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Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.

Recently, extensive discoveries have suggested that the F-actin capping protein α1 subunit (CAPZA1) in various human tumors could elicit significantly important parts in regulating cell proliferation, metastasis and epithelial-mesenchymal transition. However, the immune-regulating role of CAPZA1 in the initiation and development of Lung adenocarcinoma (LUAD) remains incompletely clear. In our research, we firstly found that CAPZA1 serves as an oncogene in pan-cancers from TCGA data and higher CAPZA1 expression process unfavorably prognostic value in LUAD based on Starbase database and PrognoScan database. Then, in our analyses, lncRNAs AC026356.1 in LUAD acts as a competitive endogenous RNA (ceRNA) of miR-30d-5p, which might be the possible regulatory miRNA of CAPZA1 based on the Starbase database. Finally, we confirmed that CAPZA1 expression had a tightly positive correlation with immune infiltration cells, immune infiltration markers, TMB, MSI, immune score, stromal score, and immune checkpoints, indicating that CAPZA1 was a markedly reliable therapeutic target for immunological antitumor strategy. In conclusion, our investigations unveiled that CAPZA1 might function as an immune-associated biomarker in the development and treatment of LUAD, thereby acting as a promising prognostic and therapeutic target against LUAD.

Lysine-specific demethylase1 (LSD1), an important class of histone demethylases, plays a crucial role in regulation of mammalian biology. The up-regulated LSD1 expression was frequently associated with progress and oncogenesis of multiple human cancers, including non-small cell lung cancer (NSCLC). Therefore, inhibition of LSD1 may provide an attractive strategy for cancer treatment. We investigated the effect of sanguinarine against lung cancer cells as a natural alkaloid LSD1 inhibitor.The inhibition properties of sanguinarine to the recombinant LSD1 were evaluated by a fluorescence-based method. Subsequently, assays such as viability, apoptosis, clonogenicity, wound healing, and transwell were performed on H1299 and H1975 cells after treatment with sanguinarine.Upon screening our in-house natural chemical library toward LSD1, we found that sanguinarine possessed a potent inhibitory effect against LSD1 with the IC50 value of 0.4 μM in a reversible manner. Molecular docking simulation suggested that sanguinarine may inactivate LSD1 by inserting into the binding pocket of LSD1 to compete with the FAD site. In H1299 and H1975 cells, sanguinarine inhibited the demethylation of LSD1, validating its cellular activity against the enzyme. Further studies showed that sanguinarine exhibited a strong capacity to suppress colony formation, inhibit migration and invasion, as well as induce apoptosis of H1299 and H1975 cells.Our findings present a new chemical scaffold for LSD1 inhibitors, and also provide new insight into the anti-NSCLC action of sanguinarine.

Hemangioblastoma (HB) is an abnormal intracranial buildup of blood vessels that exhibit a great potential for hemorrhage. Surgical options are limited, and few medications are available for treatment. We show here by immunohistochemical analysis that HB lesions display highly increased levels of VEGF expression and macrophage/microglia infiltration compared with those in normal brain tissues. In the meantime, TNF superfamily 15 (TNFSF15) (also known as vascular endothelial growth inhibitor), an antiangiogenic cytokine, is highly expressed in normal brain blood vessels but diminished in HB lesions. We set up a brain hemangioma model by using mouse bEnd.3 cells of a T antigen-transformed endothelial cell line that produce a large amount of VEGF. When implanted in mouse brains, these cells form lesions that closely resemble the pathologic characteristics of HB. Retroviral infection of bEnd.3 cells with TNFSF15 leads to inhibition of VEGF production and retardation of hemangioma formation. Similar results are obtained when wild-type bEnd.3 cells are implanted in the brains of transgenic mice overexpressing TNFSF15. Additionally, TNFSF15 treatment results in enhanced pericyte coverage of the blood vessels in the lesions together with reduced inflammatory cell infiltration and decreased hemorrhage. These findings indicate that the ability of TNFSF15 to counterbalance the abnormally highly angiogenic and inflammatory potential of the microenvironment of HB is of therapeutic value for the treatment of this disease.-Yang, G.-L., Han, Z., Xiong, J., Wang, S., Wei, H., Qin, T.-T., Xiao, H., Liu, Y., Xu, L.-X., Qi, J.-W., Zhang, Z.-S., Jiang, R., Zhang, J., Li, L.-Y. Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15.

