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901.
Two new compounds, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid (1) and 3α-hydroxylup-20(29)-ene-23,28-dioic acid 28-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester (2), and eight known lupane-type triterpenoids (3-10), were isolated from steamed leaves of Acanthopanax koreanum. Chemical structures were determined using a combination of spectroscopic analyses and chemical reactivity. Compounds 1-10 were evaluated for their inhibitory activities on lipopolysaccharide (LPS)-stimulated interleukin (IL)-12 production in bone marrow-derived dendritic cells (BMDCs). Compound 1 exhibited inhibitory activity with IC(50) value of 26.5 μM on IL-12 production, compared with IC(50) value of 29.6 μM for the positive control. Compound 1 also showed significant suppression of LPS-stimulated IL-6 and tumor necrosis factor-alpha (TNF-α) production. 相似文献
902.
Chun-Ho Park Kwangwoo Chun Bo-Young Joe Ji-Seon Park Young-Chul Kim Ji-Soo Choi Dong-Kyu Ryu Seong-Ho Koh Goang Won Cho Seung Hyun Kim Myung-Hwa Kim 《Bioorganic & medicinal chemistry letters》2010,20(7):2250-2253
Highly potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1,2-dihydro-4H-thiopyrano[3,4-c]quinolin-5(6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC50 = 42 nM, ED50 = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo. 相似文献
903.
Sung Yun Cho Sun-Young Han Jae Du Ha Jae Wook Ryu Chong Ock Lee Heejung Jung Nam Sook Kang Hyoung Rae Kim Jong Sung Koh Jongkook Lee 《Bioorganic & medicinal chemistry letters》2010,20(14):4223-4227
We report the synthesis and biological evaluation of aminopyridines substituted with benzoxazole. The SAR of the aminopyridines was explored to improve the inhibitory activity against c-Met and to decrease hERG affinity. These studies led to the discovery of amide 24 which showed good c-Met inhibitory potency, low affinity to hERG and favorable pharmacokinetic properties in rats. 相似文献
904.
Backpack load carriage increases ground reaction forces and increases the stiffness in the upper extremity that can cause transmission of higher amount of forces from the lower extremity to the head. This study investigated the effect of load carriage and placement of load on the back on the shock transmission mechanisms amongst children. Fifteen primary school boys with mean age 10.01 (±1.31) years, mean height 136.40 (±10.08) cm and mean mass 31.83 (±7.13) kg completed the study. Subjects carried 10%, 15% and 20% bodyweight (BW) loads on two locations on the back, namely upper and lower. Results showed a significant reduction in pelvic and trunk rotation in the transverse plane and an increase in the upper body stiffness for loads exceeding 15% of BW. The lower limb results showed a reduction in the first peak force and cadence and a significant change in the walking velocity and time to the first peak force for 20% load. No significant differences were found for the load configuration but the upper configuration showed slightly higher shock transmission. The changes in the lower limb dynamics indicated that there are locomotion mechanisms in place amongst children to modulate shock transmission to the head. 相似文献
905.
Kyoung Jin Yeon-Ja Koh Seong Kyu Ahn Joonghee Cho Junghwan Lim Jaeyong Song Jinyoung Lee Young Woo Gong Mun Ju Kwon Hyung Wook Kwon Young Yil Bahk Tong-Soo Kim 《The Korean journal of parasitology》2021,59(3):281
This study aimed to characterize the seasonal abundance of hard ticks that transmit severe fever with thrombocytopenia syndrome virus from April to November 2019 and 2020 on Ganghwa-do, Incheon Metropolitan City, Korea. The ticks were collected at grassland, grave site, copse and mountain road using a collection trap method. The ixodid hard ticks comprising three species (Haemaphysalis longicornis, H. flava, and Ixodes nipponensis) collected were 6,622 in 2019 and 3,811 in 2020. H. longicornis was the most frequent (97.9% in 2019 and 96.0% in 2020), followed by H. flava (2.0% and 3.0% in 2019 and 2020, respectively) and I. nipponensis (less than 0.1%). Our study demonstrated that seasonal patterns of the tick populations examined for two years were totally unsimilar. The hard ticks tested using RT-qPCR were all negative for severe fever with thrombocytopenia syndrome virus. 相似文献
906.
