Notes

Tat-thioredoxin 1 lowers inflammation by curbing pro-inflammatory cytokines and also modulating MAPK signaling.
Implantable and wearable materials, which are usually used in/on a biological body, are mostly needed with biomimetic self-healing function. To enable repeatable large-wound self-healing and volume/structure recovery, we verified a proof-of-concept approach in this work. We design a polymer hydrogel that combines temperature responsiveness with an intrinsic self-healing ability through host-guest orthogonal self-assembly between two types of poly(N-isopropylacrylamide) (PNIPAM) oligomers. The result is thermosensitive, capable of fast self-repair of microcracks based on reversible host-guest assembly. More importantly, when a large open wound appears, the hydrogel can first close the wound via volume swelling and then completely self-repair the damage in terms of intrinsic self-healing. Meanwhile, its original volume can be easily recovered by subsequent contraction. As demonstrated by the experimental data, such millimeter-level wound self-healing and volume recovery can be repeatedly carried out in response to the short-term cooling stimulus. With low cytotoxicity and good biocompatibility, moreover, this highly intelligent hydrogel is greatly promising for practical large-wound self-healing in wound dressing, electronic skins, wearable biosensors, and humanoid robotics, which can tolerate large-scale human motions.Binary photoresponse characteristics can help realize optical signal processing and logic operations. HPPE supplier UV photodetectors (PDs) with SnSx nanoflakes and TiO2 nanorod arrays (NRs) show a novel binary photoswitching behavior (change in current from positive to negative) by manipulating the light wavelength without an external power source, utilizing the interfacial recombination of the photogenerated carriers in the type-I SnSx/TiO2 heterojunctions. The enhanced responsivity (R*), detectivity (D*), and fast photoresponse time for self-powered SnSx/TiO2PDs can be achieved by adjusting the phase ratio of SnS and SnS2 nanoflakes. The binary photoswitching in the self-powered UV PDs can be applied in the encrypted optical signal processing and imaging in some special conditions without external bias.Targeting protein degradation with Proteolysis-Targeting Chimeras (PROTACs) is an area of great current interest in drug discovery. Nevertheless, although the high effectiveness of PROTACs against a wide variety of targets has been established, most degraders reported to date display limited intrinsic tissue selectivity and do not discriminate between cells of different types. Here, we describe a strategy for selective protein degradation in a specific cell type. We report the design and synthesis of a trastuzumab-PROTAC conjugate (Ab-PROTAC 3) in which E3 ligase-directed degrader activity is caged with an antibody linker which can be hydrolyzed following antibody-PROTAC internalization, releasing the active PROTAC and inducing catalytic protein degradation. We show that 3 selectively targets bromodomain-containing protein 4 (BRD4) for degradation only in HER2 positive breast cancer cell lines, while sparing HER2 negative cells. Using live cell confocal microscopy, we show internalization and lysosomal trafficking of the conjugate specifically in HER2 positive cells, leading to the release of active PROTAC in quantities sufficient to induce potent BRD4 degradation. These studies demonstrate proof-of-concept for tissue-specific BRD4 degradation, overcoming limitations of PROTAC selectivity, with significant potential for application to novel targets.A new class of biosensing transducer based on alternating-current electroluminescent (ACEL) display is demonstrated. Unlike conventional ACEL displays where they have been rigidly used in flexible screens and advertising applications, here, the display is integrated with immunoassay and functioned as an optical transducer. Taking advantage of the reversed ACEL architecture, the display can be simply fabricated on an unconventional paper material without requiring the transparent indium tin oxide (ITO) electrode. The sensing mechanism relies on the promoted electronic conduction from the immunocomplex formation between immobilized antibody, antigen, and nanoparticle labeled antibody. As a result, the electroluminescence could be triggered off instantaneously. To demonstrate the device effectiveness, C-reactive protein (CRP), a particular biomarker of an inflammatory process and cardiovascular disease, is chosen as a model analyte in this work. Additionally, the applicability of the proposed platform is proved efficacious in human serums, showing negligible interference from nontargeting proteins. The sensing display is also capable of performing multiple assays (up to 8) within a single device. This bio-optoelectronic device represents a straightforward yet highly sensitive approach. This ACEL transducer is believed to explore new possibilities for biosensing and exploit in point-of-care testing.The role of additives in facilitating the growth of conventional semiconducting thin films is well-established. Apparently, their presence is also decisive in the growth of two-dimensional transition metal dichalcogenides (TMDs), yet their role remains ambiguous. In this work, we show that the use of sodium bromide enables synthesis of TMD monolayers via a surfactant-mediated growth mechanism, without introducing liquefaction of metal oxide precursors. We discovered that sodium ions provided by sodium bromide chemically passivate edges of growing molybdenum disulfide crystals, relaxing in-plane strains to suppress 3D islanding and promote monolayer growth. To exploit this growth model, molybdenum disulfide monolayers were directly grown into desired patterns using predeposited sodium bromide as a removable template. The surfactant-mediated growth not only extends the families of metal oxide precursors but also offers a way for lithography-free patterning of TMD monolayers on various surfaces to facilitate fabrication of atomically thin electronic devices.We have previously identified the natural product obtusaquinone (OBT) as a potent antineoplastic agent with promising in vivo activity in glioblastoma and breast cancer through the activation of oxidative stress; however, the molecular properties of this compound remained elusive. We used a multidisciplinary approach comprising medicinal chemistry, quantitative mass spectrometry-based proteomics, functional studies in cancer cells, and pharmacokinetic analysis, as well as mouse xenograft models to develop and validate novel OBT analogs and characterize the molecular mechanism of action of OBT. We show here that OBT binds to cysteine residues with a particular affinity to cysteine-rich Keap1, a member of the CUL3 ubiquitin ligase complex. This binding promotes an overall stress response and results in ubiquitination and proteasomal degradation of Keap1 and downstream activation of the Nrf2 pathway. Using positron emission tomography (PET) imaging with the PET-tracer 2-[18F]fluoro-2-deoxy-d-glucose (FDG), we confirm that OBT is able to penetrate the brain and functionally target brain tumors.
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