Summary Given the rapid increase in the prevalence of chronic diseases in aging populations, this prospective study including 17 707 adults aged ≥45 years from China Health and Retirement Longitudinal Study was used to estimate the associations between chronic disease, multimorbidity, and depression among middle-aged and elderly adults in China, and explore the mediating factors. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) questionnaire. Twelve chronic physical conditions, including hypertension, diabetes, dyslipidemia, cancer, chronic lung disease, liver disease, heart failure, stroke, kidney disease, arthritis or rheumatism, asthma, digestive disease were assessed. The prevalence rates for physical multimorbidity and depression (CES-D-10 ≥10) were 43.23% and 36.62%, respectively. Through multivariable logistic models and generalized estimating equation (GEE) models, we found all 12 chronic physical conditions, and multimorbidity were significantly associated with depression. Both mobility problems and chronic pain explained more than 30% of the association for all chronic conditions, with particularly high percentages for stroke (51.56%) and cancer (51.06%) in mobility problems and cancer (53.35%) in chronic pain. Limited activities of daily living (ADL) explained 34.60% of the stroke-cancer relationship, while sleep problems explained between 10.15% (stroke) and 14.89% (chronic lung disease) of the association. Individuals with chronic diseases or multimorbidity are significantly more likely to be depressed. Functional symptoms involving limitations of ADL and mobility difficulties mediated much of the association between chronic diseases and incident depression. These symptoms could be targeted for interventions to ameliorate the incidence of depression among individuals with chronic conditions.

Vascular hyperpermeability is critical in ischemic diseases, including stroke and myocardial infarction, as well as in inflammation and cancer. It is well known that the VEGF-VEGFR2 signaling pathways are pivotal in promoting vascular permeability; however, counterbalancing mechanisms that restrict vascular permeability to maintain the integrity of blood vessels are not yet fully understood. We report that TNF superfamily member 15 (TNFSF15), a cytokine largely produced by vascular endothelial cells and a specific inhibitor of the proliferation of these same cells, can inhibit VEGF-induced vascular permeability in vitro and in vivo, and that death receptor 3 (DR3), a cell surface receptor of TNFSF15, mediates TNFSF15-induced dephosphorylation of VEGFR2. Src homology region 2 domain-containing phosphatase-1 (SHP-1) becomes associated with DR3 upon TNFSF15 interaction with the latter. In addition, a protein complex consisting of VEGFR2, DR3, and SHP-1 is formed in response to the effects of TNFSF15 and VEGF on endothelial cells. It is plausible that this protein complex provides a structural basis for the molecular mechanism in which TNFSF15 induces the inhibition of VEGF-stimulated vascular hyperpermeability.-Yang, G.-L., Zhao, Z., Qin, T.-T., Wang, D., Chen, L., Xiang, R., Xi, Z., Jiang, R., Zhang, Z.-S., Zhang, J., Li. L.-Y. TNFSF15 inhibits VEGF-stimulated vascular hyperpermeability by inducing VEGFR2 dephosphorylation.

Transformation of normalized radar cross section (NRCS) in HH-polarization to that in VV-polarization NRCS is essential step to retrieve sea surface wind speed from SAR data when the Geophysical Model Function (GMF) is applied. In this paper, four different Polarization Ratio (PR) models including Mouche-PR1 model, Mouche-PR2 model, Zhang-PR model, and Liu-PR model are combined with the GMF CMOD5.N to retrieve sea surface wind speed from 130 HH-polarized Sentinel-1 SAR images. The results suggest that wind speeds retrieved using the Zhang-PR model agree better with the National Data Buoy Center (NDBC) buoy measurements and ERA-Interim reanalysis model dataset of the European Centre for Medium-Range Weather Forecasting (ECMWF) than the other three models. Compared to the buoy measurements, the root mean square error (RMSE) and scatter index (SI) of wind speed retrieved by the Zhang-PR model are 1.60m/s and 22.40% , respectively, while compared to the ERA-Interim model results the RMSE and SI are 2.30m/s and 30.03% , respectively. It is suggested that the Zhang-PR model combined with the CMOD5.N function has a potential application in retrieving sea surface wind speed from Sentinel-1 images acquired at HH-polarization.

Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) are two of the most notable driver genes in lung cancer, whilst vascular endothelial growth factor (VEGF) signaling serves a critical function in tumor angiogenesis. However, few studies have focused on the potential connection between EGFR/KRAS mutational status, and VEGFA, VEGF receptor (VEGFR)1 and VEGFR2 expression in lung adenocarcinoma. EGFR (exon 19, 20 and 21) and KRAS (exon 2) mutations were detected using an amplification refractory mutation system technique, and the expression of VEGFA, VEGFR1 and VEGFR2 was analyzed using immunohistochemistry in 204 patients with lung adenocarcinoma. Associations between EGFR/KRAS mutational status and VEGFA, VEGFR1, and VEGFR2 expression was analyzed using Pearson χ2 tests. It was revealed that EGFR 21 exon (P=0.033) and EGFR 20 exon (P=0.002) mutated tumors exhibited a significantly higher level of expression of VEGFA. EGFR 21 exon mutant tumors additionally demonstrated a significantly higher level of co-expression of VEGFA and VEGFR1 (P

Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor-C/D (VEGF-C/D) and VEGF receptor-3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF-C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium-derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up-regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain-containing receptor-3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15-DR3 interaction with a Tnfsf15 neutralizing antibody, 4-3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF-κB. Tnfsf15-overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild-type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4-3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up-regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema.

