A lithium-sulfur (Li-S) battery is regarded as the most promising candidate for next generation energy storage systems, because of its high theoretical specific capacity (1675 mA h g
−1
) and ...specific energy (2500 W h kg
−1
), as well as the abundance, low cost and environmental benignity of sulfur. However, the soluble polysulfides Li
2
S
x
(4 ≤
x
≤ 8) produced during the discharge process can cause the so-called "shuttle effect" and lead to low coulombic efficiency and rapid capacity fading of the batteries, which seriously restrict their practical application. Using porous materials as hosts to immobilize the polysulfides is proved to be an effective strategy. In this article, a dual functional cage-like metal-organic framework (Cu-MOF), Cu-TDPAT, combining the Lewis basic sites from the nitrogen atoms of the ligand H
6
TDPAT with the Lewis acidic sites from Cu(
ii
) open metal sites (OMSs), was employed as the sulfur host in a Li-S battery for lithium ions and polysulfide anions (S
x
2−
). In addition, the size of nano-Cu-TDPAT was also optimized by microwave synthesis to reduce the internal resistance of the batteries. The electrochemical test results showed that the optimized Cu-TDPAT material can efficiently confine the polysulfides within the MOF, and the resultant porous S@Cu-TDPAT composite cathode material with the size of 100 nm shows good cycling performance with a reversible capacity of about 745 mA h g
−1
at 1C (1C = 1675 mA g
−1
) after 500 cycles, to the best of our knowledge, which is higher than those of all reported S@MOF cathode materials. The DFT calculation and XPS data indicate that the good cycling performance mainly results from the dual functional binding sites (that is, Lewis acid and base sites) in nanoporous Cu-TDPAT, providing the comprehensive and robust interaction with the polysulfides to overcome their dissolution and diffusion into the electrolyte. Clearly, our work provides a good example of designing MOFs with suitable interaction sites for the polysulfides to achieve S@MOF cathode materials with excellent cycling performance by multiple synergistic effects between nanoporous host MOFs and the polysulfides.
Cu-MOF with the dual functional binding sites is a very powerful MOF host for the inclusion of sulfur and polysulfides, demonstrating the best performance among all reported S@MOF composite cathode materials so far.
Despite the existence of a large amount of actin in the axons, the concentration F-actin was quite low in the myelinated axons and almost all the F-actin were located in the peripheries of the ...myelinated axons. Until now, the ultrastructural localization of F-actin has still not been reported in the myelinated axons, probably due to the lack of an appropriate detection method. In the present study, a phalloidin-based FITC-anti-FITC technique was adopted to investigate the subcellular localization of F-actin in the myelinated axons. By using this technique, F-actin is located in the outer and inner collars of myelinated cytoplasm surrounding the intermodal axon, the Schmidt-Lanterman incisures, the paranodal terminal loops and the nodal microvilli. In addition, the satellite cell envelope, which encapsulates the axonal initial segment of the peripheral sensory neuron, was also demonstrated as an F-actin-enriched structure. This study provided a hitherto unreported ultrastructural view of the F-actin in the myelinated axons, which may assist in understanding the unique organization of axonal actin cytoskeleton. KEY WORDS: Axon; F-actin; Electron microscopy; Myelin sheath; Rat.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hedyotis hedyotidea has been used in traditional Chinese medicine for the treatment of autoimmune diseases. However, the mechanisms underlying for the effect remain unknown. We previously showed ...that, among 11 compounds extracted from H hedyotidea, betulin produced the strongest suppressive effect on T cell activation. Here, we examined the hepatoprotective effects of betulin against acute autoimmune hepatitis in mice and the mechanisms underlying the effects. Freshly isolated mouse splenocytes were stimulated with concanavalin A （Con A, 5 pg/mL） in the presence of betulin, the cell proliferation was assessed with CSFE-dilution assay. Mice were injected with betulin （10, 20 mg.kg-1.d-1, ip） for 3 d. One hour after the last injection, the mice were injected with Con A （15 mg/kg, iv） to induce acute hepatitis. Blood samples and liver tissues were harvested at 10 h after Con A injection, and serum transaminase levels and liver histopathology were detected; serum levels of proinflammatory cytokines, hepatic T lymphocyte ratios, and functional statuses of conventional T and NKT cells were also analyzed. Betulin （16 and 32 μmol/L） dose-dependently suppressed the proliferation of Con A-stimulated mouse splenocytes in vitro. In Con A-challenged mice, preinjection with betulin （20 mg.kg-1.d-1） significantly decreased the levels of proinflammatory cytokines IFN-γ, TNF-α and IL-6, and ameliorated liver injury. Furthermore, pretreatment with betulin （20 mg-kg-1.d-1） significantly inhibited the Con A-induced activation of NKT and conventional T cells, and decreased production of proinflammatory cytokines IFN-γ, TNF-α and IL-6 in these two cell populations. Betulin has immunornodulatory effect on overly activated conventional T and NKT cells and exerts hepatoprotective action in mouse autoimmune hepatitis. The findings provide evidence for the use of H hedyotidea and its constituent betulin in the treatment of autoimmune diseases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chromosome identification and karyotype using fluorescence in situ hybridization (FISH) provides a technical platform for genome and cytogenetic studies. Brassica juncea (brown mustard, 2n=4×=36; ...genome AABB) is an allopolyploid species that originated from a spontaneous hybridization of Brassica rapa and Brassica nigra and contains many valuable traits. In this study, a multicolor FISH procedure allowing the identification of all 18 chromosomal pairs was developed by two-step hybridizations with probes