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This article aims to explore the trends of monoclonal antibodies (mAbs) research and commercialization, mainly to examine the development trajectories by a contrastive exploration of successful and unsuccessful mAb. This work is based on two sets of R&D project reports, consisting of 517 discontinued mAb project reports and 64 marketed mAb project reports, from IMS Lifecycle R&D Focus. The analysis of drug development processes will provide the basic evidences of mAb technology commercialization. We examined the mAb research and commercialization from three perspectives: (1) Countries with mAb research activity; (2) Organizations participating in mAb research and development; and (3) Clusters of keywords (indication and class description) regarding mAb. The technology factor, the market factor and the abilities of participating firms to pursue commercialization were analyzed. Through data analysis, we have discovered that the research and development on mAb has reached a mature and diversified stage.

Background Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. Material/Methods A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. Results A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074–1.894), P=0.014), rectal cancer (OR=1.483(1.102–1.996), P=0.009), and TRG 1–2 vs. 3–5 group (OR=1.423(1.046–1.936), P=0.025), while other polymorphism including MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms exerted significant association under all genetic models in overall analysis or subgroup analysis. Conclusions MTHFR C677T might be correlated with the tumor response to pRCT. Further well-designed, larger-scale epidemiological studies are needed to validate our results.

In this study, the tetrad stage of microspore development in a new cotton (Gossypium barbadense L.) cytoplasmic male sterility (CMS) line, H276A, was identified using paraffin sections at the abortion stage. To explore the molecular mechanism underlying CMS in cotton, a comparative transcriptome analysis between the CMS line H276A and its maintainer line H276B at the tetrad stage was conducted using an Illumina HiSeq 4000 platform. The comparison of H276A with H276B revealed a total of 64,675 genes, which consisted of 59,255 known and 5420 novel genes. An analysis of the two libraries with a given threshold yielded a total of 3603 differentially expressed genes (DEGs), which included 1363 up- and 2240 down-regulated genes. Gene Ontology (GO) annotation showed that 2171 DEGs were distributed into 38 categories, and a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 2683 DEGs were classified into 127 groups. Thirteen DEGs were randomly selected and detected by quantitative reverse-transcribed PCR (qRT-PCR), and the results indicated that the transcriptome sequencing results were reliable. The bioinformatic analysis results in conjunction with previously reported data revealed key DEGs that might be associated with the male sterility features of H276A. Our results provide a comprehensive foundation for understanding anther development and will accelerate the study of the molecular mechanisms of CMS in cotton.

The hypothalamic-pituitary-gonadal (HPG) axis plays a critical role in regulating reproductive function. Gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus, acts on pituitary gonadotrophs to stimulate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and secretion, ultimately affecting the animal's fertility. MicroRNAs are small, non-coding RNAs that are widely expressed throughout the brain and can fine-tune gene expression post-transcriptionally. Recently, growing evidence has unveiled the central position of miRNAs within a key regulatory process involving GnRH secretion and subsequent activation in the pituitary. Although transcriptional regulation of reproduction has been well studied, the post-transcriptional processes are less well understood. In this review, we elaborate comprehensively on the critical role of miRNAs in the reproductive process, including both temporal and spatial aspects. A better understanding of how miRNAs impact the neuroendocrine system may improve our knowledge of reproduction and provide novel targets for therapeutic development.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that results in the production of dysfunctional pollen. Based on reliable reference gene-normalized real-time quantitative PCR (RT-qPCR) data, examining gene expression profile can provide valuable information on the molecular mechanism of kenaf CMS. However, studies have not been conducted regarding selection of reference genes for normalizing RT-qPCR data in the CMS and maintainer lines of kenaf crop. Therefore, we studied 10 candidate reference genes (ACT3, ELF1A, G6PD, PEPKR1, TUB, TUA, CYP, GAPDH, H3, and 18S) to assess their expression stability at three stages of pollen development in CMS line 722A and maintainer line 722B of kenaf. Five computational statistical approaches (GeNorm, NormFinder, ΔCt, BestKeeper, and RefFinder) were used to evaluate the expression stability levels of these genes. According to RefFinder and GeNorm, the combination of TUB, CYP, and PEPKR1 was identified as an internal control for the accurate normalization across all sample set, which was further confirmed by validating the expression of HcPDIL5-2a. Furthermore, the combination of TUB, CYP, and PEPKR1 was used to differentiate the expression pattern of five mitochondria F1F0-ATPase subunit genes (atp1, atp4, atp6, atp8, and atp9) by RT-qPCR during pollen development in CMS line 722A and maintainer line 722B. We found that atp1, atp6, and atp9 exhibited significantly different expression patterns during pollen development in line 722A compared with line 722B. This is the first systematic study of reference genes selection for CMS and will provide useful information for future research on the gene expressions and molecular mechanisms underlying CMS in kenaf.

