Stochastic processes regulate belowground community assembly in alpine grasslands on the Tibetan Plateau

Understanding biogeographical patterns and underlying processes of belowground community assembly is crucial for predicting soil functions and their responses to global environmental change. However, little is known about potential differences of belowground community assembly among bacteria, fungi, protists and soil animals, particularly for alpine ecosystems. Based on the combination of large-scale field sampling, high-throughput marker-gene sequencing and multiple statistical analyses, we explored patterns and drivers of belowground community assembly in alpine grasslands on the Tibetan Plateau. Our results revealed that the distance–decay rates varied among trophic levels, with organisms of higher trophic level having weaker distance–decay pattern. The spatial and environmental variables explained limited variations of belowground communities. By contrast, the stochastic processes, mainly consisting of dispersal limitation and drift, played a primary role in regulating belowground community assembly. Moreover, the relative importance of stochastic processes varied among trophic levels, with the role of dispersal limitation weakening whereas that of drift enhancing in the order of bacteria, fungi, protists and soil animals. These findings advance our understanding of patterns and mechanisms driving belowground community assembly in alpine ecosystems and provide a reference basis for predicting the dynamics of ecosystem functions under changing environment.     

Nanostructures from the self‐assembly of α‐helical peptide amphiphiles

Self‐assembly of PAs composed of palmitic acid and several repeated heptad peptide sequences, C₁₅H₃₁CO‐(IEEYTKK)_n‐NH₂ (n = 1–4, represented by PA1–PA4), was investigated systematically. The secondary structures of the PAs were characterized by CD. PA3 and PA4 (n = 3 and 4, respectively) showed an α‐helical structure, whereas PA1 and PA2 (n = 1 and 2, respectively) did not display an α‐helical conformations under the tested conditions. The morphology of the self‐assembled peptides in aqueous medium was studied by transmission electron microscopy. As the number of heptad repeats in the PAs increased, the nanostructure of the self‐assembled peptides changed from nanofibers to nanovesicles. Changes of the secondary structures and the self‐assembly morphologies of PA3 and PA4 in aqueous medium with various cations were also studied. The critical micelle concentrations were determined using a pyrene fluorescence probe. In conclusion, this method may be used to design new peptide nanomaterials. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

One of the theories regarding oral carcinogenesis is that the tumor growth is initiated from cancer stem cells (CSCs) that self-renew and give rise to differentiated tumor cells, like stem cells do in normal tissues. The most common methods of CSC identification are based on CSC marker expression in carcinogenesis. This study examined the expression of CD133 and CD44, the most commonly used CSC biomarkers in oral squamous cell sarcoma (SCC), with the goal of identifying molecular biomarkers whose expression is associated with the multistep oral carcinogenesis. The expression of CD133, CD44, proliferating cell nuclear antigen (PCNA), and Cytokeratin (CK) was examined by Western blot analysis and confirmed by immunohistochemistry in a 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis model. Also, the expression of aldehyde dehydrogenase 1 (ALDH1), OCT-4 and Nanog were investigated for alteration of cancer cell stemness by Western blot. Along with the progress of multistep carcinogenesis, there were slight increases of CD133 and CD44 expression in the dysplasia group compared with normal rats. However, CD133 protein level was significantly overexpressed in SCC. The expression of PCNA and CK were low in normal group, but sequentially increased in SCC. ALDH1, Nanog and OCT-4 expression were significantly increased according to SCC grade during carcinogenesis. The findings indicate that CD133 is useful in identifying oral CSCs, which suggests that CD133 may serve as a predictor to identify CSCs with a high risk of oral cancer development.     

