RANKL-induced M1 macrophages are involved in bone formation

The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide(LPS) and interferon-γ(IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages(BMDMs) were activated with LPS+IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction(RT-q PCR) and fluorescence-activated cell sorting(FACS). Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive(iNOS+) cells in vivo, suggesting an association between RANKL expression and i NOS+ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger M1-like macrophages with properties that were different from those of LPS+IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.

Selection Model of Optional Parts in Suppliers Involved in New Product Development

Quality function deployment (QFD),which can translate efficiently customer requirement (CRs) into technical attributes (TAs),is widely used in new product development (NPD) as an efficient customer-driven approach. After lots of QFD application is applied in manufacturing fields,it was proved that without considering suppliers involved,it is difficult to get precise and satisfying results in each process of QFD,particularly part deployment. The paper will address the issues of a model of optional parts selection in suppliers involved in part deployment process. Further,it has been applied to an ERP system reconstruction and updating problem as an illustration.

Cyclin L2, a novel RNA polymerase Ⅱ-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells

We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.

Short-term outcomes after the loading phase of intravitreal bevacizumab and subthreshold macular laser in non-center involved diabetic macular edema

AIM: To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation(SMP), for the treatment of non-center involved diabetic macular edema(non-CI DME).METHODS: Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity(BCVA) of 0.30 logMAR or better. Each eye was randomized into three groups:group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness(CST), macular area of greater thickness(MAGT) and total macular volume(TMV). Results were analyzed after 3 mo.RESULTS: A total of 32 eyes were included. Group 3 improved in BCVA(0.19±0.16 to 0.12±0.14 logMAR; P=0.041) and in TMV(7.90±0.57 to 7.65±0.73 mm3; P=0.025). Group 1 improved in MAGT(325±26.26 to 298.20±44.85 μm; P=0.022) and TMV(7.79±0.57 to 7.50±0.56 mm3, P=0.047). Group 2 didn't show significant improvement of any variable.CONCLUSION: The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.

GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization,mitochondria-targeting and-activating properties of human salivary histatin 1

Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular mechanism.However,its regulating signaling pathways remain to be elucidated.We investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of F-Hst1.We performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of Hst1.We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1.Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1.The inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity.Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1.We further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important role.Overall,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular targeting.The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.

Molecular Cloning and Characterization of Genes Involved in Cotton(Gossypium barbadense L.) Response to Verticillium dahliae

Verticillium dahliae Kleb.is a necrotrophic plant pathogen which causes serious soil borne vascular disease in cotton.The molecular basis the defense response of cotton to this pathogen is

The Perception of Health Workers and Stakeholders Involved in the Process of Selecting Indigent in Burkina Faso

Background: Indigent selected for their health care is complex and poses enormous challenges. The actors involved have an influence on health actions and their perception is decisive for better care for the indigent. Little evidence exists on these perceptions and this paper has captured this. Methods: A case study involved 163 participants with a questionnaire and an interview guide. The quantitative responses were classified according to a measurement scale, proportions and overall indices of perception (Ip) and satisfaction (CSAT) were calculated. The relationship between variables was investigated using chi-square. Thematic analysis was used with qualitative data. The study met ethical requirements. Results: The participants had a positive perception of the selection: Ip = 0.77, but a minority (1/5) were dissatisfied with the selection. The perception of selection did not differ significantly depending on the experience of the actors. For the vast majority, the definition of indigent was satisfactory (CSAT = 91.4). The selection was done in a top down fashion and steps such as setting up committees, informing stakeholders, had shortcomings which negatively impacted the effectiveness of the selection. The needs of the participants included transparency in the indigent select process, matching the tools for selecting the indigent to the context, strengthening of local action, deconstruction of prejudices in terms of the indigent, power of actors to act, and importance for health services to reach out to the indigent. Conclusion: Considering the perception of the actors as well as their needs will improve the selection for effective care of the indigent.