Activated carbon is heat-treated in a H2 atmosphere at 600, 800, and 1000 °C for 1 h, respectively, to be used as electrode material for electrical double layer capacitors (EDLCs). After heat treatment, the surface morphology has no obvious change as compared with the raw material. The specific surface area and pore volume of sample treated at 600 °C have a slightly increase while those of samples treated at higher temperature decrease. XPS and elemental analysis indicate that oxygen containing functional groups on the sample are significantly reduced after treatment. The electrochemical performance of samples was evaluated using cyclic voltammetry and galvanostatic charge–discharge tests in 1 M TEABF4/PC electrolyte. The sample treated at 600 °C shows the optimized electrochemical performance with increase capacitance, enhanced stability, and improved energy density. Its initial specific capacitance is near 127 F/g, and initial coulombic efficiency is about 52 %. At 3.0 V, its energy density reaches 32 Wh/kg and specific capacitance is about 70 F/g at 1 A/g even after 10,000 charge–discharge cycles. Thus, heat treatment at 600 °C under H2 atmosphere is an effective method to improve electrochemical properties of EDLCs based on activated carbon material.

4-Octylphenol (OP) was used to form self-assembled films on copper to inhibit its corrosion in 0.5 M HCl solution. The corrosion protection ability of the OP films was evaluated using potentiodynamic polarization and electrochemical impedance spectroscopy studies. It was found that the highest inhibition efficiency was obtained when copper was self-assembled in a 1.0 mM OP solution for 24 h. The films on copper were characterized by scanning electron microscopy, contact angle tests, and Fourier transform infrared spectroscopy. Molecular simulations provided the adsorption model of OP molecules on the Cu (111) surface.

Tumor necrosis factor superfamily 15 (TNFSF15) suppresses angiogenesis by specifically inducing apoptosis in proliferating endothelial cells. Death receptor 3 (DR3), a member of the TNF receptor superfamily (TNFRSF25), has been identified as a receptor for TNFSF15 to activate T cells. It is unclear, however, whether DR3 mediates TNFSF15 activity on endothelial cells. Here we show that siRNA-mediated knockdown of DR3 in an in vivo Matrigel angiogenesis assay, or in adult bovine aortic endothelial (ABAE) cell cultures, leads to resistance of endothelial cells to TNFSF15-induced apoptosis. Interestingly, DR3-depleted cells also exhibited markedly diminished responsiveness to TNFα cytotoxicity, even though DR3 is not a receptor for TNFα. Treatment of the cells with either TNFSF15 siRNA or a TNFSF15-neutralizing antibody, 4-3H, also results in a significant inhibition of TNFα-induced apoptosis. Mechanistically, DR3 siRNA treatment gives rise to an increase of ERK1/2 MAPK activity, and up-regulation of the anti-apoptotic proteins c-FLIP and Bcl-2, thus strengthening apoptosis-resisting potential in the cells. These findings indicate that DR3 mediates TNFSF15-induced endothelial cell apoptosis, and that up-regulation of TNFSF15 expression stimulated by TNFα is partly but significantly responsible for TNFα-induced apoptosis in endothelial cells.