We investigated the evolution process of collaborative inter-organizational network of the research and development (R&D) on monoclonal antibody (mAb) over the past 30 y. The annual detection of the collaboration network provides dynamics on network structures and relationship changes among different organizations. Our research showed continuous growth of the network's scale and complexity due to the constant entry of new organizations and the forging of new partnering relationships. The evolving topological features reveal a core-periphery structure that became clearer over time and an increasing heterogeneity within the collaborative mAb R&D network. As measured by the number of network participants, dedicated biotechnology firms (DBFs) were the dominant organization form in the field of mAb development, but their average centrality was reduced during the period of 2004–2009, when pharmaceutical companies took over the positions of DBFs. Along with the network evolution, 2 waves of substitution on the leading positions were driven by technological innovations and mergers and acquisitions (M&A). In addition, this study analyzed organizational-level behaviors to help understand the evolution of network structures over the field of mAb development across the different technologically innovative or economic contexts.

Having more information on yeast ecology during fermentation process is important for producing wine with typical characteristics. Till now, it is unclear how agricultural practices of grape influence yeast succession and wine quality. In this study, high-throughput sequencing was implemented to study yeast succession during spontaneous fermentation of grapes from both organic and conventional agricultural systems. Basic physicochemical parameters and sensory quality of wine samples were also examined. Results showed a total of 18 yeast genera (including 36 species) were identified, and these two kinds of samples differed a lot in yeast community compositions and succession. Hanseniaspora and Saccharomyces were the top two dominant genera, between which Hanseniaspora was superior at the beginning while the relative abundance of Saccharomyces boomed during fermentation and reached 99.96 ± 0.005% (organic) and 79.94 ± 7.76% (conventional) ultimately. Some species which were rare in vine and wine also emerged in this work. Yeast alpha diversity of organic sample fell more sharply than that of conventional sample during fermentation. Besides, organic sample had advantages in fermentation speed and wine sensory quality. This study enhanced our knowledge about yeast ecology during spontaneous fermentation of wine and demonstrated the influence of viticultural practices on yeast succession and wine quality.

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β–activated kinase-1 (TAK1) phosphorylation of NF-κB–activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB–mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

A characterization of orthodox transversals is given and the maximum idempotent-separating congruence concerned with quasi-ideal orthodox transversals is explored. The well-known results about orthodox semigroups are generalized and enriched.

