Moving ships and other objects drifting on water often impact a bridge' s pile foundations. The mechanical model of the piles-bridge structure under horizontal forcing was established, and a time-domain approach b...Moving ships and other objects drifting on water often impact a bridge' s pile foundations. The mechanical model of the piles-bridge structure under horizontal forcing was established, and a time-domain approach based on Finite-difference Method was developed for analyzing the dynamic response of the piles-bridge structure. For a single pile, good agreement between two computed results validated the present approach.The slenderness ratio of the pile, the pile-soil stiffness ratio and the type of the structure influence the dynamic response of the piles-bridge structure. The computed results showed that the stiffness of the structure determines the dynamic response of the piles-bridge structure under horizontal forcing.展开更多
Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fet...Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.展开更多
We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DN...We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3＇-end and an extension sequence at the 5＇-end with 5-carboxytetramethylrhodamine （TAMRA） label （denoted as strand A）. The other （strand ｜）, being competent to work on the formation of i-motif structure, contained four stretches of the cytosine （C） rich domain and was labeled with a Black Hole Quencher 2 （BHQ2） at the 3＇-end. At neutral or slightly alkaline pH, strand ｜ was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe （I-AAP）. Because of proximity- induced energy transfer, the I-AAP was in a ＂signal off＇ state. The slightly acidic pH enforced the strand I to form an intramo- lecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.展开更多
The stimuli-responsive nanomaterials are gaining more and more interest in the biological field,including cell imaging and biosensing etc. Nanomaterials in response to the bio-relevant stimuli(i.e., p H, enzymes and o...The stimuli-responsive nanomaterials are gaining more and more interest in the biological field,including cell imaging and biosensing etc. Nanomaterials in response to the bio-relevant stimuli(i.e., p H, enzymes and other bioactive molecules) can be utilized to enhance imaging(i.e., optical imaging, MRI, and multi-mode imaging) sensitivity via disease site-specific delivery and controlled release, which helps to diagnose cancer at an early stage or to monitor progression during treatment. In the triggered responsive process, smart nanomaterials undergo changes in physiochemical properties that can cause cytotoxicity or influence on cell functions due to the interactions between nanomaterials and cells. In order to promote the design and fabrication of effective platforms for therapeutics and diagnostics, special attention should be paid to these effects. By taking the advantages of intracellular stimuli, the controlled self-assembly in living cells can be achieved, which has been used for various in situ detections and insights into biological self-assembly. In this review, the recent advances in cell imaging, cytotoxicity and self-assembly of intracellular stimuli-responsive nanomaterials are summarized. Some principles for the further design and applications of intracellular stimuli-responsive nanomaterials and future perspectives are discussed.展开更多
文摘Moving ships and other objects drifting on water often impact a bridge' s pile foundations. The mechanical model of the piles-bridge structure under horizontal forcing was established, and a time-domain approach based on Finite-difference Method was developed for analyzing the dynamic response of the piles-bridge structure. For a single pile, good agreement between two computed results validated the present approach.The slenderness ratio of the pile, the pile-soil stiffness ratio and the type of the structure influence the dynamic response of the piles-bridge structure. The computed results showed that the stiffness of the structure determines the dynamic response of the piles-bridge structure under horizontal forcing.
文摘Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.
基金supported by the Key Project of National Natural Science Foundation of China (21175039, 21322509, 21305035, 21190044, 21221003, 21305038, 2015JJ3044)
文摘We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3＇-end and an extension sequence at the 5＇-end with 5-carboxytetramethylrhodamine （TAMRA） label （denoted as strand A）. The other （strand ｜）, being competent to work on the formation of i-motif structure, contained four stretches of the cytosine （C） rich domain and was labeled with a Black Hole Quencher 2 （BHQ2） at the 3＇-end. At neutral or slightly alkaline pH, strand ｜ was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe （I-AAP）. Because of proximity- induced energy transfer, the I-AAP was in a ＂signal off＇ state. The slightly acidic pH enforced the strand I to form an intramo- lecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.
基金supported by the National Natural Science Foundation of China(51120135001)Ph.D.Programs Foundation of Ministry of Education of China(20110101130005)
文摘The stimuli-responsive nanomaterials are gaining more and more interest in the biological field,including cell imaging and biosensing etc. Nanomaterials in response to the bio-relevant stimuli(i.e., p H, enzymes and other bioactive molecules) can be utilized to enhance imaging(i.e., optical imaging, MRI, and multi-mode imaging) sensitivity via disease site-specific delivery and controlled release, which helps to diagnose cancer at an early stage or to monitor progression during treatment. In the triggered responsive process, smart nanomaterials undergo changes in physiochemical properties that can cause cytotoxicity or influence on cell functions due to the interactions between nanomaterials and cells. In order to promote the design and fabrication of effective platforms for therapeutics and diagnostics, special attention should be paid to these effects. By taking the advantages of intracellular stimuli, the controlled self-assembly in living cells can be achieved, which has been used for various in situ detections and insights into biological self-assembly. In this review, the recent advances in cell imaging, cytotoxicity and self-assembly of intracellular stimuli-responsive nanomaterials are summarized. Some principles for the further design and applications of intracellular stimuli-responsive nanomaterials and future perspectives are discussed.
