31 research outputs found

    TREM2-dependent effects on microglia in Alzheimer\u27s Disease

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    Alzheimer’s disease (AD) is a late-onset dementia characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain are also associated with reactive microglia and astrocytes. Whether this glial response is beneficial or detrimental in AD pathology is under debate. Microglia are the resident innate immune cells in the central nervous system (CNS) that survey the surrounding environment. Genome-wide association studies (GWAS) have identified the R47H variant of triggering receptor expressed on myeloid cell 2 (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds to polyanionic molecules. The transmembrane domain of TREM2 signals through DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based activation motif (ITAM), which mediates TREM2 signaling and promotes microglial activation and survival. In mouse models of AD, Trem2 haplodeficiency and deficiency lead to reduced microglial clustering around amyloid β (Aβ) plaques, suggesting TREM2 is required for plaque-associated microglial responses. Recently, TREM2 has been shown to enhance microglial metabolism through the mammalian target of rapamycin (mTOR) pathway. Although aberrant metabolism has long been associated with AD, not much was known regarding how metabolism in microglia might affect disease progression. In this review, we discuss the role of TREM2 and metabolism in AD pathology, highlighting how TREM2-mediated microglial metabolism modulates AD pathogenesis

    TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis

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    Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials

    Progress in Application of CNTs in Lithium-Ion Batteries

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    The lithium-ion battery is widely used in the fields of portable devices and electric cars with its superior performance and promising energy storage applications. The unique one-dimensional structure formed by the graphene layer makes carbon nanotubes possess excellent mechanical, electrical, and electrochemical properties and becomes a hot material in the research of lithium-ion battery. In this paper, the applicable research progress of carbon nanotubes in lithium-ion battery is described, and its future development is put forward from its two aspects of being not only the anodic conductive reinforcing material and the cathodic energy storage material but also the electrically conductive framework material

    Macerals of lignite and the effect of alkali treatment on the structure and combustion performance of lignite

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    Suppressing the spontaneous combustion of lignite is of great significance for safe transportation and efficient utilization of lignite. Taking the Shengli lignite as the research object, two different macerals, inertinite and huminite, were selected by optical microscope, and treated with NaOH respectively to study the relationship between the structure and combustion reaction performance of different macerals and lignite treated with NaOH. The structure of the prepared coal samples was characterized by SEM-EDS, XPS, FT-IR, XRD and Raman, and the changes of the main functional groups were analyzed. The effect of NaOH treatment on the combustion performance of different maceral lignite was investigated by TGA. The results showed that the ignition temperature of huminite lignite was about 10 ℃ earlier than that of inertinite, but the comprehensive combustion characteristic index of inertinite lignite was slightly higher than that of huminite. After the NaOH treatment, the lignite of different macerals showed a hysteresis of combustion, there were two obvious weight losses in the range of 200−500 ℃ and 650−800 ℃, respectively, and the mass loss was mainly concentrated in the second weight loss, in particular, the effect of huminite lignite was more significant, and the temperature corresponding to the maximum combustion reaction rate was about 60 ℃ behind that of inertinite. The kinetic analysis of the combustion process of the coal samples showed that the activation energy of combustion reaction of lignite with different macerals significantly increased after the NaOH treatment, and the huminite lignite was higher than that of inertinite lignite. The XPS/FT-IR results revealed that the contents of carboxylic oxygen-containing functional groups in different macerals of lignite treated by NaOH decreased, the main reason is that in the process of NaOH treatment, Na+ interacted with the carboxylic oxygen-containing functional groups in lignite to form the sodium carboxylate structure, and the relative amount of the sodium carboxylate structure in huminite coal was relatively large. It is believed that the inhibitory effect on the combustion of lignite with different macerals is attributed to the stability of the sodium carboxylate structure, and the number of the sodium carboxylate structure formed by combining with Na is the main reason for the difference in its combustion performance. The XRD/Raman analysis indicates that the formation of the sodium carboxylate structure in lignite leads to the increase of the order degree of carbon microcrystalline structure, and the order degree of huminite lignite is higher than that in inertinite

    Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination

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    Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAF

    The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends

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    BackgroundThe incidence of non-Hodgkin’s lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally.MethodsThe up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040.ResultsIn 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040.ConclusionIn this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries

    TREM2-Dependent Effects on Microglia in Alzheimer’s Disease

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    Alzheimer’s disease (AD) is a late-onset dementia characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain are also associated with reactive microglia and astrocytes. Whether this glial response is beneficial or detrimental in AD pathology is under debate. Microglia are the resident innate immune cells in the central nervous system (CNS) that survey the surrounding environment. Genome-wide association studies (GWAS) have identified the R47H variant of triggering receptor expressed on myeloid cell 2 (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds to polyanionic molecules. The transmembrane domain of TREM2 signals through DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based activation motif (ITAM), which mediates TREM2 signaling and promotes microglial activation and survival. In mouse models of AD, Trem2 haplodeficiency and deficiency lead to reduced microglial clustering around amyloid β (Aβ) plaques, suggesting TREM2 is required for plaque-associated microglial responses. Recently, TREM2 has been shown to enhance microglial metabolism through the mammalian target of rapamycin (mTOR) pathway. Although aberrant metabolism has long been associated with AD, not much was known regarding how metabolism in microglia might affect disease progression. In this review, we discuss the role of TREM2 and metabolism in AD pathology, highlighting how TREM2-mediated microglial metabolism modulates AD pathogenesis

    Genome-Wide Organization and Expression Profiling of the SBP-Box Gene Family in Chinese Jujube (Ziziphus jujuba Mill.)

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    Transcription factors play vital roles in the developmental processes of plants. The SQUAMOSA promoter binding protein (SBP) genes encode a family of plant-specific transcription factors and plays many crucial roles in plant development. In this study, 16 SBP-box gene family members were identified in Ziziphus jujuba Mill. Dongzao (Dongzao), which were distributed over 8 chromosomes. They were classified into seven groups according to their phylogenetic relationships with other SBP-box gene families. Within each group, genes shared similar exon-intron structures and motif locations. The number of exons varied among the groups. We identified 12 homologous gene pairs between Dongzao and Arabidopsis. Expression profiling revealed that ZjSBP02 and ZjSBP14 expressed highly in mature fruits, ZjSBP01 expressed higher in mature leaves than other tissues and the expression level of ZjSBP12 was much higher in the flowers. The transcriptome analysis indicated that ZjSBPs had different expression patterns in various tissues. This study represents the first systematic analysis of the SBP-box gene family in Z. jujuba. The data presented here provides a foundation for understanding the crucial roles of ZjSBP genes in plant growth and development
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