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With the development of society and the Internet and the advent of the cloud era, people began to pay attention to big data. The background of big data brings opportunities and challenges to the research of urban intelligent transportation networks. Urban transportation system is one of the important foundations for maintaining urban operation. The rapid development of the city has brought tremendous pressure on the traffic, and the congestion of urban traffic has restricted the healthy development of the city. Therefore, how to improve the urban transportation network model and improve transportation and transportation has become an urgent problem to be solved in urban development. Specific patterns hidden in large-scale crowd movements can be studied through transportation networks such as subway networks to explore urban subway transportation modes to support corresponding decisions in urban planning, transportation planning, public health, social networks, and so on. Research on urban subway traffic patterns is crucial. At the same time, a correct understanding of the behavior patterns and laws of residents' travel is a key factor in solving urban traffic problems. Therefore, this paper takes the metro operation big data as the background, takes the passenger travel behavior in the urban subway transportation system as the research object, uses the behavior entropy to measure the human behavior, and actively explores the urban subway traffic mode based on the metro passenger behavior entropy in the context of big data. At the same time, the congestion degree of the subway station is analyzed, and the redundancy time optimization model of the subway train stop is established to improve the efficiency of the subway operation, so as to provide important and objective data and theoretical support for the traveler, planner and decision maker. Compared to the operation graph without redundant time, the total travel time optimization effect of passengers is 7.74%, and the waiting time optimization effect of passengers is 6.583%. [ABSTRACT FROM AUTHOR]

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N -acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies. [ABSTRACT FROM AUTHOR]

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N -acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies. [ABSTRACT FROM AUTHOR]

The Taiwanese government has been facing severe challenges pressed by population ageing. The government started taking the issue of long-term care seriously since the first rotation of the political parties in 2000. However, early plans for long-term care were limited in terms of coverage. The Long-Term Care 2.0 Plan"a tax-funded, universal plan"was implemented in 2016. Soon after its implementation, the number of service organizations and the coverage of service increased sharply. This paper takes Taiwan as an example to discuss the designs of long-term care, and strategies to expand services. With many countries currently under pressure in long term care needs, Taiwan's experience could serve as a good example on how to achieve such policy goal within a short period of time. In addition, policy challenges for expanding long-term care are discussed. [ABSTRACT FROM AUTHOR]

We identified 78 imported chikungunya cases in Taiwan during 2006-2014. Sixty-six (84.6%) cases were initially suspected to be dengue, which indicates the necessity for laboratory diagnostics in differentiation between dengue and chikungunya. Results also emphasize the need for active surveillance of febrile illness at points of entry. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicle (UAV) can be utilized as a relay to connect nodes with long distance, which can achieve significant throughput gain owing to its mobility and line-of-sight (LoS) channel with ground nodes. However, such LoS channels make UAV transmission easy to eavesdrop. In this paper, we propose a novel scheme to guarantee the security of UAV-relayed wireless networks with caching via jointly optimizing the UAV trajectory and time scheduling. For every two users that have cached the required file for the other, the UAV broadcasts the files together to these two users, and the eavesdropping can be disrupted. For the users without caching, we maximize their minimum average secrecy rate by jointly optimizing the trajectory and scheduling, with the secrecy rate of the caching users satisfied. The corresponding optimization problem is difficult to solve due to its non-convexity, and we propose an iterative algorithm via successive convex optimization to solve it approximately. Furthermore, we also consider a benchmark scheme in which we maximize the minimum average secrecy rate among all users by jointly optimizing the UAV trajectory and time scheduling when no user has the caching ability. Simulation results are provided to show the effectiveness and efficiency of our proposed scheme. [ABSTRACT FROM AUTHOR]

A total of 1,596 laboratory-confirmed imported dengue cases were identified in Taiwan during 2011–2016. Most of the imported cases arrived from Southeast Asia as well as the Indian subcontinent, the Pacific region, Latin America, Australia and Africa. Phylogenetic analyses of the complete envelope protein gene sequences from 784 imported dengue virus (DENV) isolates were conducted, and the results suggest that the DENV-1 genotype I and DENV-2 Cosmopolitan genotype comprise the predominant serotype/genotype of DENV strains circulating in Southeast Asia. The DENV-1 genotype III, DENV-3 genotype III and DENV-4 genotype I and II strains were found to be newly emerging in several Southeast Asian countries. Our results also showed that geographical restrictions of DENV-1 genotype I, DENV-1 genotype III and DENV-2 Cosmopolitan genotype are becoming blurred, indicating the extensive introductions and continuous expansions of DENV strains between nations in Southeast Asia. In this study, we present the geographic distribution and dynamic transmission of DENV strains circulating in Southeast Asian countries. In addition, we demonstrated local dengue epidemics caused by several imported DENV strains in Taiwan during 2011–2016. [ABSTRACT FROM AUTHOR]