Sensitization by Pulmonary Reactive Oxygen Species of Rat Vagal Lung C-Fibers: The Roles of the TRPV1, TRPA1, and P2X Receptors

Sensitization of vagal lung C-fibers (VLCFs) induced by mediators contributes to the pathogenesis of airway hypersensitivity, which is characterized by exaggerated sensory and reflex responses to stimulants. Reactive oxygen species (ROS) are mediators produced during airway inflammation. However, the role of ROS in VLCF-mediated airway hypersensitivity has remained elusive. Here, we report that inhalation of aerosolized 0.05% H₂O₂ for 90 s potentiated apneic responses to intravenous capsaicin (a TRPV1 receptor agonist), α,β-methylene-ATP (a P2X receptor agonist), and phenylbiguanide (a 5-HT₃ receptor agonist) in anesthetized rats. The apneic responses to these three stimulants were abolished by vagatomy or by perivagal capsaicin treatment, a procedure that blocks the neural conduction of VLCFs. The potentiating effect of H₂O₂ on the apneic responses to these VLCF stimulants was prevented by catalase (an enzyme that degrades H₂O₂) and by dimethylthiourea (a hydroxyl radical scavenger). The potentiating effect of H₂O₂ on the apneic responses to capsaicin was attenuated by HC-030031 (a TRPA1 receptor antagonist) and by iso-pyridoxalphosphate-6-azophenyl-2′,5′-disulphonate (a P2X receptor antagonist). The potentiating effect of H₂O₂ on the apneic responses to α,β-methylene-ATP was reduced by capsazepine (a TRPV1 receptor antagonist), and by HC-030031. The potentiating effect of H₂O₂ on the apneic responses to phenylbiguanide was totally abolished when all three antagonists were combined. Consistently, our electrophysiological studies revealed that airway delivery of aerosolized 0.05% H₂O₂ for 90 s potentiated the VLCF responses to intravenous capsaicin, α,β-methylene-ATP, and phenylbiguanide. The potentiating effect of H₂O₂ on the VLCF responses to phenylbiguanide was totally prevented when all antagonists were combined. Inhalation of 0.05% H₂O₂ indeed increased the level of ROS in the lungs. These results suggest that 1) increased lung ROS sensitizes VLCFs, which leads to exaggerated reflex responses in rats and 2) the TRPV1, TRPA1, and P2X receptors are all involved in the development of this airway hypersensitivity.     

Retrospective Evaluation of New Chinese Diagnostic Scoring System for Disseminated Intravascular Coagulation

Objectives

To retrospectively validate the new Chinese DIC scoring system (CDSS).

Methods

This study retrospectively collected the information of 619 patients (371 cases with non-hematologic malignancies, 248 cases with hematologic malignancies) who suspected of DIC in Wuhan Union Hospital during 2013-4 to 2014-6. We validated CDSS by comparing it with three leading scoring systems, from International Society on Thrombosis and Haemostasis (ISTH), Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW), and evaluated its prognostic value by 28 days mortality, APACHE II and SOFA score.

Results

In non-hematologic malignancies, CDSS was more specific than JAAM (72.55% vs. 50.49%, p<0.05) and more sensitive than ISTH (77.07% vs. 62.03%, p<0.05). In hematologic malignancies, the area under the ROC curve of CDSS was larger than ISTH and JMHW (0.933 vs. 0.889, p<0.01 with ISTH, 0.944 vs. 0.845, p<0.01 with JMHW). In addition, the 28-day mortality rate, SOFA scores, APACHE II scores of DIC patients diagnosed by CDSS were significantly greater than non-DIC (P <0.05).

Conclusions

We are the first group to propose CDSS. It emphasized the values of the clinical manifestations, the rapidly declining platelet count, APTT in the diagnosis of DIC and used D-dimer as the fibrin-related maker. DIC with hematological malignancies was treated as a special part. In this study we can see that CDSS displayed an acceptable property for the diagnosis of DIC with appropriate sensitivity and specificity, and also had a good prognostic value for DIC patients.     

