Aptamers
and antibodies, as molecular recognition probes, play
critical roles in cancer diagnosis and therapy. However, their recognition
ability is based on target overexpression in disease cells, not target
exclusivity, which can cause on-target off-tumor effects. To address
the limitation, we herein report a novel strategy to develop a conditional
aptamer conjugate which recognizes its cell surface target, but only
after selective activation, as determined by characteristics of the
disease microenvironment, which, in our model, involve tumor hypoxia.
This conditional aptamer is the result of conjugating the aptamer
with PEG5000-azobenzene-NHS, which is responsive to hypoxia,
here acting as a caging moiety of conditional recognition. More specifically,
the caging moiety is unresponsive in the intact conjugate and prevents
target recognition. However, in the presence of sodium dithionite
or hypoxia (<0.1% O2) or in the tumor microenvironment,
the caging moiety responds by allowing conditional recognition of
the cell-surface target, thereby reducing the chance of on-target
off-tumor effects. It is also confirmed that the strategy can be used
for developing a conditional antibody. Therefore, this study demonstrates
an efficient strategy by which to develop aptamer/antibody-based diagnostic
probes and therapeutic drugs for cancers with a unique hypoxic microenvironment.
An upconverting covalent organic framework nanoplatform is designed for the first time for the near-infrared activated in situ self-reporting of photodynamic therapy in vivo.
Polytherapy( or drug combination cancer therapy (DCCT)), targeting multiple mechanisms associated with tumor proliferation, can efficiently maximizet herapeutic efficacy,d ecrease drug dosage,a nd reduce drug resistance. However,most DCCT strategies cannot coordinate the specific delivery of adrug combination in an accurately tuned ratio into cancer cells.T oa ddress these limitations,t he present work reports the engineering of circular bivalent aptamer-drug conjugates (cb-ApDCs). The cb-ApDCs exhibit high stability, specific recognition, excellent cellular uptake,a nd esterasetriggered release.F urthermore,t he drug ratios in cb-ApDCs can be tuned for an enhanced synergistic effect without the need for complex chemistry.T herefore,c b-ApDCs provide apromising platform for the development of DCCT strategies for different drug combinations and ratios.
Five diets that contained fresh squid meat as the basic constituent and were supplemented with different amounts of highly unsaturated fatty acids (HUFA) and astaxanthin were fed to pond‐reared Penaeus monodon broodstock. Diet A was sole squid meat. Diets B and C were supplemented with astaxanthin 50 and 100 mg kg−1 respectively. Diets D and E were supplemented with HUFA 5 and 10 g kg−1 and astaxanthin 50 mg kg−1 respectively. The result showed that the group fed diet E had the best reproductive performance in all experimental groups. It had a higher proportion of spawns (71.5%), spawning rate (0.047), a shorter latency period (7.7±0.3 d), higher absolute fecundity (× 103) (361.6±5.5) and egg production/female (× 103) (597.0±18.0) than all the other experimental groups. The fatty acid composition in broodstock diets strongly affected the tissue and fecundity of broodstock. Good correlations between the content of 20:4n‐6 in eggs and the fecundity (r2=0.6109) and egg production (r2=0.9876) of broodstock were found. On the other hand, 22:6n‐3 and DHA/EPA ratio was negatively correlated with the fecundity of broodstock (r2=0.5362, 0.8702 respectively). The result also showed that the balance between n‐3 and n‐6 fatty acid families, total polyunsaturated fatty acids and total saturated fatty acid and 20:5n‐3 (EPA) and 22:6n‐3 (DHA) may play vital roles in maturation and reproductive performance of P. monodon broodstock.
Background
The
Bemisia tabaci
is a major leaf feeding insect pest to pepper (
Capsicum annuum
), causing serious damage to pepper growth and yield. It is particularly important to study the mechanism of pepper resistance to
B. tabaci
, and to breed and promote the varieties of pepper resistant to
B. tabaci
. However, very limited molecular mechanism is available about how plants perceive and defend themselves from the destructive pest. Proteome technologies have provided an idea method for studying plant physiological processes in response to
B. tabaci
.
Results
Here, a highly resistant genotype and a highly susceptible genotype were exposed to
B. tabaci
feeding for 48 h to explore the defense mechanisms of pepper resistance to
B. tabaci
. The proteomic differences between both genotypes were compared using isobaric tag for relative and absolute quantification (iTRAQ). The quantitative data were validated by parallel reaction monitoring (PRM). The results showed that 37 differential abundance proteins (DAPs) were identified in the RG (resistant genotype), while 17 DAPs were identified in the SG (susceptible genotype) at 48 h after
B. tabaci
feeding. 77 DAPs were identified when comparing RG with SG without feeding. The DAP functions were determined for the classification of the pathways, mainly involved in redox regulation, stress response, protein metabolism, lipid metabolism and carbon metabolism. Some candidate DAPs are closely related to
B. tabaci
resistance such as annexin D4-like (ANN4), calreticulin-3 (CRT3), heme-binding protein 2-like (HBP1), acidic endochitinase pcht28-like (PR3) and lipoxygenase 2 (LOX2).
Conclusions
Taken together, this study indicates complex resistance-related events in
B. tabaci
interaction, provides novel insights into the molecular mechanism underlying the response of plant to
B. tabaci
, and identifies some candidate proteins against
B. tabaci
attack.
Electronic supplementary material
The online version of this article (10.1186/s12870-019-1849-0) contains supplementary material, which is available to authorized users.
Heat shock proteins (Hsps) are a class of highly conserved proteins produced in virtually all living organisms from bacteria to humans. Hsp60 and Hsp10, the most important mitochondrial chaperones, participate in environmental stress responses. In this study, the full-length complementary DNAs (cDNAs) of Hsp60 (PmHsp60) and Hsp10 (PmHsp10) were cloned from Penaeus monodon. Sequence analysis showed that PmHsp60 and PmHsp10 encoded polypeptides of 578 and 102 amino acids, respectively. The expression profiles of PmHsp60 and PmHsp10 were detected in the gills and hepatopancreas of the shrimps under pH challenge, osmotic stress, and heavy metal exposure, and results suggested that PmHsp60 and PmHsp10 were involved in the responses to these stimuli. ATPase and chaperone activity assay indicated that PmHsp60 could slow down protein denaturation and that Hsp60/Hsp10 may be combined to produce a chaperone complex with effective chaperone and ATPase activities. Overall, this study provides useful information to help further understand the functional mechanisms of the environmental stress responses of Hsp60 and Hsp10 in shrimp.
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