In future mobile networks, it is difficult for static base stations (BSs) to support the rapidly increasing data services, especially for cell-edge users. Unmanned aerial vehicle (UAV) is a promising method that can assist BSs to offload the data traffic, due to its high mobility and flexibility. In this correspondence, we focus on the UAV trajectory at the edges of three adjacent cells to offload traffic for BSs. In the proposed scheme, the sum rate of UAV-served edge users is maximized subject to the rate requirements for all the users, by optimizing the UAV trajectory in each flying cycle. The optimization is a mixed-integer nonconvex problem, which is difficult to solve. Thus, it is transformed into two convex problems, and an iterative algorithm is proposed to solve it by optimizing the UAV trajectory and edge user scheduling alternately. Simulation results are presented to show the effectiveness of the proposed scheme. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicles (UAVs) can help small-cell base stations (SBSs) offload traffic via wireless backhaul to improve coverage and increase rate. However, the capacity of backhaul is limited. In this paper, UAV assisted secure transmission for scalable videos in hyper-dense networks via caching is studied. In the proposed scheme, UAVs can act as SBSs to provide videos to mobile users in some small cells. To reduce the pressure of wireless backhaul, UAVs and SBSs are both equipped with caches to store videos at off-peak time. To facilitate UAVs, a single antenna is equipped at each UAV and thus, only the precoding matrices of SBSs should be cooperatively designed to manage interference by exploiting the principle of interference alignment. On the other hand, the SBSs replaced by UAVs will be idle. Thus, in order to guarantee secure transmission, the idle SBSs can be further exploited to generate jamming signal to disrupt eavesdropping. The jamming signal is zero-forced at the legitimate users through the precoding of the idle SBSs, without affecting the legitimate transmission. The feasibility conditions of the proposed scheme are derived, and the secrecy performance is analyzed. Finally, simulation results are presented to verify the effectiveness of the proposed scheme. [ABSTRACT FROM PUBLISHER]

Patients with prostate cancer and systemic lupus erythematosus exhibit reduced DNase I activity, and patients with myocardial infarction exhibit increased DNase I activity. So the assay of DNase I is of high importance. A colorimetric assay is described here for the determination of the activity of DNase. It is based on strand scission of dsDNA as catalyzed by DNase I. The products of digestion (nucleoside monophosphates) can better stabilize citrate capped AuNPs than dsDNA. In the absence of DNase I, the AuNPs aggregate in presence of NaCl and then display a blue color. In the presence of the analyte (DNase I), AuNPs do not aggregate but rather remain dispersed and display a red color. These findings were exploited to design a DNase I activity assay that is based on the measurement of ratio of absorbances at 520 nm (red) to 650 nm (blue). The detection limit for DNase I activity is found to be 7.1 U⋅L. In our perception, this assay has a large potential with respect to diagnoses of DNase I activity-related diseases and in drug screening. [ABSTRACT FROM AUTHOR]

Soya hull, an underutilised coproduct of soya processing, was investigated as a source of disulphide-rich bioactive proteins. A Viscozyme L-assisted extraction method was developed to improve the yield of extracted proteins. The extracted proteins were identified by MALDI TOF- TOF MS, and the most abundant disulphide-rich protein among identified proteins was purified and the enzymatic properties were evaluated. The results indicated that the Viscozyme L-assisted extraction method extracted significantly ( P < 0.05) more proteins (39.01%) than did the aqueous method (4.52%). The yield of the purified aspartic proteinase nepenthesin-1-like [ Glycine max] (Gm APN1K) (the most abundant disulphide-rich protein) is 570 mg Kg−1. The specific activity of Gm APN1K was 62.1 U mg−1 at pH 3.0 and 37 °C. The enzyme was optimally active at pH 3.0 and 55 °C. It was stable within pH range 3.0-10.0 and up to 55 °C, respectively, and was specifically inhibited by pepstatin A. [ABSTRACT FROM AUTHOR]

Surface-active pectin was efficiently extracted from soya hull using phosphate-assisted subcritical water combined with ultrasonic treatment (PASW-UT). The physicochemical and functional properties of soya hull pectin (PSHP) were evaluated. Compared to pectin prepared by traditional acid extraction (ASHP), the yield and purity of PSHP were significantly increased, as well as PSHP also contained more protein moiety and displayed better emulsifying and foaming properties. However, the emulsifying and foaming properties of protein-depleted soya bean hull pectin (PDSHP) were markedly decreased as compared to PSHP, which was supported by data of dynamic interfacial tension of pectins, suggesting that the emulsifying and foaming capacity of PSHP should be mainly ascribed to the existence of more extensin, as evidenced by the results of hydroxyproline content. In further comparison with commercial sugar beet pectin (SBP), the PSHP exhibited similar emulsifying properties with SBP over the pH range of 2-6. Moreover, the foam ability and stability were even higher than those of SBP, especially at pH 4.0. These findings suggest that PASW-UT could be used as an effective strategy to prepare novel surface-active pectin from soya hull. [ABSTRACT FROM AUTHOR]

With both in vivo and in vitro experiments, the present study was conducted to investigate the effect of regulatory T cell (Treg) on promoting T-lymphocyte apoptosis and its regulatory mechanism through transforming growth factor-beta (TGF-β1) signaling in mice. A murine model of polymicrobial sepsis was reproduced by cecal ligation and puncture (CLP); PC61 and anti-TGF-β antibodies were used to decrease counts of CD4+CD25+ Tregs and inhibit TGF-β activity, respectively. Splenic CD4+CD25+ Tregs and CD4+CD25− T cells were isolated. Phenotypes, including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), forkhead/winged helix transcription factor p3 (Foxp3), and TGFβ1m+, as well as the apoptotic rate of CD4+CD25− T cell, were analyzed by flow cytometry. Real-time reverse transcription-polymerase chain reaction was performed to determine mRNA expression of TGF-β1, and the expressions of Smad2/Smad3, Bcl-2 superfamily members of Bcl-2/Bim, cytochrome C, the mitochondrial membrane potential, and caspases in CD4+CD25− T cells were simultaneously determined. After treatment with PC61 or anti-TGF-β antibody, CTLA-4, Foxp3, and TGFβ1m+ expressions of CD4+CD25+ Tregs were markedly decreased in comparison to that of the CLP group and the apoptosis rate of CD4+CD25− T cells was significantly positively correlated with the expression of TGF-β1. Meanwhile, levels of P-Smad2/P-Smad3, proapoptotic protein Bim, cytochrome C, and activity of caspase-3, -8, -9 were downregulated, whereas the mitochondrial membrane potential and antiapoptotic protein Bcl-2 expression were restored. Taken together, our data indicated that the TGF-β1 signal could be partly involved in the apoptosis of CD4+CD25− T cells promoted by CD4+CD25+ Tregs, therefore inhibition of TGF-β1 expression may provide a novel strategy for the improvement of host immunosuppression following sepsis. [ABSTRACT FROM AUTHOR]

