Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC₅₀ values of 1.4 μM, 1.2 μM, 0.6 μM, and 2.6 μM, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-activity relationship analysis was discussed based on the experimental data. Full article

China has submitted its nationally determined contribution to peak its energy-related emissions around 2030. To understand how China might develop its economy while controlling CO₂ emissions, this study surveys a number of recent modeling scenarios that project the country’s economic growth, energy mix, and associated emissions until 2050. Our analysis suggests that China’s CO₂ emissions will continue to grow until 2040 or 2050 and will approximately double their 2010 level without additional policy intervention. The alternative scenario, however, suggests that peaking CO₂ emissions around 2030 requires the emission growth rate to be reduced by 2% below the reference level. This step would result in a plateau in China’s emissions from 2020 to 2030. This paper also proposed a deep de-carbonization pathway for China that is consistent with China’s goal of peaking emissions by around 2030, which can best be achieved through a combination of improvements in energy and carbon intensities. Our analysis also indicated that the potential for energy intensity decline will be limited over time. Thus, the peaking will be largely dependent on the share of non-fossil fuel energy in primary energy consumption. Full article

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs) have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA) microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to explore their function. In the current analysis, 89 upregulated and 177 downregulated mRNAs were identified, together with 291 deregulated lncRNAs. Bioinformatic analysis of these RNAs has categorized these RNAs into pathways including arachidonic acid metabolism, circadian rhythm, linoleic acid metabolism, peroxisome proliferator-activated receptor (PPAR) signaling pathway, sphingolipid metabolism, steroid biosynthesis, tryptophan metabolism and tyrosine metabolism were compromised. Quantitative polymerase chain reaction (qPCR) of representative nine mRNAs and eight lncRNAs (named fatty liver-related lncRNA, FLRL) was conducted and this verified previous microarray results. Several lncRNAs, such as FLRL1, FLRL6 and FLRL2 demonstrated to be involved in circadian rhythm targeting period circadian clock 3 (Per3), Per2 and aryl hydrocarbon receptor nuclear translocator-like (Arntl), respectively. While FLRL8, FLRL3 and FLRL7 showed a potential role in PPAR signaling pathway through interaction with fatty acid binding protein 5 (Fabp5), lipoprotein lipase (Lpl) and fatty acid desaturase 2 (Fads2). Functional experiments showed that interfering of lncRNA FLRL2 expression affected the expression of predicted target, circadian rhythm gene Arntl. Moreover, both FLRL2 and Arntl were downregulated in the NAFLD cellular model. The current study identified lncRNA and corresponding mRNA in NAFLD, providing new insight into the pathogenesis of NAFLD. Moreover, we identified a new lncRNA FLRL2, that might participate NAFLD pathogenesis mediated by Arntl. Full article

Background: This study analyzed differences between transparency of information disclosure and related demands from the health service consumer’s perspective. It also compared how health service providers and consumers are associated by different levels of mandatory information disclosure. Methods: We obtained our research data using a questionnaire survey (health services providers, n = 201; health service consumers, n = 384). Results: Health service consumers do not have major concerns regarding mandatory information disclosure. However, they are concerned about complaint channels and settlement results, results of patient satisfaction surveys, and disclosure of hospital financial statements (p < 0.001). We identified significant differences in health service providers’ and consumers’ awareness regarding the transparency of information disclosure (p < 0.001). Conclusions: It may not be possible for outsiders to properly interpret the information provided by hospitals. Thus, when a hospital discloses information, it is necessary for the government to consider the information’s applicability. Toward improving medical expertise and information asymmetry, the government has to reduce the burden among health service consumers in dealing with this information, and it has to use the information effectively. Full article

The concept of greywater recycling and reuse has gradually become one of the most important strategies in water stressed countries. Due to a high population density and uneven rainfall distribution, the annual average rainfall distribution per capita in Taiwan is one fifth of the global average, which makes Taiwan a seriously water-stressed country. This study used the unit of a family of four as the target and reexamined the zoning concepts of water usage areas, followed by integrating pipeline configuration, water storage design and a filtering system to propose an Interior Customized Greywater System (ICGS) which is based on the application for the family unit. This system can be customized and flexibly adjusted according to household space. In order to verify the feasibility and viability of system, this study performed system configuration and design based on real cases and proposed three scenarios to simulate a 20 year life cycle for cost economic analysis. The result reveals that this system has a minimum payback period of 4 years and provides investment incentives. For regions or countries which have higher water cost or are more water stressed, ICGS can significantly improve the processing and utilization of water. Full article