Objective This study was conducted to understand the trends and research hotspots of clinical nursing in China and abroad, thereby to provide guidance for nursing practice and studies. Methods We retrieved clinical nursing literature (excluding literature related to psychological nursing and traditional Chinese medicine nursing) cited in Wanfang Data ( www.wanfangdata.com.cn ) and PubMed between 2007 and 2015 and subsequently performed bibliometric analyses on article volume, journal, clustering of high-frequency keywords, and co-occurrence of keywords. Results A total of 10374 publications, excluding those related to psychological nursing, were retrieved via a PubMed search. The literature displayed a rising trend in terms of annual publication volume. The journal distribution of clinical nursing publications overall was consistent with Bradford's Law. The main contents of clinical nursing literature between 2007 and 2009 included: (1) studies on effects of the midwife and midwifery methods for natural childbirth; (2) studies on emergency nursing care; (3) studies on dementia care; (4) studies on bandage dressing in trauma nursing; and (5) studies on quality of life in cancer patients nursing. The main contents of clinical nursing literature between 2010 and 2012 included: (1) studies on obstetric nurse–patient relationships; (2) studies on patients' medical team in stroke nursing; (3) studies on cancer nursing methods; (4) studies on nursing patients with trauma related to urinary incontinence; and (5) studies on the quality of life of caregivers of dementia patients. The main contents of clinical nursing literature between 2013 and 2015 included (1) studies on skin care and bandaging in trauma nursing; (2) studies on evidence-based nursing in AIDS care; (3) studies on nurses' role in obstetric nurse–patient relationships; studies on cancer nursing methods; (4) studies on nursing for Alzheimer's disease and dementia; and (5) studies on caregivers and nursing of stroke patients. A Wanfang Data search retrieved a total of 85570 publications, whose volume also exhibited an annual rising trend, in particular with regard to those in core journals. However, percentage of total publication volume, mean cited frequency per article, and total ranking of clinical nursing publications overall displayed a decreasing trend. The main contents of clinical nursing literature between 2007 and 2009 included: (1) diabetes nursing; (2) nursing for cancer; (3) nursing for senility-related diseases; (4) nursing in the event of complications; (5) nursing for hypertension; (6) studies on quality of life after nursing interventions; (7) chemotherapy nursing; (8) studies on compliance after nursing interventions; (9) constipation nursing; and (10) nursing for stroke patients. The main contents of clinical nursing literature between 2010 and 2012 included: (1) diabetes nursing; (2) nursing for cancer; (3) nursing for senility-related diseases; (4) studies on quality of life after nursing interventions; (5) nursing in the event of complications; (6) nursing for hypertension; (7) prevention nursing; (8) perioperative nursing; (9) pain nursing; and (10) studies on compliance after nursing interventions. The main contents of clinical nursing literature between 2013 and 2015 included: (1) diabetes nursing; (2) nursing in the event of complications; (3) cancer nursing; (4) studies on quality of life after nursing interventions; (5) nursing for stroke patients; (6) nursing for the elderly; (7) studies on compliance after nursing interventions; (8) nursing for hypertension; (9) constipation nursing; and (10) prevention nursing. Conclusions Clinical nursing research in China is in a rapid development stage as defined by Price's law whereby there is a rapid growth in publication volume. By comparison, clinical nursing research in developed countries is in the stable development stage or maturation phase, which is characterized by a flat curve of publication volume and stable development rate. There is a gap of 25–30 years between China and these countries in terms of the growth phases of clinical nursing literature.

This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms (PNENs). A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher's exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs (all P

Mouse bone marrow-derived Lin − -Sca-1 + endothelial progenitor cell (EPC) has pluripotent abilities such as supporting neovascularization. Vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) (Flt1) recognizes various VEGF isoforms and is critically implicated in a wide range of physiological and pathological settings, including vasculogenesis. Mouse EPC expresses two isoforms of VEGFR1: mFlt1, which transmits ligand-induced signals; and sFlt1, which acts as a negative regulator by sequestering ligands of VEGF receptors. How the relative levels of mFlt1 and sFlt1 are regulated is not yet clear. We report here that tumor necrosis factor superfamily 15 (TNFSF15) (also known as VEGI or TL1A), an endothelial cell-secreted cytokine, simultaneously promotes mFlt1 degradation and up-regulates sFlt1 expression in EPC, giving rise to disruption of VEGF- or PlGF-induced activation of eNOS and MAPK p38 and effective inhibition of VEGF-driven, EPC-supported vasculogenesis in a murine Matrigel implant model. TNFSF15 treatment of EPC cultures facilitates Akt deactivation-dependent, ubiquitin-assisted degradation of mFlt1 and stimulates sFlt1 expression by activating the PKC, Src, and Erk1/2 signaling pathway. Additionally, TNFSF15 promotes alternative splicing of the Flt1 gene in favor of sFlt1 production by down-regulating nuclear protein Jumonji domain-containing protein 6 (Jmjd6), thus alleviating Jmjd6-inhibited sFlt1 expression. These findings indicate that TNFSF15 is a key component of a molecular mechanism that negatively modulates EPC-supported vasculogenesis through regulation of the relative levels of mFlt1 and sFlt1 in EPC.

