistical analysis results indicated that Co, Cr, Cu, Pb, Ni and Zn may be mainly related to the natural origin, while As and Sb could be influenced by both natural weathering sources and anthropogenic activities. This study provides more insights into the historical record of PTEs in the North Yellow Sea, and lays foundation for future comparison of PTEs sedimentary records.
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Metales Pesados , Contaminantes Químicos del Agua , Calibración , China , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/análisis , Plomo/análisis , Metales Pesados/análisis , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Ischemic stroke (IS) is a leading cause of death and disability worldwide. Currently, the main therapeutic strategy involves the use of intravenous thrombolysis to restore cerebral blood flow to prevent the transition of the penumbra to the infarct core. However, due to various limitations and complications, including the narrow time window in which this approach is effective, less than 10% of patients benefit from such therapy. Thus, there is an urgent need for alternative therapeutic strategies, with neuroprotection against the ischemic cascade response after IS being one of the most promising options. In the past few decades, polyphenolic compounds have shown great potential in animal models of IS because of their high biocompatibility and ability to target multiple ischemic cascade signaling pathways, although low bioavailability is an issue that limits the applications of several polyphenols. Here, we review the pathophysiological changes following cerebral ischemia and summarize the research progress regarding the applications of polyphenolic compounds in the treatment of IS over the past 5 years. Furthermore, we discuss several potential strategies for improving the bioavailability of polyphenolic compounds as well as some essential issues that remain to be addressed for the translation of the related therapies to the clinic.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Isquemia Encefálica/tratamiento farmacológico , Circulación Cerebrovascular , Polifenoles/farmacología , Polifenoles/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Thymic epithelial cells (TECs) are essential for the production of self-tolerant T cells. The newly identified thymic tuft cells are regulated by Pou2f3 and represent important elements for host type 2 immunity. However, epigenetic involvement in thymic tuft cell development remains unclear. We performed single-cell ATAC-seq of medullary TEC (mTEC) and established single-cell chromatin accessibility profiling of mTECs. The results showed that mTEC III cells can be further divided into three groups (Late Aire 1, 2, and 3) and that thymic tuft cells may be derived from Late Aire 2 cells. Pou2f3 is expressed in both Late Aire 2 cells and thymic tuft cells, while Pou2f3-regulated genes are specifically expressed in thymic tuft cells with simultaneous opening of chromatin accessibility, indicating the involvement of epigenetic modification in this process. Using the epigenetic regulator Sirt6-defect mouse model, we found that Sirt6 deletion increased Late Aire 2 cells and decreased thymic tuft cells and Late Aire 3 cells without affecting Pou2f3 expression. However, Sirt6 deletion reduced the chromatin accessibility of Pou2f3-regulated genes in thymic tuft cells, which may be caused by Sirt6-mediated regulation of Hdac9 expression. These data indicate that epigenetic regulation is indispensable for Pou2f3-mediated thymic tuft cell development.
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Epigénesis Genética , Sirtuinas , Animales , Diferenciación Celular/genética , Cromatina/genética , Cromatina/metabolismo , ADN/metabolismo , Células Epiteliales/metabolismo , Ratones , Sirtuinas/genética , Sirtuinas/metabolismoRESUMEN
BACKGROUND: Graft-versus-host disease (GVHD) is a common fatal complication of hematopoietic stem cell transplantation (HSCT), where steroids are used as a treatment option. However, there are currently no second-line treatments for patients that develop steroid-resistance (SR). Mesenchymal stem cells (MSCs) have immunomodulatory functions and can exert immunosuppressive effects on the inflammatory microenvironment. A large number of in vitro experiments have confirmed that MSCs can significantly inhibit the proliferation or activation of innate and adaptive immune cells. In a mouse model of GVHD, MSCs improved weight loss and increased survival rate. Therefore, there is great promise for the clinical translation of MSCs for the prevention or treatment of GVHD, and several clinical trials have already been conducted to date. MAIN BODY: In this study, we searched multiple databases and found 79 clinical