Manipulation of planting density and choice of variety are effective management components in any cropping system that aims to enhance the balance between environmental resource availability and crop requirements. One-time fertilization at first flower with a medium plant stand under late sowing has not yet been attempted. To fill this knowledge gap, changes in leaf structural (stomatal density, stomatal length, stomata width, stomatal pore perimeter, and leaf thickness), leaf gas exchange, and chlorophyll fluorescence attributes of different cotton varieties were made in order to change the planting densities to improve lint yield under a new planting model. A two-year field evaluation was carried out on cotton varieties&mdash, V1 (Zhongmian-16) and V2 (J-4B)&mdash, to examine the effect of changing the planting density (D1, low, 3 &times, 104, D2, moderate, 6 &times, and D3, dense, 9 &times, 104) on cotton lint yield, leaf structure, chlorophyll fluorescence, and leaf gas exchange attribute responses. Across these varieties, J-4B had higher lint yield compared with Zhongmian-16 in both years. Plants at high density had depressed leaf structural traits, net photosynthetic rate, stomatal conductance, intercellular CO2 uptake, quenching (qP), actual quantum yield of photosystem II (&Phi, PSII), and maximum quantum yield of PSII (Fv/Fm) in both years. Crops at moderate density had improved leaf gas exchange traits, stomatal density, number of stomata, pore perimeter, length, and width, as well as increased qP, &Phi, PSII, and Fv/Fm compared with low- and high-density plants. Improvement in leaf structural and functional traits contributed to 15.9%&ndash, 10.7% and 12.3%&ndash, 10.5% more boll m&minus, 2, with 20.6%&ndash, 13.4% and 28.9%&ndash, 24.1% higher lint yield averaged across both years, respectively, under moderate planting density compared with low and high density. In conclusion, the data underscore the importance of proper agronomic methods for cotton production, and that J-4B and Zhongmian-16 varieties, grown under moderate and lower densities, could be a promising option based on improved lint yield in subtropical regions.

Cytoplasmic male sterility (CMS) is an important agronomic feature and provides an effective tool for heterosis utilization of crops. This study reports the comparative transcriptomic sketches between a novel allohexaploid cotton progeny CMS line LD6A and its maintainer line LD6B using de novo transcriptome sequencing technology at the pollen abortion stage. A total of 128,901 Unigenes were identified, in which 2007 were upregulated and 11,864 were downregulated. The significantly differentially expressed genes (DEGs) in LD6A show a distant and diverse genetic nature due to their distant hybrid hexaploidy progeny. Further analysis revealed that most of the DEGs participated in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, histone acetyltransferase activity, sepal development, stigma development, cotyledon development and microsporogenesis. A highly differentially expressed toxic protein, Abrin, was identified in the CMS line LD6A, which can catalyze the inactivation of ribosomes and consequently lead to cell death through the mitochondrial pathway in human cells. Twelve DEGs were selected randomly to validate transcriptome data using quantitative reverse-transcribed PCR (qRT-PCR). This study will contribute to new ideas and foundations related to the molecular mechanism of CMS and the innovation of cotton germplasm resources.

Cationic asphalt emulsifier needs to adjust the system to acidity during use, which will bring potential corrosion hazard to emulsified asphalt production equipment. In this paper, a bifunctional asphalt emulsifier with emulsification and corrosion inhibition was synthesized. The results show that the bifunctional cationic asphalt emulsifier has excellent surface activity, the critical micelle concentration is 56.23 μg/g, and the surface tension value is 25.79 mN/m, the prepared emulsified asphalt has good stability, and the stability of 1d and 5d are 0.28 % and 0.97 %, respectively. At the same time, the asphalt emulsifier has good corrosion inhibition performance for different material test pieces and different corrosive environments. The mechanism study shows that the emulsifier forms a dense adsorption protective film on the metal surface, so that the metal surface in the acid environment is protected from corrosion and the corrosion rate is lowered.

In this study, the atp8 gene was cloned from the cytoplasmic male sterile (CMS) line UG93A and its maintainer line UG93B in kenaf. Its DNA sequence analysis showed that atp8 containing 480-bp, encoding 159 amino acid residues, and a 9-bp insertion was found at the 3′flanking sequence in UG93A compared with UG93B. The cDNA sequence of atp8 analyzed by RT-PCR indicated that there were five loci edited, but six loci edited in UG93B. The editing frequencies were higher in sterile cytoplasm than in fertile cytoplasm. The relative expression of atp8 analyzed by real-time PCR showed that the expressed level of atp8 in UG93A was lower than that of its maitainer UG93B and its F1 hybrid UG93A/992 (a restore line). Furthermore, based on the difference of the 9-bp differences at the 3′flanking sequence of atp8 between UG93A and UG93B, a molecular marker specific to male sterile cytoplasm was developed, which can be used for indentifying whether any germplasm of kenaf is male sterile cytoplasm or male fertile cytoplasm.

