A unique feature of the pathological change after spinal cord injury (SCI) is the progressive enlargement of lesion area, which usually results in cavity formation and is accompanied by reactive ...astrogliosis and chronic inflammation. Reactive astrocytes line the spinal cavity, walling off the lesion core from the normal spinal tissue, and are thought to play multiple important roles in SCI. The contribution of cell death, particularly the apoptosis of neurons and oligodendrocytes during the process of cavitation has been extensively studied. However, how reactive astrocytes are eliminated following SCI remains largely unclear.
By immunohistochemistry, in vivo propidium iodide (PI)-labeling and electron microscopic examination, here we reported that in mice, reactive astrocytes died by receptor-interacting protein 3 and mixed lineage kinase domain-like protein (RIP3/MLKL) mediated necroptosis, rather than apoptosis or autophagy. Inhibiting receptor-interacting protein 1 (RIP1) or depleting RIP3 not only significantly attenuated astrocyte death but also rescued the neurotrophic function of astrocytes. The astrocytic expression of necroptotic markers followed the polarization of M1 microglia/macrophages after SCI. Depleting M1 microglia/macrophages or transplantation of M1 macrophages could significantly reduce or increase the necroptosis of astrocytes. Further, the inflammatory responsive genes Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) are induced in necroptotic astrocytes. In vitro antagonizing MyD88 in astrocytes could significantly alleviate the M1 microglia/macrophages-induced cell death. Finally, our data showed that in human, necroptotic markers and TLR4/MyD88 were co-expressed in astrocytes of injured, but not normal spinal cord.
Taken together, these results reveal that after SCI, reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis, partially through TLR/MyD88 signaling, and suggest that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Identification of quantitative trait loci (QTL) for fiber quality traits that are stable across multiple generations and environments could facilitate marker-assisted selection for improving cotton ...strains. In the present study, F
2
, F
2:3
, and recombinant inbred lines (RILs, F
6:8
) populations derived from an upland cotton (
Gossypium hirsutum
L.) cross between strain 0-153, which has excellent fiber quality, and strain sGK9708, a commercial transgenic cultivar, were constructed for QTL tagging of fiber quality. We used 5,742 simple sequence repeat primer pairs to screen for polymorphisms between the two parent strains. Linkage maps of F
2
and RILs were constructed, containing 155 and 190 loci and with a total map distance of 959.4 centimorgans (cM) and 700.9 cM, respectively. We screened fiber quality QTL across multiple generations and environments through composite interval mapping of fiber quality data. Specifically, we studied F
2
and F
2:3
family lines from Anyang (Henan Province) in 2003 and 2004 and RILs in Anyang in 2007 and Anyang, Quzhou (Hebei Province), and Linqing (Shandong Province) in 2008. We identified 50 QTL for fiber quality: 10 for fiber strength, 10 for fiber length, 10 for micronaire, eight for fiber uniformity, and 12 for fiber elongation. Nine of these fiber quality QTL were identified in F
2
, F
2:3
and RILs simultaneously. Two QTL for fiber strength on chromosomes C7 and C25 were detected in all three generations and all four environments and explained 16.67–27.86% and 9.43–21.36% of the phenotypic variation, respectively. These stable QTL for fiber quality traits could be used for marker assisted selection.
Recently, an increasing number of studies have revealed that N6-methyladenosine (m6A) functions as a significant post-transcriptional modification which plays a critical role in the occurrence and ...progression of enriched tumors by regulating coding and non-coding RNA biogenesis. However, the biological function of m6A in breast cancer remains largely unclear.
In this study, we used a series of bioinformatic databases and tools to jointly analyze the expression of m6A methylation transferases (METTL3, METTL14, WTAP, RBM15, RBM15B and ZC3H13) and investigate the prognostic value of METTL14 and ZC3H13 in breast cancer. Besides, we analyzed the downstream carcinogenic molecular mechanisms related to METTL14 and ZC3H13 and their relationship with immune infiltration in breast tumor tissues.