A novel strategy for the fabrication of a colorimetric aptasensor using label free gold nanoparticles (AuNPs) is proposed in this work, and the strategy has been employed for the assay of adenosine deaminase (ADA) activity. The aptasensor consists of adenosine (AD) aptamer, AD and AuNPs. The design of the biosensor takes advantage of the special optical properties of AuNPs and the interaction between AuNPs and single-strand DNA. In the absence of ADA, the AuNPs are aggregated and are blue in color under appropriate salt concentration because of the grid structure of an AD aptamer when binding to AD, while in the presence of the analyte, AuNPs remain dispersed with red color under the same concentration of salt owing to ADA converting AD into inosine which has no affinity with the AD aptamer, thus allowing quantitative investigation of ADA activity. The present strategy is simple, cost-effective, selective and sensitive for ADA with a detection limit of 1.526 U L−1, which is about one order of magnitude lower than that previously reported. In addition, a very low concentration of the inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) could generate a distinguishable response. Therefore, the AuNP-based colorimetric biosensor has great potential in the diagnosis of ADA-relevant diseases and drug screening. [ABSTRACT FROM AUTHOR]

Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. Author Summary: Japanese encephalitis (JE) is a vector-borne zoonotic disease transmitted by the bite of a Japanese encephalitis virus (JEV) infected mosquito. Japanese encephalitis is an endemic disease in Taiwan. Before 2008, all known JEV isolates collected in Taiwan belonged to Genotype III of JEV. Genotype I JEV strains were first found in northern Taiwan in 2008. In this study, we conducted a survey of JEV in mosquitoes during 2005–2012. A total of 102,633 mosquitoes were collected from pig farms and wetlands. Among the 26 mosquito species collected, 11 tested JEV positive by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus and An. sinensis. Cx. tritaeniorhynchus was the predominant vector species for transmission of JEV in Taiwan. The JEV infection rate of the mosquitoes captured on the pig farms was significantly higher than the rate of those captured in the wetlands, indicating that pigs played an important role in amplifying JEV. A phylogenetic analysis of the envelope gene sequences of JEV isolated from the mosquitoes demonstrated that the predominant JEV genotype shifted from genotype III to genotype I (GI), providing evidence for multiple introductions and transmission cycle maintenance of GI strains in Taiwan during 2008–2012. [ABSTRACT FROM AUTHOR]

Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. [ABSTRACT FROM AUTHOR]

SCUBE3 (signal peptide CUB-EGF-like domain-containing protein 3) belongs to a newly identified secreted and cell membrane- associated SCUBE family, which is evolutionarily conserved in vertebrates. Scube3 is predominantly expressed in a variety of developing tissues in mice such as somites, neural tubes, and limb buds. However, its function during development remains unclear. In this study, we first showed that knockdown of SCUBE3 in C2C12 myoblasts inhibited FGF receptor 4 expression and FGF signaling, thus resulting in reduced myogenic differentiation. Furthermore, knockdown of zebrafish scube3 by antisense morpholino oligonucleotides specifically suppressed the expression of the myogenic marker myod1 within the lateral fast muscle precursors, whereas its expression in the adaxial slow muscle precursors was largely unaffected. Consistent with these findings, immunofluorescent staining of fast but not slow muscle myosin was markedly decreased in scube3 morphants. Further genetic studies identified fgf8 as a key regulator in scube3-mediated fast muscle differentiation in zebrafish. Biochemical and molecular analysis showed that SCUBE3 acts as a FGF co-receptor to augment FGF8 signaling. Scube3 may be a critical upstream regulator of fast fiber myogenesis by modulating fgf8 signaling during zebrafish embryogenesis. [ABSTRACT FROM AUTHOR]

scube1 (signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF domain-containing protein 1), the founding member of a novel secreted and cell surface SCUBE protein family, is expressed predominantly in various developing tissues in mice. However, its function in primitive hematopoiesis remains unknown. In this study, we identified and characterized zebrafish scube1 and analyzed its function by injecting antisense morpholino-oligonucleotide into embryos. Whole-mount in situ hybridization revealed that zebrafish scube1 mRNA is maternally expressed and widely distributed during early embryonic development. Knockdown of scube1 by morpholinooligonucleotide down-regulated the expression of marker genes associated with early primitive hematopoietic precursors (scl) and erythroid (gata1 and hbbe1), as well as early (pu.1) and late (mpo and l-plastin) myelomonocytic lineages. However, the expression of an early endothelial marker fli1a and vascular morphogenesis appeared normal in scube1 morphants. Overexpression of bone morphogenetic protein (bmp) rescued the expression of scl in the posterior lateral mesoderm during early primitive hematopoiesis in scube1 morphants. Biochemical and molecular analysis revealed that Scube1 could be a BMP co-receptor to augment BMP signaling. Our results suggest that scube1 is critical for and functions at the top of the regulatory hierarchy of primitive hematopoiesis by modulating BMP activity during zebrafish embryogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Surveillance for infectious agents carried by mosquitoes is important for predicting the risk of vector-borne infectious diseases. In this study, a method was established to mass-screen mosquitoes for viral infections. The assay detected the viral load of 4 dengue virus (DENV) serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), the Japanese encephalitis virus (JEV), the Sindbis virus and the Chikungunya virus at 1PFU/mL (determined by real-time RT-PCR) in 36.64–43.45 cycles. This method was applied to 75,364 field-captured mosquitoes that were grouped into 10,343 pools. Japanese encephalitis viruses were detected in 25 pools of 906 Culex tritaeniorhynchus females and a single pool of 44 Cx. fuscocephala females. These viruses were isolated from half of the positive pools. Dengue viruses were detected in 2 pools of 43 Aedes aegypti females. Additionally, mosquitoes that were infected orally with dengue viruses in the laboratory were also used to verify the test. The best detection times for individual mosquitoes after being fed virally-contaminated blood were at day 0 and day 10. The number of mosquitoes detected per pool was up to one infected mosquito plus 59 non-infected mosquitoes; the appropriate storage substances for holding samples within 24h included ice cubes and dry ice. This method, combined with a robust and automated RNA-extraction method and a 96 well real-time RT-PCR machine, allows the processing of a large number of samples at once, making it a powerful tool for monitoring simultaneously local and emerging vector-borne infectious diseases of Flaviviruses and Alphaviruses. This study is the first to quantify the viral load in individual mosquitoes over the course of a 16-day extrinsic incubation period. [Copyright &y& Elsevier]

SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) is a novel, secreted, cell surface glycoprotein expressed during early embryogenesis and found in platelet and endothelial cells. This protein is composed of an N-terminal signal pep- tide sequence followed by nine tandemly arranged epidermal growth factor (EGF)-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C terminus. However, little is known about its domain and biological function. Here, we generated a comprehensive panel of domain deletion constructs and a new genetic mouse model with targeted disruption of Scube1 (Scube1Δcub/Δcub) to investigate the domain function and biological significance. A number of cell- based assays were utilized to define the critical role of the spacer region for membrane association and establish that the EGF- like repeats 7-9 are sufficient for the formation of SCUBE1-mediated homophilic adhesions in a calcium-dependent fashion. Biochemical and molecular analyses showed that the C-terminal cysteine-rich motifs and CUB domain could directly bind and antagonize the bone morphogenetic protein activity. Furthermore, genetic ablation of this C-terminal region resulted in brain malformation in the Scube1Δcub/Δcub embryos. Together, our results support the dual roles of SCUBE1 on brain morphogenesis and cell-cell adhesions through its distinct domain function. [ABSTRACT FROM AUTHOR]

Geldanamycin (GA), a heat-shock protein (HSP) 90 inhibitor, induces degradation of HSP90 client proteins, which may promote the presentation of degradation peptides with major histocompatibility complex class I on cancer cells. We hypothesized that GA may enhance the efficacy of DNA vaccination, and investigated the therapeutic effect of the combination of GA and a DNA vaccine against HSP90 clients p185neu and Met. The efficacy of various doses of GA combined with an N-terminal neu (N′-neu) DNA vaccine was investigated in a transplanted tumor constitutively overexpressing endogenous p185neu. Low-dose (2.5 μg) but not high-dose (10 μg) GA enhanced the effect of N′-neu DNA vaccination on the inhibition of murine bladder tumor-2 tumors in syngeneic C3H mice. Anti-p185neu antibody titers were similar among all treated groups. Significantly increased infiltrations of CD8+ T cells and NK cells were observed at tumor sites. GA sensitized tumor cells to the cytotoxic effects of lymphocytes. Depletion of CD8+ T cells eliminated most of the therapeutic efficacy; in contrast, depletion of CD4+ T cells enhanced the therapeutic efficacy. A similar enhancing effect was observed for the combination of GA and a DNA vaccine targeting the Met oncogene. Our results support the use of combination of GA and DNA vaccination against GA-targeted proteins.Molecular Therapy (2007) 15, 404–410. doi:10.1038/sj.mt.6300014 [ABSTRACT FROM AUTHOR]

Abstract: We examined the therapeutic efficacy of xenogenic human N′-terminal neu DNA vaccine and autologous mouse N′-terminal neu DNA vaccine on MBT-2 tumor cells in C3H mice. Intramuscular injection of xenogenic and autologous neu DNA vaccines produced comparable therapeutic efficacies. Mouse and human N′-neu DNA vaccine induced tumor infiltration of CD8+ T cells, while the human vaccine was less effective at stimulating natural killer cells. Depletion of CD8+ T cells abolished the therapeutic efficacy of both types of DNA vaccines. On the other hand, xenogenic neu DNA vaccine showed significantly better therapeutic efficacy than autologous DNA vaccine with gene gun immunization. Increased infiltration of CD8+ T cells was correlated with enhanced therapeutic efficacy in the human N′-neu group of mice. Therefore, intramuscular injection can enhance the therapeutic efficacy of autologous neu DNA vaccine. [Copyright &y& Elsevier]

Abstract: The first attempt to systematically investigate the atmospheric mercury over the territory of Taiwan has been undertaken. Four sampling sites were selected in localities qualified as urban, suburban, industrial-rural and rural ones, within the northern part of Taiwan. The sites were monitored for atmospheric gaseous mercury alternately from September to December 2003 and from April to June 2004, by using a portable automated mercury analyzer Model Gardis-3. The results have shown rather high atmospheric gaseous mercury levels (up to 30 ng/m3 at the urban site, up to 22 ng/m3 at the rural site, up to 24 ng/m3 at the industrial-rural site, and up to 90 ng/m3 at the suburban site) which may indicate the presence of considerably strong point and area mercury sources whose origin still has to be detected more precisely. [Copyright &y& Elsevier]

