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A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.  相似文献   
3.
A novel series of cleavable alkyltrimethylammonium surfactants with different hydrocarbon chain lengths (C8–16) were synthesized. A carbonate break site inserted between the polar head and the hydrocarbon chain makes these compounds hydrolyzable. The reagents used are renewable, (bio)degradable, or reusable. The hydrolysis of these cleavable surfactants will lead to the generation of fatty alcohols and choline, which is an essential biological nutrient. The surface activities in aqueous solution of the synthesized carbonates fulfill the requirement of being good surfactants. In addition, the cleavable compounds containing n-decyl and n-dodecyl chains showed similar or higher antimicrobial activities when compared to a non-cleavable analog.  相似文献   
4.
This study presents the development and characterization of PVDF-conjugated polymer nanofiber-based systems. Five different conducting polymers (CPs) were synthesized successfully and used to create the nanofiber systems. The CPs used are polyaniline (PANI), polypyrrole (PPY), polyindole (PIN), polyanthranilic acid (PANA), and polycarbazole (PCZ). Nanofiber systems were produced utilizing the Forcespinning® technique. The nanofiber systems were developed by mechanical stretching. No electrical field or post-process poling was used in the nanofiber systems. The morphology, structure, electrochemical and piezoelectric performance was characterized. All of the nanofiber PVDF/CP systems displayed higher piezoelectric performance than the fine fiber PVDF systems. The PVDF/PPY nanofiber system displays the highest piezoelectric performance of 15.56 V. The piezoelectric performance of the PVDF/CP nanofiber systems favors potential for an attractive source of energy where highly flexible membranes could be used in power actuators, sensors and portable, and wireless devices to mention some.  相似文献   
5.
Engineering the texture and nanostructure to improve the electrical conductivity of semicrystalline conjugated polymers must address the rate-limiting step for charge carrier transport. In highly face-on orientation, the charge transport between chains within a crystallite becomes rate-limiting, which is highly sensitive to the π–π stacking distance and interchain charge transfer integral. Here, face-on oriented semicrystalline poly(3,4-ethylenedioxythiophene) (PEDOT) thin films are grown via water-assisted (W-A) oxidative chemical vapor deposition (oCVD). Combining W-A with the volatile oxidant, antimony pentachloride, yields an optimized electrical conductivity of 7520  ±  240 S cm−1, a record for PEDOT thin films. Systematic control of π–π stacking distance from 3.50 Å down to 3.43 Å yields an electrical conductivity enhancement of ≈ 1140%. The highest electrical conductivity also corresponds to minimum in Urbach energy of 205 meV, indicating superior morphological order. The figure of merit for transparent conductors, σdcop, reaches a maximum value of 94, which is 1.9 × and 6.7 × higher than oCVD PEDOT grown without W-A and utilizing vanadium oxytrichloride and iron chloride oxidizing agents, respectively. The W-A oCVD is single-step all-dry process and provides conformal coverage, allowing direct growth on mechanical flexible, rough, and structured surfaces without the need for complex and costly transfer steps.  相似文献   
6.
<正>自2002年以合伙人的身份加入B+H以来,Karen见证了亚洲经济的高速增长时期,并带领B+H在亚洲的发展。过去十几年间,B+H稳步增长,相继在上海、胡志明市、新加坡以及香港开设办公室,目前B+H在亚洲拥有将近300名员工,服务于亚洲乃至全世界范围内一些高知名度的客户。问题1:您能给我们简单介绍一下B+H的历史以及B+H在亚洲地区的演变和发展轨迹吗?  相似文献   
7.
To make personalised medicine a reality, there is a significant need for cost-effective methods that enable the rapid selection of optimal nutrient intake and/or disease treatment with a minimum of side effects. In this perspective, we briefly discuss the potential of merging the advances of microfluidic devices, organoid structures and advanced analytical methods to progress towards a personalised in vitro platform for health and wellbeing. © 2019 Society of Chemical Industry  相似文献   
8.
Agave tequilana bagasse is a suitable lignocellulosic residue for energy production. However, the presence of lignin and the heterogeneous structure of hemicellulose may hinder the availability of polysaccharides. In this work, the pretreatment of A. tequilana bagasse with alkaline hydrogen peroxide (AHP) followed by enzymatic saccharification with hemicellulases and cellulases was assessed for the removal of lignin and extraction of fermentable sugars, respectively. Results of the AHP pretreatment indicated that it is possible to attain up to 97% delignification and recover 88% of cellulose and hemicellulose after only 1.5 h of treatment. Regarding the saccharification process, the total sugar yield and productivity were both increased by 2-fold using an enzymatic mixture (cellulases + hemicellulases) compared to single enzyme hydrolysis (cellulases), evidencing synergism. Further evaluation of the hydrolyzates as substrate for hydrogen and methane production, resulted in yields 1.5 and 3.6-times (215.14 ± 13 L H2 and 393.4 ± 13 L CH4 per kg bagasse, respectively) superior to those obtained with hydrolyzates of non-pretreated bagasse processed with a single enzyme. Overall, using AHP pretreatment and subsequent hydrolysis with enzymatic mixtures improves the saccharification of A. tequilana bagasse enhancing the production of hydrogen and methane.  相似文献   
9.
Greenhouses in northern climates require a large amount of supplemental heating for growing crops in winter seasons, so energy‐efficient design of greenhouses based on local climate is important to minimize the heating demand. In this study, greenhouse design parameters including shape, orientation, the angle of the roof, and width of the span have been studied for the conceptual design of conventional greenhouses for Canadian Prairies using a heating simulation model. Five different shapes of greenhouses including even‐span, uneven‐span, modified arch, vinery, and quonset shape have been selected for the study. The simulation results proved that the uneven‐span gable roof shape receives the highest solar radiation, whereas the quonset shape receives the lowest solar radiation. However, the quonset shape greenhouse requires about 7.6% less annual heating as compared to the gable roof greenhouse, but the quonset would not be adopted as multispan greenhouses. Therefore, the gable roof greenhouse is considered as energy efficient for the multispan gutter connected greenhouses whereas quonset shape as a free‐standing single‐span greenhouses. In high northern latitudes, the greenhouse with east‐west orientation is more energy efficient from heating and cooling point of view when the length‐width ratio of the greenhouse is more than 1. The heating energy saving potential of the large span width in single‐span greenhouses is relatively higher as compared to the multispan greenhouses.  相似文献   
10.
The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.  相似文献   
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