The results showed that METTL14 and ZC3H13 were the down-regulated m6A methylation transferases in breast cancer. Survival outcome analysis suggested that abnormally low expression of METTL14 and ZC3H13 could predict unfavorable prognosis in four breast cancer subtypes. Moreover, their down-regulation was associated with ER-, PR- and triple-negative breast cancer patients, as well as tumor progression (increased Scarff, Bloom and Richardson grade status and Nottingham Prognostic Index classification). Co-expression analysis revealed that METTL14 and ZC3H13 had a strong positive correlation with APC, an antagonist of the Wnt signaling pathway, indicating they might cooperate in regulating proliferation, invasion, and metastasis of tumor cells. METTL14, ZC3H13, and APC expression levels had significant positive correlation with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, and negative correlation with Treg cells in breast cancer.
This study demonstrated that down-regulation of METTL14 and ZC3H13 which act as two tumor suppressor genes was found in breast cancer and predicted poor prognosis. Their abnormal expression promoted breast cancer invasion by affecting pathways related to tumor progression and mediating immunosuppression.
How to develop new cotton varieties possessing high yield traits of Upland cotton and superior fiber quality traits of Sea Island cotton remains a key task for cotton breeders and researchers. While ...multiple attempts bring in little significant progresses, the development of Chromosome Segment Substitution Lines (CSSLs) from Gossypium barbadense in G. hirsutum background provided ideal materials for aforementioned breeding purposes in upland cotton improvement. Based on the excellent fiber performance and relatively clear chromosome substitution segments information identified by Simple Sequence Repeat (SSR) markers, two CSSLs, MBI9915 and MBI9749, together with the recurrent parent CCRI36 were chosen to conduct transcriptome sequencing during the development stages of fiber elongation and Secondary Cell Wall (SCW) synthesis (from 10DPA and 28DPA), aiming at revealing the mechanism of fiber development and the potential contribution of chromosome substitution segments from Sea Island cotton to fiber development of Upland cotton.
In total, 15 RNA-seq libraries were constructed and sequenced separately, generating 705.433 million clean reads with mean GC content of 45.13% and average Q30 of 90.26%. Through multiple comparisons between libraries, 1801 differentially expressed genes (DEGs) were identified, of which the 902 up-regulated DEGs were mainly involved in cell wall organization and response to oxidative stress and auxin, while the 898 down-regulated ones participated in translation, regulation of transcription, DNA-templated and cytoplasmic translation based on GO annotation and KEGG enrichment analysis. Subsequently, STEM software was performed to explicate the temporal expression pattern of DEGs. Two peroxidases and four flavonoid pathway-related genes were identified in the "oxidation-reduction process", which could play a role in fiber development and quality formation. Finally, the reliability of RNA-seq data was validated by quantitative real-time PCR of randomly selected 20 genes.
The present report focuses on the similarities and differences of transcriptome profiles between the two CSSLs and the recurrent parent CCRI36 and provides novel insights into the molecular mechanism of fiber development, and into further exploration of the feasible contribution of G. barbadense substitution segments to fiber quality formation, which will lay solid foundation for simultaneously improving fiber yield and quality of upland cotton through CSSLs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, a facile yet efficient interfacial hydrothermal process was successfully developed to fabricate LiMnPO4/C composites. In this strategy, the walls of carbon nanotubes were employed as ...heterogeneous nucleation interfaces and biomass of phytic acid (PA) as an eco-friendly phosphorus source. By comparing the experimental results, a reasonable nucleation-growth mechanism was proposed, suggesting the advantages of interfacial effects. Meanwhile, the as-synthesized LiMnPO4/C samples exhibited superior rate performances with discharge capacities reaching 161 mA h g−1 at C/20, 134 mA h g−1 at 1C, and 100 mA h g−1 at 5C. The composites also displayed excellent cycling stabilities by maintaining 95% of the initial capacity over 100 continuous cycles at 1C. Electrochemical impedance spectroscopy showed that the superior electrochemical performances were attributed to the low charge-transfer resistance and elevated diffusion coefficient of lithium ions. In sum, the proposed approach for the preparation of LiMnPO4/C composites looks promising for future production of composite electrode materials for high-performance lithium-ion batteries.