Abstract: Objective: The aim of the study was to investigate the protein expression and function of a novel secreted protein in the vascular system, named SCUBE1 for signal peptide, CUB (Complement proteins C1r/C1s, Uegf, and Bmp1) and epidermal growth factor-like (EGF)-like domain containing protein 1. Methods and results: Immunohistochemical analysis demonstrated that the SCUBE1 staining is mainly confined to the intravascular platelet-rich thrombus in vascular tissue samples. While quantitative real-time RT-PCR verified that the SCUBE1 mRNA is expressed in human platelets, numerous immunolocalization techniques revealed that the preformed SCUBE1 protein is stored in the α-granules and translocated to the surface upon platelet stimulation. A smaller SCUBE1 fragment, possibly formed by limited proteolysis after being released from the storage granules, was detected in thrombus lysate by Western blot analysis. Interestingly, deposition of SCUBE1 into the subendothelial matrix of the atherosclerotic plaques was evidenced by immunohistochemistry. In addition, studies of platelet adhesion and ristocetin-induced platelet agglutination showed that fragments containing the amino-terminal EGF-like repeats were able to support platelet adhesion and enhance the ristocetin-induced platelet agglutination, respectively. Conclusion: These data suggest that platelet-derived SCUBE1 could function as a novel adhesive molecule and its matrix-bound and soluble fragments may play critical (patho)physiological roles in cardiovascular biology. [Copyright &y& Elsevier]

A letter to the editor about the imported cases of chikungunya disease in Taiwan from 2006 to 2009 is presented.

A letter to the editor is presented in response to an article about two imported chikungunya cases in Taiwan.

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei , concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg−1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-h challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg−1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg−1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei , and an protect shrimp from damage caused by oxidative stress. • Phlorotannins improved the growth, immunity, and antioxidant capacity of L. vannamei. • Phlorotannins improved the intestinal barrier function through shaping the intestinal microbiota of L. vannamei. • Phlorotannins within the range of 2.0 g kg-1 did not cause metabolic or pathological damage to L. vannamei. • The optimal addition amount of phlorotannins is recommended to be 2.0 g kg−1. [ABSTRACT FROM AUTHOR]

Background: Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan.Methods: Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors.Results: A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections.Conclusions: Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures. [ABSTRACT FROM AUTHOR]

Scrub typhus is the most common endemic vector-borne disease in Taiwan. We identified a total of 4,857 laboratory-confirmed cases during 2006–2016 with hyperendemic foci on offshore islands, including Penghu (778 cases, 16.0%) and Kinmen (716 cases, 14.7%), and eastern Taiwan, including Taitung (628 cases, 12.9%) and Hualien (508 cases, 10.5%). Scrub typhus cases occur year-round throughout Taiwan, with a summer peak in June and July. A total of 545 O. tsutsugamushi isolates were successfully obtained from patients infected in diverse geographic areas, including Taiwan and three offshore islands, and the complete open reading frame of the 56 kDa type-specific antigen gene (tsa56) sequence of these isolates was examined. High phylogenetic diversity was found in these isolates, which could be grouped into 36 distinct sequence types. Most isolates belonged to the Karp (49.9%; 272/545), followed by the TW-22 (17.8%; 97/454) and Kawasaki (14.7%; 80/545) genotypes. In conclusion, our data indicate the widespread presence of tsa56 genotypes closely related to Thailand and Korean strains and the presence of the unique endemic strains TW-12, TW-22, TW-29, and TW-36 in Taiwan. Author summary: Scrub typhus is a mite-borne disease and the most common rickettsial disease in the regions including Asia-Pacific, Middle East, and South America. Taiwan is located at the center of the endemic area of scrub typhus, and surveillance of scrub typhus and monitoring of genetic sequences of O. tsutsugamushi are important for disease control and prevention. In this study, we present the results of laboratory-based scrub typhus surveillance in Taiwan during 2006–2016. A total of 4,857 laboratory-confirmed scrub typhus cases were identified. Most of the cases occurred on offshore islands and in eastern Taiwan, including Penghu Island (778 cases, 16.0%), Kinmen Island (716 cases, 14.7%), Taitung County (628 cases, 12.9%) and Hualien County (508 cases, 10.5%). Phylogenetic analyses of the 56-kDa type-specific antigen gene sequence of 545 O. tsutsugamushi strains isolated from scrub typhus patients were conducted. Most isolates belonged to the Karp (49.9%; 272/545) genotype, followed by the TW-22 (17.8%; 97/454) sequence type and Kawasaki (14.7%; 80/545) genotype. Most strains were closely related to strains from Southeast and East Asia, whereas unique isolates were also found in Taiwan. [ABSTRACT FROM AUTHOR]

Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%—100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%—100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%—100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity. [ABSTRACT FROM PUBLISHER]

Objectives: This study investigates the potential application of plasma SCUBE1 [signal peptide–CUB (complement C1r/C1s, Uegf, and Bmp1)–EGF (epidermal growth factor)-like domain-containing protein 1] as a biomarker of platelet activation in acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Background: Platelet activation plays a crucial role in ACS and AIS. Platelet stimulation is associated with increased plasma concentration of SCUBE1, a novel platelet-endothelial secreted protein identified in our previous study. Methods: Plasma concentrations of SCUBE1 from 40 ACS and 40 AIS patients were measured by enzyme-linked immunoadsorbent assay and compared with the levels of 40 healthy control subjects and 83 chronic coronary artery disease (CAD) patients. Two-dimensional electrophoresis followed by Western blotting was used to characterize SCUBE1 protein in patients'' plasma. Results: Plasma SCUBE1 concentration was virtually undetectable in healthy control subjects and CAD patients, but was significantly higher in ACS and AIS patients (median = 205 and 95.1 ng/ml, respectively, p < 0.01). The increase in plasma SCUBE1 was detectable in the plasma as early as 6 h after the onset of symptoms and remained detectable up to 84 h. Plasma SCUBE1 concentration is an independent predictor of stroke severity based on National Institutes of Health Stroke Scale (β = 3.18, p < 0.001). Furthermore, smaller SCUBE1 fragments were detected in ACS patients'' plasma, suggesting that plasma SCUBE1 might subject to a proteolytic regulation under pathological conditions. Conclusions: Plasma SCUBE1 concentration is significantly elevated in ACS and AIS but not CAD patients. Plasma SCUBE1 is a potential biomarker of platelet activation in acute thrombotic disease. [Copyright &y& Elsevier]