The National Ocean Service (NOS) of National Oceanic and Atmospheric Administration is developing an operational nowcast/forecast system for the Gulf of Maine (GoMOFS). The system aims to produce real-time nowcasts and short-range forecast guidance for water levels, 3-dimensional currents, water temperature, and salinity over the broad GoM region. GoMOFS will be implemented using the Regional Ocean Model System (ROMS). This paper describes the system setup and results from a one-year (2012) hindcast simulation. The hindcast performance was evaluated using the NOS standard skill assessment software. The results indicate favorable agreement between observations and model forecasts. The root-mean-squared errors are about 0.12 m for water level, less than 1.5 °C for temperature, less than 1.5 psu for salinity, and less than 0.2 m/s for currents. It is anticipated to complete the system development and the transition into operations in fiscal year 2017. Full article

This work investigated the spatial profile and source analysis of polycyclic aromatic hydrocarbons (PAHs) in soil that surrounds coal-fired power plants in Xuzhou, China. High-throughput sequencing was employed to investigate the composition and structure of soil bacterial communities. The total concentration of 15 PAHs in the surface soils ranged from 164.87 to 3494.81 μg/kg dry weight. The spatial profile of PAHs was site-specific with a concentration of 1400.09–3494.81 μg/kg in Yaozhuang. Based on the qualitative and principal component analysis results, coal burning and vehicle emission were found to be the main sources of PAHs in the surface soils. The phylogenetic analysis revealed differences in bacterial community compositions among different sampling sites. Proteobacteria was the most abundant phylum, while Acidobacteria was the second most abundant. The orders of Campylobacterales, Desulfobacterales and Hydrogenophilales had the most significant differences in relative abundance among the sampling sites. The redundancy analysis revealed that the differences in bacterial communities could be explained by the organic matter content. They could also be explicated by the acenaphthene concentration with longer arrows. Furthermore, OTUs of Proteobacteria phylum plotted around particular samples were confirmed to have a different composition of Proteobacteria phylum among the sample sites. Evaluating the relationship between soil PAHs concentration and bacterial community composition may provide useful information for the remediation of PAH contaminated sites. Full article

A high beam quality hundred picoseconds single-longitudinal-mode (SLM) laser is demonstrated based on stimulated Brillouin scattering (SBS) pulse compression and aberration compensation. Flash-lamp-pumped Q-switched Nd³⁺:Y₃Al₅O₁₂ (Nd:YAG) SLM laser with Cr⁴⁺:Y₃Al₅O₁₂ (Cr⁴⁺:YAG) as a saturable absorber is used as the seed source. By combining master-oscillator-power-amplifier (MOPA), a compact single-cell with FC-770 as working medium is generated as pulse compressor. The 7.8 ns SLM laser is temporally compressed to about 450 ps, and 200 mJ energy is obtained at 1064 nm without optical damage. The energy stability is better than 3% with beam quality factor M² less than 1.8, which makes this laser system an attractive source for scientific and industrial applications. Full article

There is a growing appreciation within the livestock industry and throughout society that animal stress is an important issue that must be addressed. With implications for animal health, well-being, and productivity, minimizing animal stress through improved animal management procedures and/or selective breeding is becoming a priority. Effective management of stress, however, depends on the ability to identify and quantify the effects of various stressors and determine if individual or combined stressors have distinct biological effects. Furthermore, it is critical to determine the duration of stress-induced biological effects if we are to understand how stress alters animal production and disease susceptibility. Common stress models used to evaluate both psychological and physical stressors in cattle are reviewed. We identify some of the major gaps in our knowledge regarding responses to specific stressors and propose more integrated methodologies and approaches to measuring these responses. These approaches are based on an increased knowledge of both the metabolic and immune effects of stress. Finally, we speculate on how these findings may impact animal agriculture, as well as the potential application of large animal models to understanding human stress. Full article