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IJS, KILJ, NUK, UL, UM, UPUK
Verticillium wilt (VW), also known as "cotton cancer," is one of the most destructive diseases in global cotton production that seriously impacts fiber yield and quality. Despite numerous attempts, ...little significant progress has been made in improving the VW resistance of upland cotton. The development of chromosome segment substitution lines (CSSLs) from Gossypium hirsutum × G. barbadense has emerged as a means of simultaneously developing new cotton varieties with high-yield, superior fiber, and resistance to VW.
In this study, VW-resistant investigations were first conducted in an artificial greenhouse, a natural field, and diseased nursery conditions, resulting in the identification of one stably VW-resistant CSSL, MBI8255, and one VW-susceptible G. hirsutum, CCRI36, which were subsequently subjected to biochemical tests and transcriptome sequencing during V991 infection (0, 1, and 2 days after inoculation). Eighteen root samples with three replications were collected to perform multiple comparisons of enzyme activity and biochemical substance contents. The findings indicated that VW resistance was positively correlated with peroxidase and polyphenol oxidase activity, but negatively correlated with malondialdehyde content. Additionally, RNA sequencing was used for the same root samples, resulting in a total of 77,412 genes, of which 23,180 differentially expressed genes were identified from multiple comparisons between samples. After Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on the expression profiles identified using Short Time-series Expression Miner, we found that the metabolic process in the biological process, as well as the pathways of phenylpropanoid biosynthesis and plant hormone signal transduction, participated significantly in the response to VW. Gene functional annotation and expression quantity analysis indicated the important roles of the phenylpropanoid metabolic pathway and oxidation-reduction process in response to VW, which also provided plenty of candidate genes related to plant resistance.
This study concentrates on the preliminary response to V991 infection by comparing the VW-resistant CSSL and its VW-susceptible recurrent parent. Not only do our findings facilitate the culturing of new resistant varieties with high yield and superior performance, but they also broaden our understanding of the mechanisms of cotton resistance to VW.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The airway epithelium is thought to play an important role in the pathogenesis of asthma. Airway epithelial activation may contribute to inflammatory and airway-remodeling events characteristic of ...asthma. Kaempferol, a flavonoid with antioxidative and antitumor properties, has been studied as an antiinflammatory agent. However, little is known regarding its effects on allergic asthma. Human airway epithelial BEAS-2B cells and eosinophils were used to investigate the effects of kaempferol on endotoxin- or cytokine-associated airway inflammation. Kaempferol, nontoxic at 1-20 μmol/L, suppressed LPS-induced eotaxin-1 protein expression that may be mediated, likely via Janus kinase 2 (JAK2) JAK2 signaling. Additionally, 1-20 μmol/L kaempferol dose-dependently attenuated TNFα-induced expression of epithelial intracellular cell adhesion molecule-1 and eosinophil integrin β2, thus encumbering the eosinophil-airway epithelium interaction. Kaempferol blunted TNFα-induced airway inflammation by attenuating monocyte chemoattractant protein-1 transcription, possibly by disturbing NF-κB signaling. This study further investigated antiallergic activity of kaempferol in BALB/c mice sensitized with ovalbumin (OVA) and challenged with a single dose of OVA. Oral administration of kaempferol attenuated OVA challenge-elevated expression of eotaxin-1 and eosinophil major basic protein via the blockade of NF-κB transactivation, thereby blunting eosinophil accumulation in airway and lung tissue. Therefore, dietary kaempferol is effective in ameliorating allergic and inflammatory airway diseases through disturbing NF-κB signaling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cotton is a widely grown crop to produce natural textile fiber, and improving the fiber strength (FS) is one of the main targets that cotton breeders focus on. The long-term natural selection and ...domestication have produced abundant germplasm resources of Gossypium hirsutum, and exploring genetic underpinnings underlying these FS innovation in elite collections is crucial. PCAMP is proposed as a most optimized NGS based bulked segregant analysis (NGS-BSA) for the high-resolution identification of markers linked to specific genomic regions through pairwise comparing multiple BSA bulks. In this study, we firstly applied PCAMP to resolved the FS genetic architecture in G. hirsutum cv. CCRI127. As an extension for PCAMP approach, graded bulks were constructed using F2 segregants with the FS phenotype revalidated by F2:3 lines, and then, a major QTL was eventually narrowed to 2.47 Mb from 8.14 Mb generated by traditional BSA approaches. Subsequently, through a saturated genetic map constructed in this locus, an novel FS gene, GhCKX1, predicted to produce a cytokinin (CTK) oxidase was isolated. It can negatively modulate the CTK signaling circuit via irreversible degradation of CTKs, resulting in an additional cell wall thickness to xylem tracheary elements in transgenic lines of Arabidopsis thaliana. Thus, the GhCKX1 gene will be an potential genetic target, with which, we can genetically manipulate the secondary wall synthesis in unicellular cotton fibers.