In vitro experimental models pertaining to human cells are considered essential for most biological experiments, such as drug development and analysis of disease mechanisms, because of their genetic consistency and ease for detailed and long-term analysis. Recent development of organoid cultures, such as intestine, liver, and kidney cultures, greatly promotes the potential of in vitro experiments. However, conventional culture methods that use manual pipetting have limitations in regenerating complex biosystems. Our body autonomously organizes cells to form a specific tissue shape, and the self-organization process occurs in an extremely systematic manner. In order to emulate this sophisticated process in vitro; first, methodologies for cell culture and organization of in vitro systems need to be updated; second, understanding the self-organizing system is a crucial issue. In this review, recent advancements in engineering technologies to control the microenvironment during cell culture are introduced. Both static and dynamic control have been developed for decades in engineering fields, and the means by which such technologies can help to elucidate and design a biosystem is discussed. 相似文献
907.
908.
Alan Koh Marjorie J. Gibbon Marc W. Van der Kamp Christopher R. Pudney Susanne Gebhard 《Molecular microbiology》2021,115(1):157-174
Bacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic in Bacillus subtilis enabling the cell to directly monitor its need for detoxification. This cost‐effective strategy is achieved via a two‐component regulatory system (BceRS) working in a sensory complex with an ABC‐transporter (BceAB), together acting as a flux‐sensor where signaling is proportional to transport activity. How this is realized at the molecular level has remained unknown. Using experimentation and computation we here show that the histidine kinase is activated by piston‐like displacements in the membrane, which are converted to helical rotations in the catalytic core via an intervening HAMP‐like domain. Intriguingly, the transporter was not only required for kinase activation, but also to actively maintain the kinase in its inactive state in the absence of antibiotics. Such coupling of kinase activity to that of the transporter ensures the complete control required for transport flux‐dependent signaling. Moreover, we show that the transporter likely conserves energy by signaling with sub‐maximal sensitivity. These results provide the first mechanistic insights into transport flux‐dependent signaling, a unique strategy for energy‐efficient decision making. 相似文献
909.
Background
Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis.Methods
We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models.Results
There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001).Discussion and Conclusion
A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence. 相似文献910.
Stefan Reuscher Masahito Akiyama Chiharu Mori Koh Aoki Daisuke Shibata Katsuhiro Shiratake 《PloS one》2013,8(11)
The family of aquaporins, also called water channels or major intrinsic proteins, is characterized by six transmembrane domains that together facilitate the transport of water and a variety of low molecular weight solutes. They are found in all domains of life, but show their highest diversity in plants. Numerous studies identified aquaporins as important targets for improving plant performance under drought stress. The phylogeny of aquaporins is well established based on model species like Arabidopsis thaliana, which can be used as a template to investigate aquaporins in other species. In this study we comprehensively identified aquaporin encoding genes in tomato (Solanum lycopersicum), which is an important vegetable crop and also serves as a model for fleshy fruit development. We found 47 aquaporin genes in the tomato genome and analyzed their structural features. Based on a phylogenetic analysis of the deduced amino acid sequences the aquaporin genes were assigned to five subfamilies (PIPs, TIPs, NIPs, SIPs and XIPs) and their substrate specificity was assessed on the basis of key amino acid residues. As ESTs were available for 32 genes, expression of these genes was analyzed in 13 different tissues and developmental stages of tomato. We detected tissue-specific and development-specific expression of tomato aquaporin genes, which is a first step towards revealing the contribution of aquaporins to water and solute transport in leaves and during fruit development. 相似文献