The waste water containing dyes is difficult to be biochemically treated because of its deep color. Adsorption becomes an important treatment method for this kind of waste water. The iron organic framework was rapidly synthesized at room temperature, and characterized by IR and XRD. Adsorption properties of the materials were tested using four anonic dyes solutions. It was found that the iron organic framework could be formed rapidly, with higher surface area and pore volumes. The pH value of zero point charge was 3.7. The adsorption experiments showed that the iron organic material could remove more dyes in acid solution. The dye adsorption capacity increased with increasing dye concentration. These adsorption data fitted well with Langmuir thermoadsorption equation. The calculated parameter from Langmuir adsorption indicated that the adsorption process could be performed easily. The second order kinetic equation could describe the adsorption data. In addition, the structure of dyes could affect the adsorption process. The metal complex dyes could be quickly removed.

Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change—mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo.

In this paper, we propose a new method to realize quick update of information concerned with shared contents in Peer-to-Peer (P2P) networks. The proposed method is a combination of a hierarchical P2P architecture and a tag-based file management scheme. The hierarchical architecture consists of three layers: the top layer consisting of a collection of central servers, the middle layer consisting of a set of sub-servers, and the bottom layer consisting of a number of user peers. Indexes of files held by each user peer are stored at the sub-servers in the middle layer, and the correlation between file indexes and sub-servers is maintained by central servers using tags. We implemented a prototype of the proposed method using Java, and evaluated the performance through simulations using PeerSim 1.0.4. The results of our experiments indicate that the proposed method is a good candidate for “real-time search engines” in P2P systems; e.g., it completes an upload of 10, 000 file indexes to the relevant sub-servers in a few minutes and achieves query forwarding to relevant peers within 100ms.

2,5-Dimercapto-1,3,4-thiadiazole (DMTD) monolayer was self-assembled on the fresh copper surface to form protective monolayer against copper corrosion in acidic solution. Its corrosion inhibition was investigated in 0.5 M HCl by cyclic voltammetry, potentiodynamic polarization and electrochemical impedance spectroscopy methods. The results revealed that the DMTD monolayer inhibited the copper corrosion effectively with the optimum self-assembly time of 10 h and the optimum self-assembly concentration of 7.5 mM. Surface observation was performed using scanning electron microscope, contact angle goniometer and Fourier transform infrared spectrometer. The molecular simulation has been used to simulate the adsorption model of DMTD molecule on Cu(1 1 1) surface.

Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor-C/D (VEGF-C/D) and VEGF receptor-3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF-C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium-derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up-regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain-containing receptor-3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15-DR3 interaction with a Tnfsf15 neutralizing antibody, 4-3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF-κB. Tnfsf15-overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild-type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4-3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up-regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema.

In this paper, the authors address the issue of automatic tag attachment to the documents distributed over a P2P network aiming at improving the efficiency of file search in such networks. The proposed scheme combines text clustering with a modified tag extraction algorithm, and is executed in a fully distributed manner. Meanwhile, the optimal cluster number can also be fixed automatically through a distance cost function. We have conducted experiments to evaluate the accuracy of the proposed scheme. The result of experiments indicates that the proposed approach is capable of making effective and efficient tag attachment in real scenarios; i.e., for more than 90% of documents, it attaches the same tags as the ones attached by human reviewers. Moreover, it proofs by the experiments that the optimal cluster number is almost the same as the number of topics from the website.

In this paper, we consider the problem of automatic tag attachment to the documents distributed over a P2P network aiming at improving the efficiency of file search in such networks. The proposed scheme combines text clustering with a modified tag extraction algorithm, and is executed in a fully distributed manner. We conducted experiments to evaluate the accuracy of the proposed scheme. The result of experiments indicates that for more than 90% of documents, it attaches the same tags as the ones attached by human reviewers.

SET and MYND domain-containing protein 3 (SMYD3) is a novel histone methyltransferase involved in human carcinogenesis. To further establish the transgenic mice of SMYD3 and provide a useful platform for the study of SMYD3 and the screening of novel antitumor drugs, a transgene for liver-specific simultaneous expression of SMYD3 and EGFP was constructed. The human SMYD3 gene was subcloned into pIRES2-EGFP eukaryotic expressing vector. Subsequently, mice albumin promoter (pALB) (−821∼+59) was obtained from the mice genome DNA by PCR and then inserted into the 5' flanking region of SMYD3. The final recombinant plasmid (named as pIRAS) was digested by AflII StuI and XhoI , and the DNA fragment consisting of albumin promoter (pALB) SMYD3 Internal Ribosome Entry Site (IRES) Enhanced Green Fluorescent Protein (EGFP) and SV40 polyA signal sequence (named as ASIES) was released. The linearized, purified ASIES transgene was microinjected into C57BL/6 mouse zygotes. After cultured for 2 days in vitro, most of the injected zygotes showed normal division, and the following works would establish the transgenic mice.