DNA vaccine represents a novel method to elicit immunity against infectious disease. Lipopolysaccharide (LPS) copurified with plasmid DNA may affect therapeutic efficacy and immunological response. We aimed to study the effect of LPS on the therapeutic efficacy of HER-2/neu DNA vaccine in a mouse tumor animal model. Plasmid DNA purified from commercial EndoFree plasmid purification kits functioned as a better therapeutic DNA vaccine than that purified from Non-EndoFree purification kit, which contains 0.5 g LPS per 100 mg DNA plasmid. To further investigate the effect of LPS on the therapeutic efficacy of DNA vaccine, increasing amount of LPS was added to endotoxin-free plasmid DNA, and inoculated on mice with established tumors. One g of LPS significantly attenuated the therapeutic effect of neu DNA vaccine and increased Th2 immune responses bias with interleukin-4 cytokine production. In contrast, high amount (100 g) of LPS enhanced the therapeutic efficacy of neu DNA vaccine with an increase of cytotoxic T lymphocyte response and Th1 immune response. The effect of LPS on DNA vaccine was diminished when the tumor was grown in toll-like receptor 4 (TLR4)mutant C3H/HeJ mice. Our results indicate that variation in the LPS doses exerts opposing effects on the therapeutic efficacy of DNA vaccine, and the observed effect is TLR4 dependent. [ABSTRACT FROM AUTHOR]

Objective: To estimate the lifetime financial burden on Taiwan's national health insurance (NHI) system, life expectancy and years of life expectancy lost (YLEL) attributable to smoking from major smoking related diseases. Methods: 10 major smoking related diseases (seven cancers, stroke, acute myocardial infarction and chronic obstructive pulmonary disease) were selected for this study. A survival analysis was conducted on linked cohorts from the National Death Registry database and the National Cancer Registry (NCR) and patients at the National Taiwan University Hospital (NTUH). Estimation of the smoking attributable fraction (SAF) for the study diseases was undertaken by combining the relative risks of smokers against non-smokers and the prevalence of smoking in Taiwan. The YLEL attributable to smoking was calculated for the study diseases by combining the survival analysis results, the SAF and the annual incidences of each disease. The lifetime medical expenditure for the study diseases was estimated by integrating the survival curve and the mean annual medical costs calculated from NHI reimbursement records. Results: There were 241 280 incidents of the 10 study diseases in 2001, of which about 53 648 cases (22.2%) were attributable to smoking, with a total YLEL of 191 313 at an average of about 3.6 YLEL per case. For each case, the average survival time was about 10.2 years. Under two different annual discount rates, the total lifetime financial burden on the NHI was estimated at between $291 million (£147 million; €216 million) (3% discount) and $336 million (1% discount) for all diseases attributable to smoking in 2001, accounting for about 24.6% of the total estimated lifetime medical expenditure for all incidents of the 10 study diseases. Conclusions: Smoking places tremendous financial and health burdens upon both society and individuals. A much more stringent tobacco control strategy is needed to curb the damage from smoking. [ABSTRACT FROM AUTHOR]

The structural transition temperature T t increases largely with the introduction of Si in Mn 0.9 Cu 0.1 CoGe 1- x Si x alloys due to the enhancement of degree of hexagonal distortion. Thus, the first-order magnetostructural transformation from ferromagnetic orthorhombic to paramagnetic hexagonal phase can be obtained in the range of 0.15 < x < 0.21. Large magnetocaloric effect (MCE) under low magnetic field change of 2 T is obtained due to the magnetostructural transformation, e.g., the maximum magnetic entropy change (-Δ S M ) value for x = 0.16 is 10.3 J/kg K at 297 K, which is comparable to or even larger than those of some typical room-temperature magnetocaloric materials. The nature of magnetostructural transition has been studied by different methods, and it is found that the Arrott plots fail to determine the order of phase transition. In contrast, the universal curve of Δ S M is proved to be a more effective criterion to distinguish the order of phase transition. Besides, a linear relationship between -Δ S M and Δ μ 0 H is found, and so the -Δ S M values for higher field changes can be estimated by linear fitting. Consequently, large MCE induced by magnetostructural transformation suggests that Mn 0.9 Cu 0.1 CoGe 1- x Si x alloys could be promising candidates for room-temperature magnetocaloric materials. [ABSTRACT FROM AUTHOR]

It should read as follows: This work was supported by grants MOHW105-CDC-C-315-122110(PYS) and MOHW106-CDC-C-315-113112(PYS) from Centers for Disease Control, Ministry of Health and Welfare, Taiwan, Republic of China. Reference 1 Chen H- F, Peng S- H, Tsai K- H, Yang C- F, Chang M- C, Hsueh Y- L, et al. (2022) Molecular epidemiology of scrub typhus in Taiwan during 2006-2016. Correction: Molecular epidemiology of scrub typhus in Taiwan during 2006-2016. [Extracted from the article]