Introduction: Inhibitors of programmed cell death 1 (PD-1) and its ligands are producing a paradigm shift in cancer treatment. The promising clinical outcomes and a multi-billion dollar market have prompted active research and development and resulted in relentless patent protection. However, the global patent landscape in this field remains unclear. Areas covered: The patent landscape encompassing global patenting activities and developing trends in the field is discussed based on a data set of 1287 patent families. Patenting activities have expanded rapidly in the past three years. Specific trends in relevant aspects are presented, including patent filing countries, patent ownership, co-patents, technical areas, and technological connections in terms of patent citation relationships. Expert opinion: Together with patenting momentum in recent years, fragmented ownership and dense technological connections of PD-1-related inventions raise the possibility of a patent thicket. The explosion of patent applications and complex citation relationships could also lead to considerable patent conflicts and disputes on overlapping intellectual property rights, in addition to existing legal uncertainties. Patent applicants in this field are encouraged to be aware of these concerns when developing valid patent strategies.

In this paper, another relationship between the quasi-ideal adequate transversals of an abundant semigroup is given. We introduce the concept of a weakly multiplicative adequate transversal and the classic result that an adequate transversal is multiplicative if and only if it is weakly multiplicative and a quasi-ideal is obtained. Also, we give two equivalent conditions for an adequate transversal to be weakly multiplicative. We then consider the case when I and Λ (defined below) are bands. This is analogous to the inverse transversal if the regularity condition is adjoined.

Left simplistic orthodox transversals are introduced in this paper and some characterizations as-sociated with them are obtained. The related results of Blyth and Almeida Santos on left simplistic inverse transversals obtained in 1996 and Kong on orthodox transversals obtained in 2007 are generalized and ampli ed. A structure theorem of regular semigroups with left simplistic orthodox transversals is also established.

Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ERα-positive breast cancer. Many underlying molecular events that confer resistance are known but a unifying theme is yet to be revealed. In this report, we provide evidence that HOXB7 overexpression renders MCF-7 cells resistant to tamoxifen via cross-talk between receptor tyrosine kinases and ERα signaling. HOXB7 is an ERα-responsive gene. Extended treatment of MCF-7 cells with tamoxifen resulted in progressively increasing levels of HOXB7 expression, along with EGFR and EGFR ligands. Up-regulation of EGFR occurs through direct binding of HOXB7 to the EGFR promoter, enhancing transcriptional activity. Finally, higher expression levels of HOXB7 in the tumor significantly correlated with poorer disease-free survival in ERα-positive patients with breast cancer on adjuvant tamoxifen monotherapy. These studies suggest that HOXB7 acts as a key regulator, orchestrating a major group of target molecules in the oncogenic hierarchy. Functional antagonism of HOXB7 could circumvent tamoxifen resistance.

An inverse transversal of a regular semigroup S is an inverse subsemigroup that contains precisely one inverse of each element of S. This concept was first introduced by Blyth and McFadden and generalized to an adequate transversal in the abundant case by El-Qallali. In this paper we show that the product of any two quasi-ideal adequate transversals of an abundant semigroup S which satisfy the regularity condition is a quasi-ideal adequate transversal of S. Furthermore, all adequate transversals of S form a rectangular band.