trials involving the use of MSCs to prevent or treat GVHD and summarized the characteristics of these clinical trials, including study design, phase, status, and locations. We analyzed the results of these clinical trials, including the response and survival rates, to enable researchers to obtain a comprehensive understanding of the field's progress, challenges, limitations, and future development trends. Additionally, factors that might result in inconsistencies in clinical trial results were discussed. CONCLUSION: In this study, we attempted to analyze the clinical trials for MSCs in GVHD, identify the most suitable group of patients for MSC therapy, and provide a new perspective for the design of such trials in the future.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Tolerancia Inmunológica , Trasplante de Células Madre Mesenquimatosas/métodos , RatonesRESUMEN
Thymic epithelial cells (TECs) are critical for the development and generation of functionally competent T cells. Until now, the mechanism that regulates the survival of TECs is poorly understood. In the current study, we found that Tsc1 controls the homeostasis of medullary TECs (mTECs) by inhibiting lysosomal-mediated apoptosis pathway in mice. TEC-specific deletion of Tsc1 predominately decreased the cell number of mTECs and, to a lesser content, affected the development cortical TECs. The defect of mTECs caused by Tsc1 deficiency in mice impaired thymocyte development and peripheral T cell homeostasis. Mechanistically, Tsc1 deficiency did not affect the cell proliferation of mTECs but increased the apoptosis of mTECs significantly. RNA-sequencing analysis showed that pathways involved in lysosomal biogenesis, cell metabolism, and apoptosis were remarkably elevated in Tsc1-deficient mTECs compared with their wild-type counterparts. Tsc1-deficient mTECs exhibited overproduction of reactive oxygen species and malfunction of lysosome, with lysosome membrane permeabilization and the release of cathepsin B and cathepsin L to the cytosol, which then lead to Bid cleaved into active truncated Bid and subsequently intrinsic apoptosis. Finally, we showed that the impaired development of mTECs could be partially reversed by decreasing mTORC1 activity via haploinsufficiency of Raptor Thus, Tsc1 is essential for the homeostasis of mTECs by inhibiting lysosomal-mediated apoptosis through mTORC1-dependent pathways.
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Células Epiteliales/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Timo/citología , Proteína 1 del Complejo de la Esclerosis Tuberosa/metabolismo , Animales , Apoptosis , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Células Epiteliales/citología , Retroalimentación Fisiológica , Haploinsuficiencia , Homeostasis , Ratones , Ratones Noqueados , Especies Reactivas de Oxígeno/metabolismo , Proteína Reguladora Asociada a mTOR/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/genéticaRESUMEN
Metal contamination has become an increasingly severe environmental issue due to intense anthropogenic activities in recent decades. Many studies have reported a rapidly increasing trend of heavy metal contents in sedimentary records. In this study, two lacustrine sediment cores (LDL and YL) far away from scientific research stations were collected in Ny-Ålesund and analyzed for the vertical distributions of 17 elemental concentrations (Cu, Zn, Pb, Co, Ni, Cr, Sr, Ba, Mn, P, Ti, K2O, Na2O, CaO, MgO, Fe2O3, Al2O3), CIA and TOC contents. The results indicated that only the proxies Pb, P, CaO, TOC, and CIA showed an increasing trend in the upper 7 cm section of the sediment cores, while most of the elements' concentrations decreased towards the surface. The rapid increase of TOC contents is likely related to the climate warming over the past 200 years, which promotes the prosperity of vegetation and thus leads to more input of organic matter into the lakes. Moreover, a large number of seabirds live around the sampling position and the seabird guano contains high concentrations of P, which could be regarded as an important nutrient source for vegetation. Additionally, the rapid climate warming could accelerate the chemical weathering rates, and thus lead to increased CaO contents in the sediment profiles according to its geological background. Therefore, the concentrations of other elements are very likely diluted by the high contents of organic matter and CaO in the upper part of the sediment cores. It is noteworthy that the rapidly increasing trend of Pb contents are related to the gas-oil powered generators in Ny-Ålesund and long-range atmospheric transport from Europe. This study highlighted the nonnegligible influence of climate warming on the inorganic elemental geochemistry distributions in remote lakes.