Background: Clinical experience and animal studies have suggested that positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose (18F-FDG) may be promising for imaging of bone infections. In this study, we aimed to establish the accuracy of 18F-FDG PET scanning for monitoring the response to poly(lactide-co-glycolide) (PLGA) vancomycin beads for treatment of bone infection. Methods: PLGA was mixed with vancomycin and hot-compress molded to form antibiotic beads. In vitro, elution assays and bacterial inhibition tests were employed to characterize the released antibiotics. In vivo, cylindrical cavities were made in six adult male New Zealand white rabbits, and Staphylococcus aureus or saline was injected into the cavity to create a bone infection. After 2 weeks, the infection was confirmed by bacterial cultures, and the defect was filled with PLGA vancomycin beads. The treatment response was monitored by 18F-FDG PET. Results: The biodegradable beads released high concentrations of vancomycin (well above the breakpoint sensitivity concentration) for treatment of bone infection. In bacterial inhibition tests, the diameter of the sample inhibition zone ranged from 6.5 to 10 mm, which was equivalent to 12.5-100 % relative activity. 18F-FDG PET results showed that uncomplicated bone healing was associated with a temporary increase in 18F-FDG uptake at 2 weeks, with return to near baseline at 6 weeks. In the infected animals, localized infection resulted in intense continuous uptake of 18F-FDG, which was higher than that in uncomplicated healing bones. Bone infection was confirmed with positive bacterial cultures. In vancomycin-treated animals, data showed rapidly decreasing amounts of 18F-FDG uptake after treatment. Conclusions: In vitro and in vivo analyses showed that the use of biodegradable PLGA vancomycin beads successfully eradicated S. aureus infection in damaged bone. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitor gefitinib is effective against lung cancer cells carrying mutant epidermal growth factor receptor (EGFR); however, it is not effective against lung cancer carrying normal EGFR. The breaking of immune tolerance against self epidermal growth factor receptor with active immunization may be a useful approach for the treatment of EGFR-positive lung tumors. Xenogeneic EGFR gene was demonstrated to induce antigen-specific immune response against EGFR-expressing tumor with intramuscular administration. Methods: In order to enhance the therapeutic effect of xenogeneic EGFR DNA vaccine, the efficacy of altering routes of administration and formulation of plasmid DNA was evaluated on the mouse lung tumor (LL2) naturally overexpressing endogenous EGFR in C57B6 mice. Three different combination forms were studied, including (1) intramuscular administration of noncoating DNA vaccine, (2) gene gun administration of DNA vaccine coated on gold particles, and (3) gene gun administration of non-coating DNA vaccine. LL2-tumor bearing C57B6 mice were immunized four times at weekly intervals with EGFR DNA vaccine. Results: The results indicated that gene gun administration of non-coating xenogenic EGFR DNA vaccine generated the strongest cytotoxicty T lymphocyte activity and best antitumor effects. CD8(+) T cells were essential for anti-tumor immunityas indicated by depletion of lymphocytes in vivo. Conclusion: Thus, our data demonstrate that administration of non-coating xenogenic EGFR DNA vaccine by gene gun may be the preferred method for treating EGFR-positive lung tumor in the future. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to investigate in a transgenic animal model the cardiac expression and function of a novel extracellular protein SCUBE3 [signal peptide-CUB (complement proteins C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein 3]. Methods and results: Real-time quantitative reverse transcriptase (RT)-PCR analysis showed that SCUBE3 is expressed in the ventricular myocardium. Male transgenic (TG) mice overexpressing SCUBE3 appeared normal during development, from birth to adulthood. However, echocardiography and histopathological examination revealed significant cardiac hypertrophy in TG animals as they aged, at 8 months. Interestingly, left-ventricle hypertrophy occurred more rapidly and more severely under pressure overload in TG mice, as compared to age-matched wild-type littermates. Induced SCUBE3 expression, together with elevated transforming growth factor (TGF)-β1 level under pressure overload, may account for the accelerated onset and progression of cardiac hypertrophy in TG mice. Furthermore, biochemical and molecular studies revealed that the carboxyl-terminal portion of SCUBE3 could physically interact with TGF-β1 and promote the TGF-β1-mediated transcriptional activation. Conclusion: This report is the first demonstration that SCUBE3 may play a role in the regulation of cardiac growth and remodeling responses, possibly through the stabilization of the TGF-β1 signaling pathway. [Copyright &y& Elsevier]

The purpose of the Elderly Nutrition and Health Survey in Taiwan (1999-2000) was to assess the diet, nutrition and health of persons aged 65 and above in Taiwan. A multi-staged, stratified, clustered probability sampling scheme was used in the survey. The survey population was stratified into a total of 13 strata. The four strata of "Hakka areas", "Mountain areas", "Eastern areas", and "PengHu islands" were unique in their ethnicity or geographic locations. The remaining areas of Taiwan were stratified into "Northern", "Central", and "Southern" parts. Within these 3 strata, then each was subdivided into a further 3 strata based on population density. The household interview of the survey was arranged such that effect of seasonal variation was taken into account. A total of 1,937 persons completed the interview and 2,432 persons completed the health exam. The following data were collected: (1) Interview data : household information, basic demographics, 24 hour dietary recall, food frequency and habit, knowledge, attitudes and practice medical history, 36-item Short Form for generic health status, and physical activity. (2) Health exam data: blood sample for measurement of nutritional biochemical indicators and complete clinical chemistry profile, urine sample for urinary electrolytes, anthropometric measurements, ECG, blood pressure, body temperature, pulmonary function, and an osteoporosis assessment. Data from the survey were analyzed using SUDAAN to adjust, for the design effect and to obtain unbiased estimates of the mean, standard error and confidence intervals. Survey respondents were slightly younger compared to non-respondents; however, after weighting and adjustment with SUDAAN, the education levels and ethnicity of respondents and non-respondents were similar indicating lack of bias. We anticipate that the results of this survey will be of benefit in understanding the nutritional status of the elderly, the relationship between nutrition and health, and factors influencing elderly persons' nutritional status. Furthermore, this information could be used in the development of public health nutrition policy aimed at improving the nutrition and health of the elderly in Taiwan. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of HER2/c-erbB-2/neu DNA immunization on mouse tumor cells expressing exogenous human or rat p185neu but not on mouse tumor cells naturally expressing mouse p185neu has been demonstrated. We investigated the feasibility of using N-terminal rat neu DNA immunization on mouse tumor overexpressing endogenous p185neu and enhancing the therapeutic efficacy of this vaccine by fusion to various cytokine genes, including interleukin-2 (IL-2), interleukin-4 (IL-4), or granulocyte–macrophage colony-stimulating factor. In a therapeutic model, N′-neu-IL-2 DNA vaccine was significantly better than N′-neu DNA vaccine, and N′-neu DNA vaccine was significantly better than control DNA or N′-neu-IL-4 DNA vaccine. The therapeutic efficacy of DNA vaccines was correlated with tumor infiltration of CD8+ T cells. Depletion of CD8+ T cells completely abolished the therapeutic effects of N′-neu-IL-2 DNA vaccine and N′-neu DNA vaccine. Depletion of CD4+ T cells after tumor implantation had no influence on N′-neu-IL-2 DNA vaccine, but enhanced the therapeutic efficacy of N′-neu DNA vaccine. Our results demonstrate that rat N′-neu DNA vaccine has a therapeutic effect on established tumor through the CD8+ T-cell-dependent pathway. Depletion of CD4+ T cells or fusion to the IL-2 gene can thus further enhance the therapeutic effects of N′-neu DNA immunization on mouse tumor expressing endogenous p185neu. [Copyright &y& Elsevier]

