Dynamics of Th17 cells and their role in Schistosoma japonicum infection in C57BL/6 mice

Background

The current knowledge of immunological responses to schistosomiasis, a major tropical helminthic disease, is insufficient, and a better understanding of these responses would support vaccine development or therapies to control granuloma-associated immunopathology. CD4⁺ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis. The induction of T helper (Th)1, Th2 and T regulatory (Treg) cells and their roles in schistosome infections are well-illustrated. However, little in vivo data are available on the dynamics of Th17 cells, another important CD4⁺ T cell subset, after Schistosoma japonicum infection or whether these cells and their defining IL-17 cytokine mediate host protective responses early in infection.

Methodology

Levels of Th17 and the other three CD4⁺ T cell subpopulations and the cytokines related to induction or repression of Th17 cell generation in different stages of S. japonicum infection were observed. Contrary to reported in vitro studies, our results showed that the Th17 cells were induced along with the Th1, Th2, Treg cells and the IFN-γ and IL-4 cytokines in S. japonicum infected mice. The results also suggested that S. japonicum egg antigens but not adult worm antigens preferentially induced Th17 cell generation. Furthermore, decreasing IL-17 with a neutralizing anti-IL-17 monoclonal antibody (mAb) increased schistosome-specific antibody levels and partial protection against S. japonicum infection in mice.

Conclusions

Our study is the first to report the dynamics of Th17 cells during S. japonicum infection and indicate that Th17 cell differentiation results from the integrated impact of inducing and suppressive factors promoted by the parasite. Importantly, our findings suggest that lower IL-17 levels may result in favorable host protective responses. This study significantly contributes to the understanding of immunity to schistosomiasis and may aid in developing interventions to protect hosts from infection or restrain immunopathology.     

Survivin在大肠癌中的表达及其与Bcl-2、P53的关系

目的:研究凋亡抑制因子Survivin蛋白在大肠癌中的表达及其与患者临床病理和预后的关系。检测大肠癌组织中Survivin的表达与Bcl-2,P53的表达的关系。方法:用免疫组织化学方法检测115例大肠癌组织中Survivin,Bcl-2及P53的蛋白表达,并对病例随访5年。结果:Survivin在大肠癌中的阳性表达率为74/115(64．3%)。正常肠黏膜组织不表达Survivin。Survivin与患者的临床病理特征无显著相关性(P＞0．05)。Survivin的表达率在Bcl-2阳性的患者明显高于Bcl-2阴性的患者(P＜0．001),但是和P53的表达无显著相关性(P＞0．05)。Survivin阳性的患者5年生存率明显低于Survivin阴性的患者(P=0．001)。结论:在大肠癌组织中检测Survivin对于肿瘤患者的预后以及基于抗凋亡机制的肿瘤靶向治疗都有很重要的意义。     

Characterizing the impacts of highway pavement in a newly planned greater bay area economic belt in China

The International Journal of Life Cycle Assessment - As an ambitious strategy of national interest in China and with an aim at achieving the ‘one-hour economic circle’ among Greater Bay...     

A Novel Optimization of Water-Soluble Compound Polysaccharides from Chinese Herbal Medicines by Quantitative Theory and Study on Its Characterization and Antioxidant Activities

The present study optimized the extraction characterization and antioxidant activities of water-soluble compound polysaccharides (CPs) from hawthorn, lotus leaf, Fagopyrum tataricum, semen cassiae, Lycium barbarum, and Poria cocos Chinese herbal medicines that have mass ratios of 4 : 2 : 2 : 1.5 : 1 : 1. The CPs yield equation was predicted using quantitative theory, to which a maximum CPs yield of 7.18±0.24 % under the following optimal extraction conditions: a water-to-raw material ratio of 30 mL/g, an extraction temperature of 65 °C, an extraction time of 45 min, and extraction mode ultrasonic-assistant extraction. CPs were consisted of Ara, Gal, Glc, Xyl, Man, GalA and GlcA in a molar ratio of 3.1 : 2.6 : 50.6 : 1.7 : 20.4 : 17.2 : 4.2. The HPGPC profiles and FT-IR spectra implied that CPs were heterogeneous acidic polysaccharides and possessed the β-d -pyranose configuration. Congo red test, CD spectrum and SEM revealed that CPs with three helix conformation showed a flocculent, granulous or sheet-like appearance. Furthermore, the relationships between antioxidant activity and concentration of CPs displayed significant positive correlation, and the scavenging abilities for DPPH, hydroxyl radical, ABTS, superoxide-anion radical and reducing power of CPs were 93.56±2.51 %, 84.03±1.69 %, 83.29±1.93 %, 37.49±1.93 % and 0.467±0.006 at a concentration of 4.0 mg/mL. Therefore, CPs could be applied as a potential natural antioxidant in pharmaceutical or functional food fields.     