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Metales Pesados , Contaminantes Químicos del Agua , Regiones Árticas , Cambio Climático , Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados/análisis , Svalbard , Contaminantes Químicos del Agua/análisisRESUMEN
Mouse models are the most commonly used in vivo system for biomedical research, in which immune-related diseases and therapies can be investigated in syngeneic and immunologically intact hosts. However, because there are significant differences between rodent and human, most findings from conventional mouse models cannot be applied to humans. The humanized mouse with a functional human immune system, also referred to as human immune system (HIS) mouse, is the only model available to date for in vivo studies in real-time of human immune function under physiological and pathological conditions. HIS mice with human tumor xenografts are considered an emerging and promising in vivo model for modeling human cancer immunotherapy. In this review, we briefly discuss the protocols to construct HIS mice and elaborate their pros and cons. Particular attention is given to HIS mouse models with human tumor that is autologous or genetically identical to the human immune system, which are discussed with examples of their usefulness in modeling human cancer immunotherapies.
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Autoinjertos , Modelos Animales de Enfermedad , Inmunoterapia , Neoplasias/inmunología , Neoplasias/terapia , Animales , Trasplante de Médula Ósea , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Humanos , Inmunoterapia/métodos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Trasplante HeterólogoRESUMEN
Thymic involution is an important factor leading to the aging of the immune system. Most of what we know regarding thymic aging comes from mouse models, and the nature of the thymic aging process in humans remains largely unexplored due to the lack of a model system that permits longitudinal studies of human thymic involution. In this study, we sought to explore the potential to examine human thymic involution in humanized mice, constructed by transplantation of fetal human thymus and CD34+ hematopoietic stem/progenitor cells into immunodeficient mice. In these humanized mice, the human thymic graft first underwent acute recoverable involution caused presumably by transplantation stress, followed by an age-related chronic form of involution. Although both the early recoverable and later age-related thymic involution were associated with a decrease in thymic epithelial cells and recent thymic emigrants, only the latter was associated with an increase in adipose tissue mass in the thymus. Furthermore, human thymic grafts showed a dramatic reduction in FOXN1 and AIRE expression by 10 weeks post-transplantation. This study indicates that human thymus retains its intrinsic mechanisms of aging and susceptibility to stress-induced involution when transplanted into immunodeficient mice, offering a potentially useful in vivo model to study human thymic involution and to test therapeutic interventions.
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Envejecimiento/fisiología , Timo/inmunología , Timo/metabolismo , Animales , Biomarcadores , Movimiento Celular , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Humanos , Inmunofenotipificación , Ratones , Ratones Transgénicos , Modelos Animales , Reacción en Cadena en Tiempo Real de la Polimerasa , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Timo/citologíaRESUMEN
Ny-Ålesund has been significantly impacted by anthropogenic activities (e.g. coal mining, scientific research, tourist shipping) over the past 100 years. However, the studies of potential toxic elements (PTEs) contamination in Ny-Ålesund currently mainly focus on surface soil or surface fjord sediments, and little is known about the history and status of PTEs contamination over the past 100 years. In this study, we collected a palaeo-notch sediment profile YN, analyzed the contents of six typical PTEs (Cu, Pb, Cd, Hg, As, Se) in the sediments, and assessed the historical pollution status in Ny-Ålesund using the pollution load index, geo-accumulation index and enrichment factor. The results showed that the contents of PTEs over the past 100 years increased rapidly compared with those during the interval of 9400-100 BP. In addition, Pb, Cd and Hg showed a clear signal of enrichment and were the main polluters among the PTEs analyzed. The contamination was likely linked to gas-oil powered generators, coal mining, research station, tourist shipping and long-range transport of pollutants.
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Metales Pesados/análisis , Contaminantes del Suelo/análisis , Monitoreo del Ambiente , Medición de Riesgo , Suelo , SvalbardRESUMEN
The El Niño-Southern Oscillation (ENSO) is the principal climatic system in the modern Pacific Ocean, and it potentially influences the global climate. The South China Sea (SCS), in the western tropical Pacific, is significantly affected by ENSO activity. We have conducted a high-resolution oxygen isotope study of the shells of one modern and four fossil Tridacna from the Xisha Islands in the SCS. The results for the modern sample reveal that the shells of Tridacna are a good proxy of ENSO variability. We used the results of the oxygen isotope composition of four fossil Tridacna to produce high-resolution records of ENSO activity during four time slices in the Holocene. The results indicate that ENSO variability in the early Holocene was comparable to that of today, and that a minimum in the frequency and intensity of ENSO activity occurred in the mid Holocene. These findings are consistent with paleoclimatic results from corals, mollusks and sedimentary records. However, the observed extremely low frequency and moderate ENSO intensity at 4.7 ka indicate an anomalous pattern of ENSO changes within this interval of climatic transition. In addition, seasonal temperature variations during the Holocene were different from those of today and extreme seasonality may also occur during warmer periods.