Identification and analysis of differentially expressed genes involved in dark-induced photoperiod response and senescence of soybean leaves by suppression subtractive hybridization

A cDNA subtractive library enriched for dark-induced up-regulated ESTs was constructed by suppression subtractive hybridization(SSH) from leaf tissues of soybean cultivar DongNong L13 treated with short-day(8-h light/16-h dark) and long-day(16-h light/8-h dark) conditions.A total of 148 clones were sequenced,representing 76 unique ESTs which corresponded to about 20% of 738 clones from the cDNA library and showed a significant up-regulation of at least three fold verified by dot blot hybridization.The putative functions of ESTs were predicted by Blastn and Blastx.The 43 differentially expressed genes identified by subtractions were classified according to their putative functions generated by Blast analysis.Genetic functional analysis indicated that putative proteins encoded by these genes were related to diverse functions during organism development,which include biological regulation pathways such as transcription,signal transduction and programmed cell death,protein,nucleic acid and carbohydrate macromolecule degradation,the cell wall modification,primary and secondary metabolism and stress response.Two soybean transcription factors enhanced in SD conditions,GAMYB-binding protein and DNA binding protein RAV cDNAs that may be involved in SD soybean photoperiod response,had been isolated using 5'-and 3'-rapid amplification of cDNA ends(RACE)(Genbank Accession numbers DQ112540 and DQ147914).

The Prognostic Value of Minimally Involved Melanoma Sentinel Lymph Nodes

Background: Sentinel node (SLN) status is the most important prognostic factor for early-stage melanoma patients. It will influence follow-up and may change therapy. Positive SLNs present different degrees of involvement so that subgroups of patients may have minimal SLN invasion. The aim of this study was to evaluate survival in subgroups with minimally involved SLNs and to compare them to negative SLN patients. Method: SLN biopsy was performed in 499 consecutive clinically N0 patients between 1997 and 2008. Following updated recommendations from the Melanoma Group of the European Organization of Research and Treatment of Cancer, degrees of SLN involvement were fully reassessed for two anatomopathological parameters: tumour burden according to Rotterdam criteria (1.0 mm) and microanatomic location according to Dewar (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive). Minimally involved SLNs were defined as those with tumor burden <0.1 mm and/or subcapsular metastasis location. Kaplan-Meier and multivariable logistic regression analyses were performed. Results: Out of 499 clinically N0 patients, positive SLNs were found in 123 patients (24.7 percent). With a median follow-up of 52 months (range: 9 - 146), five-year disease-free (DFS), disease-specific survival (DSS) and overall survival (OS) were 88.1, 93.9 and 89.9 percent for negative SLN patients, respectively. In minimally involved SLNs, there were 21 with tumour burden <0.1 mm, and 52 with subcapsular metastasis. Five-year DFS, DSS and OS in these sub-groups were 79.6, 86.6 and 86.6 percent, then 57.3, 69.8 and 67.8 percent respectively. DFS univariable analysis of these sub-groups compared to negative SLNs showed: (HR1.89, 95 percent CI 0.75 - 4.79;p 0.175) and (HR 3.92, 95 percent CI 2.29 - 6.71;p < 0.0001) respectively. Minimally involved sub-groups were not predictive for NSLN negativity. Conclusion: Rotterdam’s tumour burden stratification is an easy and useful prognostic factor of melanoma survival. There was a trend showing that patients with SLN tumour burden <0.1 mm have a lower survival compared to SLN negative patients. One might suggest that patients with minimally involved SLNs may not be managed similarly to negative SLN patients. Subcapsular metastasis subgroup according to the microanatomic location has statistically significant worst survival.

Expression Profile Analysis of Genes Involved in Brassinosteroid Biosynthesis Pathway in Cotton Fiber Development

Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear

China Allows Foreigners to Become Involved in Property Business

China had a developed property market in the 1980s. The property business has brought considerable returns to the national economy and become an important way of optimizing the distribution of state-owned property in the socialist market economy for the past decade or so. Since 1991, the property markets in Tianjin, Shanghai, Wuhan, Shenzhen and 12 other cities

3-73 Both p21 and Cytoskeleton are Involved in Radiation Induced Cell Cycle Arrest in Uveal Melanoma 92-1 Cells

One of the main engines that drive cellular transformation is the loss of proper control of the cell cycle. Thecyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response tomany stimuli[1]. Our recent study[2;3] showed that a global and stable cell cycle block was established in 92-1 cellsafter 10 Gy of X-ray and carbon ion irradiation and cells underwent senescence 5 d later. p21 was detected at highlevels from 4 h to 5 d after irradiation in these cells, which implied that p21 played a crucial role in cellular responseto irradiation.