on the same metaphase chromosomes. The distribution patterns and chromosomal localizations of six repeat sequences (satellite repeat pBrSTR, 5S rDNA, 45S rDNA, B genome-specific repeat pBNBH35, and centromeric satellite repeats CentBr1 and CentBr2) on B. juncea chromosomes were characterized. Comparative karyotype analyses showed that the genome is relatively stable in comparison with its diploid progenitor species and revealed intraspecific karyotypic diversity among three accessions of B. juncea. This study provides valuable information about the genome evolution of B. juncea and a toolkit that will be helpful for chromosome identification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rechargeable lithium–metal batteries with a cell‐level specific energy of >400 Wh kg−1 are highly desired for next‐generation storage applications, yet the research has been retarded by poor ...electrolyte–electrode compatibility and rigorous safety concerns. We demonstrate that by simply formulating the composition of conventional electrolytes, a hybrid electrolyte was constructed to ensure high (electro)chemical and thermal stability with both the Li‐metal anode and the nickel‐rich layered oxide cathodes. By employing the new electrolyte, Li∥LiNi0.6Co0.2Mn0.2O2 cells show favorable cycling and rate performance, and a 10 Ah Li∥LiNi0.8Co0.1Mn0.1O2 pouch cell demonstrates a practical specific energy of >450 Wh kg−1. Our findings shed light on reasonable design principles for electrolyte and electrode/electrolyte interfaces toward practical realization of high‐energy rechargeable batteries.
Formulation of conventional electrolyte composition yields a hybrid solid/liquid electrolyte that is electrochemically compatible with the Li‐metal anode and the nickel‐rich layered oxide cathodes, which promises stable operation of a practical 10‐Ah‐grade pouch cell with a specific energy of >450 Wh kg−1.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
AIM： To recognize cystic neoplasia of the pancreas and thus to identify a panel of curable diseases.
METHODS： Sixty-four cases of cystic neoplasia of the pancreas, including 28 cases of intraductal ...papillary mucinous neoplasia （IPMN）, 12 cases of serous cystic neoplasia （SCN）, 11 cases of mucinous cystic neoplasia （MCN）, 11 cases of solid pseudo-papillary neoplasia （SPN）, and 2 cases of solid tumor with cystic degeneration were examined immunohistochemically for their expression of MUC1, MUC2, MUC4, MUC5AC, and MUC6, as well as other related antigens.
RESULTS： Adenoma type of IPMN and borderline lesions exhibited high expressions of MUC2, and MUC5AC. In contrast, IPMN with invasive carcinoma component showed MUC1 immunoreactivity. SCN was mainly positive for MUC1 and MUC6, while negative for MUC2, MUC4 and MUC5AC. Noninvasive MCN, regardless of its cellular atypia degree, was positive for MUC5AC and negative for MUC1. MUC1 expression was only observed in patients with an invasive component. No mucin expression was found in SPN.
CONCLUSION： Mucin profile may, in conjunction with histologic study, provide important information on tumor types and patient treatment of cystic neoplasia of the pancreas.
G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to ...biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel single-chain variable fragment (scFv) antibody, D1, with high binding selectivity for parallel G-quadruplexes in vitro and in vivo. Genome-wide chromatin immunoprecipitation using D1 and deep-sequencing revealed the consensus sequence for parallel G-quadruplex formation, which is characterized by G-rich sequence with a short loop size (<3 nt). By using D1, telomeric parallel G-quadruplex was identified and its formation was regulated by small molecular ligands targeting and telomere replication. Together, parallel G-quadruplex specific antibody D1 was found to be a valuable tool for determination of G-quadruplex and its conformation, which will prompt further studies on the structure of G-quadruplex and its biological implication in vivo.
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•A new antibody with parallel G-quadruplex specific recognition•Consensus sequence for parallel G-quadruplex formation on the human genome•Identification of parallel G-quadruplex formation at telomeres•Modulation of telomeric parallel G-quadruplex formation in human cell
G-quadruplex conformation in vivo is difficult to assay, especially for telomeric G-quadruplexes. Liu et al. demonstrate the parallel G-quadruplex consensus sequence on the genome and identify the regulated formation of parallel quadruplex at telomeres by using a new antibody.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising ...drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chromosome ten (PTEN) deficiency promotes protein synthesis and proteasome subunit expression and proteolytic activity, creating a dependency on the proteasome for cancer cell growth and survival. Thus, targeting the proteasome machinery with the inhibitor bortezomib inhibited the proliferation and survival of CCA cells lacking functional PTEN. Therapeutic evaluation of PDXs, autochthonous mouse models, and patients confirmed this dependency on the proteasome. Mechanistically, we found that PTEN promoted the nuclear translocation of FOXO1, resulting in the increased expression of
and
BACH1 and MAFF are transcriptional regulators that recognize the antioxidant response element, which is present in genes encoding proteasome subunits. PTEN induced the accumulation and nuclear translocation of these proteins, which directly repressed the transcription of genes encoding proteasome subunits. We revealed that the PTEN-proteasome axis is a potential target for therapy in PTEN-deficient CCA and other PTEN-deficient cancers.
Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested ...conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs)
in vitro
, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and
in vivo
by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1β, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.
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