A new kind of amino acid descriptors we named integrated property scores (IP scores), were derived from 516 physico‐chemical properties using the classical principal component analysis technique, and employed to characterise the sequence pattern profile of 162 single-protonated tripeptides. Based upon the sophisticated partial least squares (PLS) regression coupled with genetic algorithm-variable selection, the resulting structural parameters of the characterisation were then used to develop several robust quantitative structure–spectrum relationship models with the ion mobility spectrometry collision cross sections of these peptides. The results for 94.1% samples in the data panel are satisfactorily accurate, compared to those experimentally measured. Subsequently, the predictive power and stability of the constructed models were analysed and tested in detail through both internal and external validations, with the correlation coefficients of fitting r 2, cross-validation q 2 and prediction of 0.978, 0.9...

Water plays an invaluable role in governing the structure, stability, dynamics, and function of biomolecules, which has also been demonstrated to be critical in mediating biomolecular recognition and association. Accurate determination of the dynamic behavior of water molecules at biological complex interface is important for the understanding of the molecular mechanism of water contributing to the binding between biomolecules and could be exploited as an alternative tool to refine the water's positions in X-ray electron density map. In the present study, a method called local hydrophobic descriptors (LHDs) is used to characterize the hydrophobic landscapes of the hydration sites at protein-DNA interface. The resulting variables of the characterization are then correlated with the experimentally measured B-factor values of 4445 elaborately selected water samples derived from a panel of thematically nonredundant, high-quality protein-DNA interfaces by using a variety of machine learning methods, including PLS, BPNN, SVM, LSSVM, RF, and GP. The results show that the dynamic behavior of interfacial water molecules is primarily governed by the local hydrophobic feature of the hydration sites that water molecules located, and the nonlinear dependence dominates over the linear component in the water B-factor system. We expect that this structured-based approach can be used for predicting the B-factor profile of other biomolecules as well.

In this paper, the connection of the inverse transversal with the adequate transversal is explored. It is proved that if S is an abundant semigroup with an adequate transversal , then S is regular if and only if is an inverse semigroup. It is also shown that adequate transversals of a regular semigroup are just its inverse transversals. By means of a quasi-adequate semigroup and a right normal band, we construct an abundant semigroup containing a quasi-ideal S-adequate transversal and conversely, every such a semigroup can be constructed in this manner. It is simpler than the construction of Guo and Shum [9] through an SQ-system and the construction of El-Qallali [5] by W(E, S).

In any abundant semigroup with a quasi-adequate transversal, we de ne two sets R and L and give some properties and characterizations associated with them. Then we give a structure theorem for abundant semigroups with multiplicative quasi-adequate transversals by means of two quasi-adequate semigroups R and L.

The functional role of autocrine trefoil factor-1 (TFF1) in mammary carcinoma has not been previously elucidated. Herein, we demonstrate that forced expression of TFF1 in mammary carcinoma cells resulted in increased total cell number as a consequence of increased cell proliferation and survival. Forced expression of TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology with increased cell migration and invasion. Moreover, forced expression of TFF1 increased tumor size in xenograft models. Conversely, RNA interference-mediated depletion of TFF1 in mammary carcinoma cells significantly reduced anchorage-independent growth and migration. Furthermore, neutralization of secreted TFF1 protein by polyclonal antibody decreased mammary carcinoma cell viability in vitro and resulted in regression of mammary carcinoma xenografts. We have therefore demonstrated that TFF1 possesses oncogenic functions in mammary carcinoma cells. Functional antagonism of TFF1 can therefore be considered as a novel therapeutic strategy for mammary carcinoma.

In any regular semigroup with an orthodox transversal, we define two sets R and L using Green’s relations and give necessary and sufficient conditions for them to be subsemigroups. By using R and L, some equivalent conditions for an orthodox transversal to be a quasi-ideal are obtained. Finally, we give a structure theorem for regular semigroups with quasi-ideal orthodox transversals by two orthodox semigroups R and L.

Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage-independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma.