p38-MAPK信号通路在HHPH中的作用及三七总皂苷干预

目的:研究p38-MAPK信号通路在大鼠低O2高CO2性肺动脉高压(HHPH)发生发展中的动态变化;探讨三七总皂苷(PNS)防治低O2高CO2性肺动脉高压的机制。方法:复制慢性HHPH大鼠模型,分为正常组(N),低O2高CO23 d组(H3d)、1周组(H1w)、2周组(H2w)、4周组(H4w),及PNS治疗组(Hp),Hp组腹腔注射血塞通注射液(成分为PNS和生理盐水)。Western印迹法、免疫组织化学技术检测肺组织及肺血管P-p38、p38蛋白的表达。结果:①H1w、H2w、H4w和Hp组的WA/TA均高于N组(P均<0.05),但H3d组较N组增加不明显(P>0.05),Hp组WA/TA明显低于H4w组(P<0.05)。②肺组织P-p38蛋白在N组表达不明显,在H3d、H1w、H2w、H4w组均有高水平表达。③肺小动脉壁P-p38蛋白在N组和H3d组表达呈阴性或弱阳性,在H1w、H2w、H4w组有高水平表达,较N组差异有统计学意义(P<0.05)。④Hp组肺组织P-p38,肺小动脉壁P-p38蛋白表达较低O2高CO2组降低(P<0.05)。结论:p38-MAPK信号通路介导了大鼠HHPH的形成。PNS可减轻这一过程,其机制可能和PNS抑制P-p38表达有关。     

Eradication of hepatoma and colon cancer in mice with Flt3L gene therapy in combination with 5-FU

We developed a recombinant defective adenovirus with an insert of gene encoding extracellular domain of mouse Flt3L (Ad-mFlt3L) under control of cytomegalovirus promoter to investigate the biological efficacy of Flt3L in combination with chemotherapeutical drug, 5-FU, in eliciting an effective anti-cancer immunity in mouse hepatoma and colon cancer model systems. The constructed Ad-mFlt3L efficiently infected hepatoma and colon cancer cells both in vitro and in vivo, leading to a high production of mFlt3L proteins in association with accumulation of DCs, NK cells and lymphocytes in local tumor tissues. Administration of Ad-mFlt3L can protect bone marrow injury caused by 5-Fu and stimulates proliferation and maturation of lymphocytes, APCs and NKs. Intratumoral injection of Ad-mFlt3L followed by an intraperitoneal administration of 5-Fu significantly inhibited tumor growth and cured established tumors. Adenovirus mediated Flt3L gene therapy synergies with chemotherapeutic drug, 5-Fu, in elicitation of long-lasting antitumor immunity. The tumor specific immunity can be adoptively transferred into naïve animals successfully by transfusion of CD3⁺CD8⁺ T cells from the treated mice. The data suggests that adenovirus mediated Flt3L gene therapy in combination with 5-Fu chemotherapy may open a new avenue for development of anti-cancer chemogenetherapy.     

Design,synthesis, and biological evaluation of triazole-pyrimidine-methylbenzonitrile derivatives as dual A2A/A2B adenosine receptor antagonists

A series of novel dual A_2A/A_2B AR antagonists based on the triazole-pyrimidine-methylbenzonitrile core were designed and synthesised. The A_2A AR antagonist cAMP functional assay results were encouraging for most target compounds containing quinoline or its open-ring bioisosteres. In addition, compound 7i displayed better inhibitory activity on A_2B AR (IC₅₀ 14.12 nM) and higher potency in IL-2 production than AB928. Moreover, molecular docking studies were carried out to explain the rationality of molecular design and the activity of compound 7i. Further studies on 7f and 7i revealed good liver microsomes stabilities and acceptable in vivo PK profiles. This study provides insight into the future development of dual A_2A/A_2B AR antagonists for cancer immunotherapy.     

臭味假单胞菌邻苯二酚1,2—双加氧酶的制备和一般性质

Catechol-1,2-dioxygenase (EC 1.13.11.1) catalyzes the degradation of catechol to cis, cis-muconic acid. The biochemical properties of catechol-1,2-dioxygenase from Pseudomonas putida 84103 were investigated. The optimum pH and temperature is 7.5-8.0 and 25-30 degrees C, respectively. Cu2+, Zn2+ inhibit the enzyme activity. The paper chromatograph and UV absorption spectrum of enzymatic reaction product are accordance with those of the standard muconic acid.