•This study further optimized the BSA technology via using F2 and F2:3 populations.•An novel candidate gene, GhCKX1, for the fiber strength in cotton was firstly identified.•The GhCKX1 protein was verified as a positive regulator for the cell wall thickness of plants.•Newly develop InDel markers can be directly deployed to the molecular marker-assisted breeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chromosome segment substitution lines (CSSLs) are ideal materials for identifying genetic effects. In this study, CSSL MBI7561 with excellent fiber quality that was selected from BC
4
F
3:5
of CCRI45 ...(
Gossypium hirsutum
)
× Hai1
(
Gossypium barbadense
) was used to construct 3 secondary segregating populations with 2 generations (BC
5
F
2
and BC
5
F
2:3
). Eighty-one polymorphic markers related to 33 chromosome introgressive segments on 18 chromosomes were finally screened using 2292 SSR markers which covered the whole tetraploid cotton genome. A total of 129 quantitative trait loci (QTL) associated with fiber quality (103) and yield-related traits (26) were detected on 17 chromosomes, explaining 0.85–30.35% of the phenotypic variation; 39 were stable (30.2%), 53 were common (41.1%), 76 were new (58.9%), and 86 had favorable effects on the related traits. More QTL were distributed in the Dt subgenome than in the At subgenome. Twenty-five stable QTL clusters (with stable or common QTL) were detected on 22 chromosome introgressed segments. Finally, the 6 important chromosome introgressed segments (
Seg-A02-1, Seg-A06-1, Seg-A07-2, Seg-A07-3, Seg-D07-3
, and
Seg-D06-2
) were identified as candidate chromosome regions for fiber quality, which should be given more attention in future QTL fine mapping, gene cloning, and marker-assisted selection (MAS) breeding.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Macrophages and microglia can be polarized into the ...classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved in innate and adaptive immune responses. However, whether PD-1 is involved in the modulation of macrophage/microglial polarization is unknown. In this study, the mRNA levels of
pd1
gradually increased after SCI, and PD-1 protein was found in macrophages/microglia in injured spinal cord sections. PD-1 knockout (KO) mice showed poor locomotor recovery after spinal cord crushing compared with wild-type mice. M1-type macrophages/microglia accumulated in greater numbers in the injured spinal cord of PD-1-KO mice. Under polarized stimulation, induced expression of PD-1 occurred in cultured macrophages and microglia. PD-1 suppressed M1 polarization by reducing the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and promoted M2 polarization by increasing STAT6 phosphorylation. In PD-1-KO mice, the M1 response was enhanced via the activation of STAT1 and nuclear factor-kappa B. Furthermore, PD-1 played various roles in phagocytosis in macrophages and microglia. Therefore, our results suggest that PD-1 signaling plays an important role in the regulation of macrophage/microglial polarization. Thus, deregulated PD-1 signaling may induce the polarization of macrophages/microglia toward the M1 phenotype. Overall, our results provide new insights into the modulatory mechanisms of macrophage/microglial polarization, thereby possibly facilitating the development of new therapies for SCI via the regulation of macrophage/microglial polarization through PD-1 signaling.
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