Two kinds of multi-amine imidazoline E1 and E2 are synthetized as asphalt emulsifier by the long-chain organic acids and polyethylene polyamine. The purpose of adjusting the mixing time of asphalt emulsion and aggregate can be achieved by controlling the head group number of hydrophilic group. The re- search results show that the synthetic emulsifier with excellent surface performances; critical micelle concen- tration (CMC) of E1 and E2 are 0.0728 mmol.L -1 and 0.1508 mmol.L -1 under 25 ℃, respectively. The surface tension σcmc are 23.47 mN.m -1 and 28.50 mN.m -1 under the CMC. The addition of the head group of hydrophilic group makes the CMC and σcmc increase. The particles of asphalt emulsions prepared by two kinds of emulsi- fiers are uniform. The volume average particle size are respectively 2.56 μm and 2.33 μm. The increase of amidogen head group number of hydrophilic group is conducive to extend mixing time. the mixing time with the aggregate of the asphalt emulsion prepared by E1 and E2 are respectively 65s and 146s. KEYWORD: imidazoline, emulsifier, mixing time, surface activity.

We give some simple algebraic conditions on the coefficients of a boundary value problem for a differential equations of Ventcel type, depending on a spectral parameter, which guarantee the existence, uniqueness of a solution and coerciveness estimate, for a spectral parameter lying in some sector.

As the subject of active research and development (R&D) in recent decades, monoclonal antibodies have emerged among the major classes of therapeutic agents for treatment of many human diseases, especially cancers, infections, and immunological disorders. This article surveys the landscape of R&D projects of therapeutic monoclonal antibodies (mAbs), which are mostly used for disease immunotherapy, from a number of perspectives, including therapeutic indications, development phases, participants, and citation of related patents. The results of this research can be used as a reference resource for pharmaceutical researchers, investors, and policymakers in the field of therapeutic mAbs

As the most potent antigen-presenting cells, dendritic cells (DCs) are pivotal players in regulating immune responses. DC-based technologies have generated a series of typical and promising therapeutic options, especially after the first DC-based cancer vaccine was approved by US. Food and Drug Administration (US. FDA). In this context, this paper employs patents and citation networks to conduct a fundamental analysis in order to show overall landscape of DC-based technologies. The results in this research can be used as references for decision-making in developing efficacious DC therapeutic products.

Introduction: The fungal disease phaeohyphomycosis tends to occur in immunosuppressed individuals and has rarely been reported to be caused by Phialophora verrucosa. Case presentation: Here, we report a primary subcutaneous phaeohyphomycosis case caused by P. verrucosa in an immunocompromised Chinese female with a CARD9 mutation that was cured with local resection and further treated with itraconazole. The current case is placed in perspective with a review of the relevant literature. The patient presented with painless dark erythema and a plaque on the right part of her face that had been present for the past 20 years. Histological examinations revealed multiple brown hyphae, bead‐like pseudohyphae and yeast‐like cells either within the giant cell or distributed in the dermis and subcutaneous tissues. The fungal cultures were morphologically identified as P. verrucosa and were confirmed by internal transcribed spacer region nucleotide sequencing. A partial surgical focal excision was performed, and the patient was treated with oral itraconazole 200 mg daily for 1 year as maintenance therapy, resulting in complete resolution of the lesions. Conclusion: This case is notable due to the prolonged course before a definitive diagnosis was made, the rarity of P. verrucosa as the cause of subcutaneous phaeohyphomycosis and the dramatic improvement after the focal lesion was excised and treated with itraconazole.

A comprehensive understanding of the integrative nature of the molecular network in thrombosis would be very helpful to develop multicomponent and multitarget antithrombosis drugs for use in traditional Chinese medicine (TCM). This paper attempts to comprehensively map the molecular network in thrombosis by combining platelet signaling, the coagulation cascade, and natural clot dissolution systems and to analyze the topological characteristics of the network, including the centralities of nodes, network modules, and network robustness. The results in this research advance understanding of functions of proteins in the thrombosis network and provide a reference for predicting potential therapeutic antithrombotic targets and evaluating their influence on the network.

