The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2％DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13-15 million years ago (MYA) and another about 125-142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages-lycophytes and seed plants-of vascular plants.
Evolution, Molecular ; Genome, Plant ; Genomics ; Phylogeny ; Polyploidy ; Selaginellaceae/genetics*

Objective To find the differentially expressed long non-coding RNA (lncRNA) between db/db mice that with nephropathy (DN) or not (DM).Methods In this study,3 DM db/db mice and 2 DN db/db mice proven by renal biopsy were randomly selected,and 3 healthy db/m mice as normal control group.Then,differentially expressed lncRNAs,mRNAs and their fragments per kilobase million (FPKM) in kidney samples were detected by high-throughput next generation sequencing technology.Sequencing data were analyzed to filter out the differentially expressed lncRNA,and theirfunction was preliminarily investigated by bioinformatics analysis and functional enrichment analysis to predict their target genes.Total RNAs of kidneys from these 8 mice were extracted to run real time PCR (RT-qPCR) for verifying the outcomes of the high-throughput sequencing.Results The urinary microalbumin/creatinine ratio (UACR),serum creatinine,and glomerular basement membrane thickness of DN db/db mice were higher than those of DM db/db mice (all P ＜ 0.05),while there was not significant difference in glucose between DM and DN mice.Totally 160 lncRNAs were up-regulated and 99 lncRNAs were down-regulated in kidneys of DN mice compared with those of DM mice,in which the differentially expressed lncRNAs with FPKM value≥2 and differential expression≥ 1 fold between groups were screened and verified by RT-qPCR.Finally three lncRNAs whose variation trend were consistent with the outcomes of the high-throughput sequencing were obtained.Conclusion There was a significantly different expression pattern of lncRNA between the kidneys of DN and DM mice,which may be involved in the progress of DN.

Objective To observe image quality and impact factors for single heart beat coronary CTA (CCTA) with prospectively ECG-triggered CT in patients with low,high heart rate (HR) and arrhythmia.Methods Single heart-beat CCTA was performed for 208 patients with prospectively ECG-triggered 256-slice wide-detector CT without drug control of HR.The patients were divided into 3 groups,including low HR group (n=87,HR≤70 bpm),high HR group (n=38,HR＞70 bpm) and arrhythmia group (n=83,HR variation ＞ 10 bpm in 5 cardiac cycles).The normal reconstruction phase was set as 75％ or 45％ in R-R interval,while the optimal phase was that with the least motion artifacts.Univariate linear regression was used to analyze the impact factors for image quality.Results Compared with images of normal phase,the optimal phase of 105 patients (105/208,50.48％) was altered.In the optimal images,imaging quality,SNR and CNR were not significantly different among 3 groups (all P＞0.05).Image quality was significantly influenced by reconstruction phase and artifact type (both P＜0.001).Conclusion During prospectively ECG-triggered 256-slice wide-detector CCTA without drug control of HR,high HR and arrhythmia are not significant impact factors of image quality.

Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR),as well as the feasibility for surveillance of tumor targeting with MRI.Methods Nanoparticles (NPs)of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared,and the morphology of nanoparticles was observed with transmission electron microscope (TEM).The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI.MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro.The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM.Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI,decreased significantly compared with PEG-SPIO.The rate of signal intensity change was -58.2％,-82.7％,-94.4％ and-98.3％,respectively,at iron concentrations of (0,10,20,40,80 μg/ml) of antiEGFR-PEG-SPIO.Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells,but few of PEG-SPIO.Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro,and the targeting delivery process could be monitored with 3.0T MRI.

OBJECTIVE:To evaluate the effect of clinical antibiotics use special rectification in our hospital. METHODS:100 discharged medical records of typeⅠincision surgery were randomly sampled from our hospital during May in 2010 to Apr. in 2011,May in 2011 to Apr. in 2012,May in 2012 to Apr. in 2013,May in 2013 to Apr. in 2014,totaling 400 records. And then evaluation indicators were analyzed statistically,such as antibiotics use intensity,perioperative DDDs of antibiotics in typeⅠinci-sion surgery,DUI,types of antibiotics during perioperative period,medication time,etc. RESULTS:Since the implementation of clinical antibiotics use special rectification in May 2011,the utilization ratio of antibiotics in typeⅠincision surgery of our hospital decreased from 96% to 33%;DUI decreased from 1.44 to 0.79;while reasonable rate of drug selection increased from 19.8% to 100%,and that of medication time increased from 43.8% to 100%. CONCLUSIONS:Rational medication evaluation indicators in typeⅠincision surgery of our hospital have been improved after the implementation of clinical antibiotics use special rectification.

ObjectiveTo measure the changes of eye shape and axial length of the eyeball before and after removing the scleral encircling buckles. MethodsThis is a prospective and controlled study. Twenty eyes (20 patients) with rhegmatogenous retinal detachment and the fellow eyes were enrolled in this study.All patients underwent scleral encircling buckling, and the buckles were removed 2.0 - 3.5 years after the surgery. The eye shape and axial length of both eyes were measured by three-dimensional computed tomography (3D-CT) before and one, three, six months after the removing surgery. The axial length was also measured by intraocular lens (IOL)-Master. Results3D-CT showed that buckled eyeball depressed at the equator, resulting in a gourd-shaped eyeball.One month after removing the encircling buckle the depression disappeared.By 3D-CT scanning, the axial lengths of buckled eyes were (27.65 ± 1.22),(27. 3±1.56), (27. 29 ± 1.46) and (27. 12 ± 1.49) mm before and one, three, six months after the removing surgery respectively.The difference betweenbefore and after removing surgery was not statistically significant(t=2.89, P = 0.723). By IOL-Master, the axial length of operated eyes were (28. 32± 1.94), (28.17± 1.87), (28.21± 1.94), (28.25± 1.93) mm respectively.The difference between before and after removing the encircling band was not statistically significant (t = 3. 304, P =0.93). There was no significant difference in these two measuring modes (t= 3.705, P = 0.847).ConclusionsEncircling buckling can cause eyeball indentation, removing the encircling band can rescue the indentation. There are no changes in the axial length before and after removing the encircling buckles.