This study describes HIV disease burden and patterns of drug use before and during incarceration among detainees in Re-education-Through-Labour-Camps (RTLCs) in China. A cross-sectional survey of 576 men and 179 women from three RTLCs was conducted in Guangxi Province, China. Over three-quarters of study participants were detained due to drug-related offences. Over half of the women (n = 313, 54.3%) and two-thirds of men (n = 119, 66.5%) had been previously been incarcerated in a compulsory detoxification treatment centre (CDTC), and around one-third (men n = 159, 27.6%; women n = 50, 27.9%) in a RTLC. Of those surveyed, 49 men (8.5%) and one (0.6%) woman reported ever using drugs while in a CDTC and/or RTLC. Previous incarceration in CDTCs and RTLCs were associated with HIV infection among both male (OR = 2.15 [1.11–4.15]) and female (OR = 3.87 [1.86–9.04]) detainees. Being married/cohabiting with a partner (OR = 0.53, [0.30–0.93]) and being employed (OR = 0.46, [0.22–0.95]) were associated with a reduced odds of HIV infection among male detainees. A significant proportion of RTLC detainees had a history of drug use and a limited number of inmates had used illegal substances whilst in custody. Repeat incarcerations in CDTCs/RTLCs were associated with higher risks of HIV infection. Full article

The growth and development of plants are sensitive to their surroundings. Although numerous studies have analyzed plant transcriptomic variation, few have quantified the effect of combinations of factors or identified factor-specific effects. In this study, we performed RNA sequencing (RNA-seq) analysis on tobacco leaves derived from 10 treatment combinations of three groups of ecological factors, i.e., climate factors (CFs), soil factors (SFs), and tillage factors (TFs). We detected 4980, 2916, and 1605 differentially expressed genes (DEGs) that were affected by CFs, SFs, and TFs, which included 2703, 768, and 507 specific and 703 common DEGs (simultaneously regulated by CFs, SFs, and TFs), respectively. GO and KEGG enrichment analyses showed that genes involved in abiotic stress responses and secondary metabolic pathways were overrepresented in the common and CF-specific DEGs. In addition, we noted enrichment in CF-specific DEGs related to the circadian rhythm, SF-specific DEGs involved in mineral nutrient absorption and transport, and SF- and TF-specific DEGs associated with photosynthesis. Based on these results, we propose a model that explains how plants adapt to various ecological factors at the transcriptomic level. Additionally, the identified DEGs lay the foundation for future investigations of stress resistance, circadian rhythm and photosynthesis in tobacco. Full article

The NOAA National Ocean Service’s (NOS) Northern Gulf of Mexico Operational Forecast System (NGOFS) became operational in March 2012. Implemented with the Finite Volume Coastal Ocean Model (FVCOM) as its core three-dimensional oceanographic circulation model, NGOFS produces a real-time nowcast (−6 h to zero) and six-hourly, two-day forecast guidance for water levels and three-dimensional currents, water temperature and salinity over the northern Gulf of Mexico continental shelf. Designed as a regional scale prediction system, NGOFS lacks sufficient spatial coverage and/or resolution to fully resolve hydrodynamic features in critical seaports and estuaries. To overcome this shortcoming and better support the needs of marine navigation, emergency response, and environmental management, two FVCOM-based, high-resolution, estuary-scale nested forecast modeling systems, namely the Northwest and Northeast Gulf of Mexico Operational Forecast Systems (NWGOFS and NEGOFS), have been developed through one-way nesting in NGOFS. Using the atmospheric forecast guidance from the NOAA (National Oceanic and Atmospheric Administration)/NWS (National Weather Services)’ North American Mesoscale (NAM) Forecast System, US Geological Survey (USGS) river discharge observations, and the NGOFS water level, current, water temperature and salinity as the surface, river, and open ocean boundary forcing, respectively, a six-month model hindcast for the period October 2010–March 2011 has been conducted. Modeled water levels, currents, salinity and water temperature are compared with observations using the NOS standard skill assessment software. Skill assessment scores indicated that NWGOFS and NEGOFS demonstrate improvement over NGOFS. The NWGOFS and NEGOFS are under real-time nowcast/forecast test and evaluation by NOS’s Center for Operational Oceanographic Products and Services (CO-OPS). The forecast systems are scheduled to be implemented operational on NOAA Weather & Climate Operational Supercomputing System (WCOSS) in June 2014. Full article