Alzheimer's disease (AD) is a serious illness with dramatically increasing incidence. Tremendous worldwide efforts have been exerted to find better ways to treat the disease, delay its onset and prevent it from progressing. In order to discover future anti-AD medicines more rationally, it is crucial to understand the evolving process of existing related technologies from the perspective of technology flow.Patent citation has been used broadly as a powerful tool to capture technology flows. This study collects patent data from IMS Health databases on anti-AD drugs, both marketed and in the research and development (RD) pipeline. In all, 329 US patents from 1978 through 2013 and citations between them are analyzed, in addition to patents related to marketed drugs.To discover effective agents for AD treatment, one promising strategy is to integrate various technology clusters related to anti-AD drugs in terms of the extremely dispersed patent citation network in this area. In this context, governments should pay more attention to encourage basic research, especially to focus on cross-mechanism anti-AD agents. New theories and targets for AD, such as the tau protein hypothesis, are worthy of researcher note. Drugs targeting β-amyloid peptide theory show promise for investors.

By using 2-N,6-O-sulfated chitosan (26SCS) immobilized poly(lactide-co-glycolide) (PLGA) scaffolds, our system achieved controlled release and improved bioactivity of recombinant human bone morphology protein-2 (rhBMP-2). Initially aminolyzed by ethylenediamine, PLGA scaffolds surface was immobilized with 26SCS via electrostatic assembly. Upon the presence of 26SCS, the system displayed improved rhBMP-2 adsorption and prolonged release process in vitro due to the high affinity of rhBMP-2 with 26SCS. On the other hand, because of incorporation of 26SCS, the system appeared to be more hydrophilic and provided a better environment for cells attachment. Moreover, 26SCS enhanced the binding efficiency between rhBMP-2 and its receptors as well as alkaline phosphatase activity. Our study highlights 26SCS immobilized PLGA scaffolds may be excellent candidates for use in bone tissue engineering.

Chimeric genes resulting from the rearrangement of a mitochondrial genome were generally thought to be a causal factor in the occurrence of cytoplasmic male sterility (CMS). In the study, earlier we reported that identifying a 47 bp deletion at 3'- flanking of atp9 that was linked to male sterile cytoplasm in kenaf. The truncated fragment was fused with atp9, a mitochondrial transit signal (MTS) and/or GFP, comprised two chimeric genes MTS-HM184-GFP and MTS-HM184. The plant expression vector pBI121 containing chimeric genes were then introduced to tobacco plants by Agrobacterium-mediated T-DNA transformation. The result showed that certain transgenic plants were male sterility or semi-sterility, while some were not. The expression analysis further demonstrated that higher level of expression were showed in the sterility plants, while no expression or less expression in fertility plants, the levels of expression of semi-sterility were in between. And the sterile plant (containing MTS-HM184-GFP) had abnormal anther produced malformed/shriveled pollen grains stained negative that failed to germinate (0%), the corresponding fruits was shrunken, the semi-sterile plants having normal anther shape produced about 10-50% normal pollen grains, the corresponding fruits were not full, and the germination rate was 58%. Meanwhile these transgenic plants which altered on fertility were further analyzed in phenotype. As a result, the metamorphosis leaves were observed in the seedling stage, the plant height of transgenic plants was shorter than wild type. The growth duration of transgenic tobacco was delayed 30-45 days compared to the wild type. The copy numbers of target genes of transgenic tobacco were analyzed using the real-time quantitative method. The results showed that these transgenic plants targeting-expression in mitochondrial containing MTS-HM184-GFP had 1 copy and 2 copies, the other two plants containing MTS-HM184 both had 3 copies, but 0 copy in wild type. In summary, the two manual chimeric genes might be related to male sterility in kenaf.

Traditional Chinese medicine (TCM) is a distinct medical system that deals with the life–health–disease–environment relationship using holistic, dynamic, and dialectical thinking. However, reductionism has often restricted the conventional studies on TCM, and these studies did not investigate the central concepts of TCM theory about the multiple relationships among life, health, disease, and environment. Complex network analysis describes a wide variety of complex systems in the real world, and it has the potential to bridge the gap between TCM and modern science owing to the holism of TCM theory. This article summarizes the current research involving TCM network analysis and highlights the computational tools and analysis methods involved in this research. Finally, to inspire a new approach, the article discussed the potential problems underlying the application of TCM network analysis.