Roles of alternative splicing in the functional properties of inner ear-specific KCNQ4 channels

The function of the KCNQ4 channel in the auditory setting is crucial to hearing, underpinned by the finding that mutations of the channel result in an autosomal dominant form of nonsyndromic progressive high frequency hearing loss. The precise function of KCNQ4 in the inner ear has not been established. However, recently we demonstrated that there is differential expression among four splice variants of KCNQ4 (KCNQ4_v1-v4) along the tonotopic axis of the cochlea. Alternative splicing specifies the outcome of functional channels by modifying the amino acid sequences within the C terminus at a site designated as the membrane proximal region. We show that variations within the C terminus of splice variants produce profound differences in the voltage-dependent phenotype and functional expression of the channel. KCNQ4_v4 lacks exons 9-11, resulting in deletion of 54 amino acid residues adjacent to the S6 domain compared with KCNQ4_v1. Consequently, the voltage-dependent activation of KCNQ4_v4 is shifted leftward by approximately 20 mV, and the number of functional channels is increased severalfold compared with KCNQ4_v1. The properties of KCNQ4_v2 and KCNQ4_v3 fall between KCNQ4_v1 and KCNQ4_v4. Because of variations in the calmodulin binding domains of the splice variants, the channels are differentially modulated by calmodulin. Co-expression of these splice variants yielded current magnitudes suggesting that the channels are composed of heterotetramers. Indeed, a dominant negative mutant of KCNQ4_v1 cripples the currents of the entire KCNQ4 channel family. Furthermore, the dominant negative KCNQ4 mutant stifles the activity of KCNQ2-5, raising the possibility of a global disruption of KCNQ channel activity and the ensuing auditory phenotype.     

Redox Targeting of Anatase TiO2 for Redox Flow Lithium‐Ion Batteries

Anatase TiO₂ is an extensively studied anode material for lithium‐ion batteries because of its superior capability of storing Li⁺ electrochemically. Here reversible lithium storage of TiO₂ is achieved chemically using redox targeting reactions. In the presence of a pair of redox mediators, bis(pentamethylcyclopentadienyl)cobalt (CoCp^* ₂) and cobaltocene (CoCp₂) in an electrolyte, TiO₂ and its lithiated form Li _x TiO₂ can be reduced and oxidized by CoCp^* ₂ and CoCp₂ ⁺, respectively, which accompany Li⁺ insertion and extraction, albeit without attaching the TiO₂ onto the electrode. The reversible chemical lithiation/delithiation and the involved phase transitions are unambiguously confirmed using density functional theory (DFT) calculations, UV‐vis spectroscopy, X‐ray photoelectron spectoscopy (XPS), and Raman spectroscopy. A redox flow lithium‐ion battery (RFLB) half‐cell is assembled and evaluated, which is a critical step towards the development of RFLB full cells.     

Phosphorylation and ubiquitination of dynamin-related proteins (AtDRP3A/3B) synergically regulate mitochondrial proliferation during mitosis

The balance between mitochondrial fission and fusion is disrupted during mitosis, but the mechanism governing this phenomenon in plant cells remains enigmatic. Here, we used mitochondrial matrix‐localized Kaede protein (mt‐Kaede) to analyze the dynamics of mitochondrial fission in BY‐2 suspension cells. Analysis of the photoactivatable fluorescence of mt‐Kaede suggested that the fission process is dominant during mitosis. This finding was confirmed by an electron microscopic analysis of the size distribution of mitochondria in BY‐2 suspension cells at various stages. Cellular proteins interacting with Myc‐tagged dynamin‐related protein 3A/3B (AtDRP3A and AtDRP3B) were immunoprecipitated with anti‐Myc antibody‐conjugated beads and subsequently identified by microcapillary liquid chromatography–quadrupole time‐of‐flight mass spectrometry (CapLC Q‐TOF) MS/MS. The identified proteins were broadly associated with cytoskeletal (microtubular), phosphorylation, or ubiquitination functions. Mitotic phosphorylation of AtDRP3A/AtDRP3B and mitochondrial fission at metaphase were inhibited by treatment of the cells with a CdkB/cyclin B inhibitor or a serine/threonine protein kinase inhibitor. The fate of AtDRP3A/3B during the cell cycle was followed by time‐lapse imaging of the fluorescence of Dendra2‐tagged AtDRP3A/3B after green‐to‐red photoconversion; this experiment showed that AtDRP3A/3B is partially degraded during interphase. Additionally, we found that microtubules are involved in mitochondrial fission during mitosis, and that mitochondria movement to daughter cell was limited as early as metaphase. Taken together, these findings suggest that mitotic phosphorylation of AtDRP3A/3B promotes mitochondrial fission during plant cell mitosis, and that AtDRP3A/3B is partially degraded at interphase, providing mechanistic insight into the mitochondrial morphological changes associated with cell‐cycle transitions in BY‐2 suspension cells.