Intelligent skinlike materials have
recently attracted tremendous
research interests for employing in electronic skin, soft robotics,
and wearable devices. Because the traditional soft matters are restricted
in unsatisfactory mechanical performances or short-term usage, these
materials are adverse to practical applications. Here, intriguing
conductive hydrogel materials with multifunctionality (MFHs) are fabricated
by using poly(acrylic acid) (PAA), dopamine-functionalized hyaluronic
acid (DHA), and Fe3+ as ionic cross-linker. The mussel-inspired
networks with delicate combination of physical and chemical cross-linking
possess synergistic features of inherent viscoelasticity, high stretchability
(800%), and durable self-adhesiveness to various substrates. Owing
to the abundant hydrogen bonds and multiple metal coordination interactions
between Fe3+, catechol, and carboxylic groups, the matrix
reveals repeatable thermoplasticity and autonomous self-healing property
both mechanically and electrically (98% recovery in 2 s). When served
as strain sensors, the MFHs can distinctly perceive complex body motions
from tiny physiological signal (breathing) to large movements (knee
bending) as human motion detecting devices. Moreover, the MFHs were
explored as ideal material for circuit repairing, programming, and
switches constructing because of their excellent properties. Consequently,
these eco-friendly hydrogel ionotronic devices can be promising candidates
for next-generation intelligent wearable devices and human–machine
interfaces.
Photodynamic therapy (PDT) is an emerging technology for tumor treatment in which photosensitizer (PS)-mediated light irradiation reduces oxygen, producing high levels of reactive oxygen species (ROS) that can cause vascular injury and effectively kill tumor cells. However, the naturally hypoxic tumor microenvironment is the main obstacle that hinders the photodynamic response in vivo and prevents its extensive application to tumor treatment. Moreover, PDT-mediated oxygen consumption further increases tumor hypoxia, potentially causing a variety of adverse consequences, such as angiogenesis, tumor invasion, and metastasis. To overcome these limitations caused by hypoxia, multiple strategies have been investigated, including the use of oxygen carriers and reactive oxygen supply materials, the regulation of tumor microenvironments, and multimodal therapy including PDT. In this review, we summarize the latest progress in the development of strategies to relieve tumor hypoxia for improved PDT efficacy and better therapeutic effects.
Fine-tuning of gene expression is crucial for protein expression and pathway construction, but it still faces formidable challenges due to the hierarchical gene regulation at multiple levels in a context-dependent manner. In this study, we defined the optimal targeting windows for CRISPRa and CRISPRi of the dCas9-α/ω system, and demonstrated that this system could act as a single master regulator to simultaneously activate and repress the expression of different genes by designing position-specific gRNAs. The application scope of dCas9-ω was further expanded by a newly developed CRISPR-assisted
O
ligonucleotide
A
nnealing based
P
romoter
S
huffling (OAPS) strategy, which could generate a high proportion of functional promoter mutants and facilitate the construction of effective promoter libraries in microorganisms with low transformation efficiency. Combing OAPS and dCas9-ω, the influences of promoter-based transcription, molecular chaperone-assisted protein folding and protease-mediated degradation on the expression of amylase BLA in
Bacillus subtilis
were systematically evaluated, and a 260-fold enhancement of BLA production was obtained. The success of the OAPS strategy and dCas9-ω for BLA production in this study thus demonstrated that it could serve as a powerful tool kit to regulate the expression of multiple genes multi-directionally and multi-dimensionally in bacteria.
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