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression.

Metastasis is the primary mediator of prostate cancer (PCA) lethality and poses a significant clinical obstacle. The identification of factors involved in the metastasis of PCA is imperative. We demonstrate herein that trefoil factor 1 (TFF1) promotes PCA cell migration and invasion in vitro and metastasis in vivo. The capacity of TFF1 to enhance cell migration/invasion is mediated by transcriptional repression of E-CADHERIN. Consideration of targeted inhibition of TFF1 to prevent metastasis of prostate carcinoma is warranted.

Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.

We herein demonstrate an oncogenic role for signal transducer and activator of transcription (STAT)-3alpha (the full length STAT3 isoform), which also mediates autocrine human GH (hGH)-stimulated oncogenicity, in human endometrial carcinoma (EC) cells. Autocrine hGH stimulated Y705 phosphorylation of STAT3 and STAT3-mediated transcriptional activity in a SRC and Janus-2 Kinase dependent manner in human EC cell lines. Forced expression of a constitutively active variant of STAT3alpha increased proliferation, anchorage-independent, three-dimensional (3D) Matrigel, and xenograft growth and promoted epithelial-mesenchymal transition, migration, and invasion of EC cells. Conversely, the oncogenic capacity of EC cells was significantly impaired by treatment with JSI-124, an inhibitor of STAT3 phosphorylation and activity, small interfering RNA-mediated depletion of STAT3alpha, or a dominant-negative variant of STAT3alpha. Furthermore, the enhanced EC cell oncogenicity stimulated by autocrine hGH, was also abrogated by functional inhibition or small interfering RNA-mediated depletion of STAT3alpha. STAT3alpha may therefore be a common mediator of oncogenic signaling pathways stimulating progression of EC.

We herein show that Artemin (ARTN), one of the glial cell line–derived neurotrophic factor family of ligands, promotes progression of human non–small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplastic compared with normal lung tissues; increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were highly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA–mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC. Mol Cancer Ther; 9(6); 1697–708. ©2010 AACR.

Increased activation of signal transducer and activator of transcription (STAT)-5 has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cell lines MCF-7 and T47D. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of human mammary carcinoma cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.

The B-factors of crystal structures reflect the atomic fluctuations about their average positions and provide important information about molecular dynamics. Although numerous works have been addressed on theoretical and computational studies of B-factor profile of protein atoms, the methods used for predicting B-factor values of water molecules in protein crystals still remain unexploited. In this article, we describe a new approach that we named local hydrophobic descriptors (LHDs) to characterize the hydrophobic landscapes of protein hydration sites. Using this approach coupled with partial least squares (PLS) regression and least-squares squares support vector machine (LSSVM), we perform a systematic investigation on the linear and nonlinear relationships between the LHDs and water B-factors. Based upon an elaborately selected, large-scale dataset of crystal water molecules, our method predicts B-factor profile with coefficient of determination rpred of 0.554. We demonstrate that (i) the dynamics of water molecules is primarily governed by the local features of hydrophobic potential landscapes, and (ii) the accuracy of predicted B-factor values depends on water packing density.

Aiming at the problems that a role-mapping process isn't related to role-spliting and evaluation methods, a theoretical support of role-spliting is put forward. Role-spliting is evaluated on three aspects based on ontology: excess rate of permission, split rate of role, destructive degree of role hierarchies. An entire algorithm of role-spliting is given. The feasibility of role-spliting is illustrated by an example. It is shows quantitatively that role-spliting is effective on role mapping of inter-domain and role hierarchy, and will be effective on modification of permission assignment, dipartition of lower-roles and adjustment of the whole role hierarchy.