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18 MPa, and ε = 860%). The combination of ultra-stiffness, toughness, and stretchability in hydrogels is successfully achieved through leveraging the hierarchically cross-linked network based on hydrogen bonding and coordination bonding. Moreover, utilizing the wide distribution of bonding strength of coordination interaction, the mechanical properties of triple-crosslinked hydrogels can be manipulated by using different kinds of catechol-metal coordination.Rhodium(iii)-catalyzed C-H acylation of heteroarenes has been realized using cyclobutenones as an acylating reagent. This coupling proceeded via integration of C-H activation of heteroarenes and C-C cleavage of cyclobutenones. The reaction features excellent regio/chemoselectivity leading to versatile chalcones with exclusive E-selectivity.Metal-organic frameworks (MOFs) are an emerging class of molecular crystalline materials built from metal ions or clusters bridged by organic linkers. By taking advantage of their synthetic tunability and structural regularity, MOFs can hierarchically integrate nanoparticles and/or biomolecules into a single framework to enable multifunctions. The MOF-protected heterostructures not only enhance the catalytic capacity of nanoparticle components but also retain the biological activity of biomolecules in an intracellular microenvironment. Therefore, the multifunctional MOF heterostructures have great advantages over single components in cancer therapy. In this review, we comprehensively summarize the general principle of the design and functional modulation of nanoscaled MOF heterostructures, and biomedical applications in enhanced therapy within the last five years. The functions of MOF heterostructures with a controlled size can be regulated by designing various functional ligands and in situ growth/postmodification of nanoparticles and/or biomolecules. The advances in the application of multifunctional MOF heterostructures are also explored for enhanced cancer therapies involving photodynamic therapy, photothermal therapy, chemotherapy, radiotherapy, immunotherapy, and theranostics. The remaining challenges and future opportunities in this field, in terms of precisely localized assembly, maximizing composite properties, and processing new techniques, are also presented. The introduction of multiple components into one crystalline MOF provides a promising approach to design all-in-one theranostics in clinical treatments.The highly sensitive and reliable detection, imaging, and monitoring of changes of intracellular caspase-3 are critical for understanding the cell apoptosis and studying the progression of caspase-3-related cervical cancer. Herein, we present a novel surface-enhanced Raman scattering (SERS) probe for the detection of caspase-3 during cervical cancer cell apoptosis, composed of Au nanoboxes modified with Nile blue A as a Raman reporter and a caspase-3-specified peptide as a molecular cross-linker. In the presence of caspase-3, the substrate peptides can be cleaved and the changed surface charge of the Au nanoboxes results in the Au nanoboxes-NBA-peptide assembling to form aggregates and a great enhancement of SERS signal. The finite-difference time-domain simulation showed that hot spots mainly located in the nanogaps of the aggregated Au nanoboxes, which in theory proved the rationality of this signal amplification method. The SERS probes exhibited excellent reproducibility and selectivity toward caspase-3. A detection limit of 0.127 fM was obtained for caspase-3, with a dynamic range from 1 fM to 1 nM. MTT assay demonstrated that the probes had no obvious cytotoxicity within a certain concentration range. HeLa cells were treated with doxorubicin to induce long-term apoptosis. Upon cellular uptake of these probes, the spatiotemporal dynamics of caspase-3 in apoptotic cells could be real-time monitored using SERS. The activity of caspase-3 increased with the prolongation of apoptosis time. G150 The SERS results were in accordance with that of western blotting assay. This kind of probe can offer great potential for the determination of enzymatic activities in the physiological processes of cells.Obesity has a serious effect on human health. It relates to metabolic syndrome, including the associated disorders such as type 2 diabetes, heart disease, stroke and hyperemia. The peroxisome proliferator-activated receptors (PPARs) are important receptors to control fat metabolism in the human body. Because of the safety concerns of synthetic drugs targeting PPARs, ligands from natural sources have drawn interest. Earlier, we have found high PPAR activities in extracts from Agaricus bisporus (white button mushroom, WBM). WBM contains a wide range of candidate compounds which could be agonists of PPARs. To identify which compounds are responsible for PPAR activation by WBM extracts, we used fractionation coupled to effect-directed analysis with reporter gene assays specific for all three PPARs for purification and LC/MS-TOF and NMR for compound identification in purified active fractions. Surprisingly, we identified the relatively common dietary fatty acid, linoleic acid, as the main ligand of PPARs in WBM. Possibly, the relatively low levels of linoleic acid in WBM are sufficient and instrumental in inducing its anti-obesogenic effects, avoiding high energy intake and negative health effects associated with high levels of linoleic acid consumption. However, it could not be excluded that a minor relatively potent compound contributes towards PPAR activation, while the anti-obesity effects of WBM may be further enhanced by receptor expression modulating compounds or compounds with completely PPAR unrelated modes of action.Recent experiments have reported anomalously large screening lengths of interactions between charged surfaces confining concentrated electrolytes and ionic liquids. Termed underscreening, this effect was ascribed to bulk properties of dense ionic systems. Herein, we study bulk ionic screening with extremely large-scale molecular dynamics simulations, allowing us to assess the range of distances relevant to the experiments. Our results yield two screening lengths satisfying distinct scaling relations. However, with an accuracy of 10-5kBT in interionic potentials of mean force, we find no signs of underscreening, suggesting that other than bulk effects might be at play in the experiments.
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