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CD47 (cluster of differentiation 47) is a ubiquitously expressed transmembrane protein that belongs to the immunoglobulin superfamily. CD47 is both a receptor for the matricellular protein thrombospondin-1 (TSP-1) and a ligand for signal-regulatory protein alpha (SIRPα). Suppression of CD47 activity enhances angiogenesis and blood flow, restores phagocytosis by macrophages, improves ischemic tissue survival, attenuates ischemia reperfusion injury, and reverses atherosclerotic plaque formation. In conclusion, these observations suggest a pathogenic role of CD47 in the development of cardiovascular diseases (CVDs) and indicate that CD47 might be a potentially promising molecular target for treating CVDs. Herein, we highlight the role of CD47 in the CVD pathogenesis and discuss the potential clinical application by targeting CD47 for treating CVDs.
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Antígeno CD47/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Terapia Molecular Dirigida , Animales , Antígenos de Diferenciación/metabolismo , Biomarcadores/metabolismo , Antígeno CD47/antagonistas & inhibidores , Antígeno CD47/genética , Enfermedades Cardiovasculares/metabolismo , Humanos , Isquemia/metabolismo , Macrófagos/metabolismo , Neovascularización Patológica/metabolismo , Receptores Inmunológicos/metabolismo , Linfocitos T/metabolismo , Trombospondina 1/metabolismoRESUMEN
Heavy metal contaminants in Mirror Peninsula, East Antarctica, have rarely been studied and the source and influencing factors are poorly understood. We sampled a grid of 189 topsoil samples from Mirror Peninsula and analyzed the concentrations of Zn, Cu, U, Cr, Ga, Pb, Hg, Se and As; we also calculated the chemical index of alteration (CIA), a proxy of weathering. The results show that the distributions of Cr, Ga, Cu, and Zn are associated with weathering; the distributions of As and Pb are related to vehicle use and unloading activities at the wharfs, respectively; and the distribution of Hg is likely associated with both anthropogenic impacts and biological activity. The contamination level of these heavy metals in Mirror Peninsula is relatively low and within the controllable range. Both weathering processes and anthropogenic impacts can cause the enrichment of heavy metals; thus reliable source apportionment is crucial in studying heavy metal enrichment and contamination.
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Monitoreo del Ambiente , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Regiones Antárticas , China , MercurioRESUMEN
BACKGROUND: Graft-versus-host disease (GVHD) is one of the most complex complications after allogeneic stem cell transplantation. Current standard of grading system is based on clinical symptoms in skin, liver and intestinal. However, it's difficult to differ GVHD and its extent just by clinical manifestation. Here we retrospectively analyzed cell immune function in patients implemented allogeneic stem cell transplantation in Ningbo first Hospital from Jan 2013 to Jan 2018. RESULTS: the data are collected from 51 patients (mean age was 42; 45.1% women). The average NK cell percentage was 39.31% in severe GVHD (Grade III-IV), was 16.98% in mild GVHD (GradeI-II), while was 21.15% in No GVHD group. The statistical analysis showed difference among each grade. Further analysis was performed in Antithymocyte globulin (ATG) treated group and control group. We showed NK Cell percentage was sharply different in ATG treated group: 47.34% in severe GVHD, 11.98% in mild GVHD group, while 18.3% in no GVHD group. However, in control group, the average percentage of NK cells was 23.27% in severe GVHD, was 23.22%in mild GVHD group, while was 21.13% in no GVHD group. CONCLUSION: The data supports that ATG can prevent GVHD by increasing NK cell percentage. The percentage of NK cell seemed to be a useful probe to evaluate the severity of GVHD in allogeneic stem cell transplantation patients using ATG in pretreatment.