The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection. Full article

Batteries are one of the most important components in many mechatronics systems, as they supply power to the systems and their failures may lead to reduced performance or even catastrophic results. Therefore, the prediction analysis of remaining useful life (RUL) of batteries is very important. This paper develops a quantitative approach for battery RUL prediction using an adaptive bathtub-shaped function (ABF). ABF has been utilised to model the normalised battery cycle capacity prognostic curves, which attempt to predict the remaining battery capacity with given historical test data. An artificial fish swarm algorithm method with a variable population size (AFSAVP) is employed as the optimiser for the parameter determination of the ABF curves, in which the fitness function is defined in the form of a coefficient of determination (R2). A 4 x 2 cross-validation (CV) has been devised, and the results show that the method can work valuably for battery health management and battery life prediction. Full article

Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC) as well as RTK, the structure-activity relationship (SAR) is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule. Full article

Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD₅₀ values in the range of 45–55 µM for baicalin and 25–40 µM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD₅₀ values of 177 µM for baicalin and 68 µM for baicalein. Baicalin decreased expression of VEGF (20 µM), cMyc (80 µM), and NFkB (20 µM); baicalein decreased expression of VEGF (10 µM), HIF-1α (20 µM), cMyc (20 µM), and NFkB (40 µM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. Full article

4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, they both had inhibition zone sizes of over 25 mm. The results of the absolute concentration susceptibility test suggested that they had inhibitory effects against mycobacteria. Moreover, 4-deoxybostrycin exhibited good inhibition which was even better than that of first line anti-tuberculosis (TB) drugs against some clinical multidrug-resistant (MDR) M. tuberculosis strains. The gene expression profile of M. tuberculosis H37Rv after treatment with 4-deoxybostrycin was compared with untreated bacteria. One hundred and nineteen out of 3,875 genes were significantly different in M. tuberculosis exposed to 4-deoxybostrycin from control. There were 46 functionally known genes which are involved in metabolism, information storage and processing and cellular processes. The differential expressions of six genes were further confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The present study provides a useful experiment basis for exploitation of correlative new drugs against TB and for finding out new targets of anti-mycobacterial therapy. Full article

A spatial approach that incorporates three economic components and one environmental factor has been developed to evaluate the dynamic behaviours of the rural areas at a provincial level. An artificial fish swarm algorithm with variable population size (AFSAVP) is proposed for the spatial problem. A functional region affecting index θ is employed as a fitness function for the AFSAVP driven optimisation, in which a gross domestic product (GDP) based method is utilised to estimate the CO₂ emission of all provinces. A simulation for the administrative provinces of China has been implemented, and the results have shown that the modelling method based on GDP data can assess the spatial dynamic behaviours and can be taken as an operational tool for the policy planners. Full article

N-Acetylhexosamine 1-kinase (NahK) catalyzes the direct addition of a phosphate from adenosine 5'-triphosphate (ATP) to the anomeric position of N-acetylhexosamine and shows similar activity towards N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc). Herein we report the cloning, characterization, and substrate specificity studies of two NahKs from Bifidobacterium infantis ATCC15697 and Bifidobacterium longum ATCC55813, respectively. A new capillary electrophoresis assay method has been developed for enzyme activity assays. Both enzymes have a good expression level in E. coli (180–185 mg/L culture) and can tolerate diverse modifications at C2 of GlcNAc and GalNAc. Various GlcNAc derivatives with C6, both C2 and C6, as well as both C2 and C3 modifications are tolerable substrates for the newly cloned NahKs. Quite interestingly, despite of their low activities toward glucose and galactose, the activities of both NahKs are much higher for mannose and some of its C2, C4, and C6 derivatives. These NahKs are excellent catalysts for enzymatic and chemoenzymatic synthesis of carbohydrates. Full article