More Young Experts to Be Involved in IEC Work

The first national action for IEC Young Professional Program was started with a pilot activity held in Shenzhen of south China from July 3 to 6,2017,which attracted the domestic young experts from leading enterprises and research institutes such as Huawei,ZTE,BYD and Kuang-Chi.The event invited top-level international standardization experts to give lectures and set up the

BH3-only protein Bim is involved in myocardial injury induced by co-stress of ischemia and cold stress in rats

Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left coronary artery.SD rats were randomly allocated to 4 groups; sham+normal temperature(S group),sham+cold stress(SC group),myocardial ischemia+ normal temperature(Ⅰgroup), myocardial ischemia+cold stress(IC group).On the condition of 26℃,SC and IC groups were keeped in a 4℃artificial chamber for 8h(8;00-16:00) for 4 consecu- tive days.Car diac function was assessed by echocardiography;pathological change was analyzed by HE staining;myocardial infarct size was determined by TTC staining;Bim,Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly make the cardiac muscle in abnormal shape,increase the infarct size and the expression of Bim and Caspase-3.Conclusions Co-exposure of myocardial ischemia and cold stress may aggravate the cardiac injury,pro- apoptosis protein Bim is involved.

JKR Involved in Developing Old Oilfields in Jilin

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Chinese Enterprises Involved in Overseas Research

While a large batch of overseas companies have established research instiutions in China, a group of Chinese brand name enterprises have also established research institutions in other countries, and some Chinese enterprises even "take away" talents from foreign corporations, living them with high salaries.

NPC Deputies More Actively Involved in Politics

Putting forward bills and proposals is the right of people’s deputies endowed by law and the Constitution and one of the important ways for them to participate in the management of state affairs on behalf of the people. It is also one of the major channels to voice the popular feelings and wills. With the deepening of democracy and legal construction in recent years, people’s deputies have become more conscious of participating in state manage-

First Tibetan Policeman Involved in International Peacekeeping Mission

Dainzin, 39 this year, is a policeman in Lhasa. Twice in 2000 and 2002 respectively, he was sent by the PRC Ministry of Public Security to work for UN peacekeeping mission in East Timor, thus becoming the first Tibetan policeman involved in the international mission. His good behavior won his a medal from the United Nations and a medal from the police authorities of East Timor.

Statistical models for predicting number of involved nodes in breast cancer patients

Clinicians need to predict the number of involved nodes in breast cancer patients in order to ascertain severity, prognosis, and design subsequent treatment. The distribution of involved nodes often displays over-dispersion—a larger variability than expected. Until now, the negative binomial model has been used to describe this distribution assuming that over-dispersion is only due to unobserved heterogeneity. The distribution of involved nodes contains a large proportion of excess zeros (negative nodes), which can lead to over-dispersion. In this situation, alternative models may better account for over-dispersion due to excess zeros. This study examines data from 1152 patients who underwent axillary dissections in a tertiary hospital in India during January 1993-January 2005. We fit and compare various count models to test model abilities to predict the number of involved nodes. We also argue for using zero inflated models in such populations where all the excess zeros come from those who have at some risk of the outcome of interest. The negative binomial regression model fits the data better than the Poisson, zero hurdle/inflated Poisson regression models. However, zero hurdle/inflated negative binomial regression models predicted the number of involved nodes much more accurately than the negative binomial model. This suggests that the number of involved nodes displays excess variability not only due to unobserved heterogeneity but also due to excess negative nodes in the data set. In this analysis, only skin changes and primary site were associated with negative nodes whereas parity, skin changes, primary site and size of tumor were associated with a greater number of involved nodes. In case of near equal performances, the zero inflated negative binomial model should be preferred over the hurdle model in describing the nodal frequency because it provides an estimate of negative nodes that are at “high-risk” of nodal involvement.