Designed from combining the structural features of Raf inhibitory azastilbene 7 and EGFR/VEGFR inhibitory 4-anilinoquinazolines 1 – 3 , 4-(3-hydroxyanilino)-6-(1 H -1,2,3-triazol-4-yl)quinazoline 9m exhibited potent and selective inhibitory activity toward B-Raf (IC 50 : 57 nM) and B-RafV600E (IC 50 : 51 nM) over C-Raf (IC 50 : 1.0 μM). Compound 9m also actively inhibited EGFR (IC 50 : 73 nM) and VEGFR2 (IC 50 : 7.0 nM) but not EGFRT790M and PDGFR-β (IC 50 > 10 μM). [Display omitted] • 4-Anilinoquinazoline 9m is a selective B-Raf/B-RafV600E kinase inhibitor. • The IC 50 of 9m for B-Raf and B-RafV600E are 57 and 51 nM, respectively. • 9m is less active for C-Raf with IC 50 of 1.0 μM (~20 × selectivity). • 9m potently inhibits EGFR (IC 50 : 73 nM) and VEGFR2 (IC 50 : 7.0 nM). • 9m binds to the inactive conformations of B-Raf kinases. This paper presents the design and synthesis of 4-(3-hydroxyanilino)-6-(1 H -1,2,3-triazol-4-yl)quinazolines of scaffold 9 as selective B-Raf/B-RafV600E and potent EGFR/VEGFR2 kinase inhibitors. Total 14 compounds of scaffold 9 having different side chains at the triazolyl group with/without fluoro substituents at the anilino group were synthesized and investigated. Among them, 9m with a 2-carbamoylethyl side chain and C-4′/C-6′ difluoro substituents was the most potent, which selectively inhibited B-Raf (IC 50 : 57 nM) and B-RafV600E (IC 50 : 51 nM) over C-Raf (IC 50 : 1.0 μM). Compound 9 m also actively inhibited EGFR (IC 50 : 73 nM) and VEGFR2 (IC 50 : 7.0 nM) but not EGFRT790M and PDGFR-β (IC 50 : >10 μM). Despite having good potency for B-Raf and B-RafV600E in the enzymatic assays, 9m was less active to inhibit melanoma A375 cells which proliferate due to constitutively activated B-Raf600E. The inferior activity of 9m for A375 was similar to that of sorafenib (6), suggesting that 9m might bind to the inactive conformations of B-Raf and B-RafV600E. Docking simulations could thus be performed to reveal the binding poses of 9m in B-Raf, B-RafV600E, and VEGFR2 kinases. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the incidence of the Japanese encephalitis virus (JEV) in Taiwan.

The emergence of castration-resistance is one of the major challenges in the management of patients with advanced prostate cancer. Although the spectrum of systemic therapies that are available for use alongside androgen deprivation for treatment of castration-resistant prostate cancer (CRPC) is expanding, none of these regimens are curative. Therefore, it is imperative to apply systems approaches to identify and understand the mechanisms that contribute to the development of CRPC. Using comprehensive proteomic approaches, we show that a glycosylation-related enzyme, alpha (1,6) fucosyltransferase (FUT8), which is upregulated in CRPC, might be responsible for resistance to androgen deprivation. Mechanistically, we demonstrated that overexpression of FUT8 resulted in upregulation of the cell surface epidermal growth factor receptor (EGFR) and corresponding downstream signaling, leading to increased cell survival in androgen-depleted conditions. We studied the coregulatory mechanisms of EGFR and FUT8 expression in CRPC xenograft models and found that castration induced FUT8 overexpression associated with increased expression of EGFR. Taken together, our findings suggest a crucial role played by FUT8 as a mediator in switching prostate cancer cells from nuclear receptor signaling (androgen receptor) to the cell surface receptor (EGFR) mechanisms in escaping castration-induced cell death. These findings have clinical implication in understanding the role of FUT8 as a master regulator of cell surface receptors in cancer-resistant phenotypes. [ABSTRACT FROM AUTHOR]

The synthesis of trisubstituted triazoles involves the conversion of nitriles into imidate intermediates followed by 1,3-dipolar cycloaddition with in situ generated nitrilimines. [ABSTRACT FROM AUTHOR]