Specific inhibitors of human pancreatic alpha-amylase (HPA) have potential as oral agents for the control of blood glucose levels in the treatment of diabetes and obesity. In a search for novel inhibitors, a library of 30 000 crude biological extracts of terrestrial and marine origin has been screened. A number of inhibitory extracts were identified, of which the most potent was subjected to bioassay-guided purification. A family of three glycosylated acyl flavonols, montbretins A-C, was thereby identified and characterized as competitive amylase inhibitors, with K(i) values ranging from 8.1-6100 nM. Competitive inhibition by myricetin, which corresponds to the flavone core, and noncompetitive inhibition by a second fragment, ethyl caffeiate, suggest a binding mode for these inhibitors.

Ample evidence suggests that almost all polypeptides can either adopt a native structure (folded or intrinsically disordered) or form misfolded amyloid fibrils. Soluble protein oligomers exist as an intermediate between these two states, and their cytotoxicity has been implicated in the pathology of multiple human diseases. However, the mechanism by which soluble protein oligomers develop into insoluble amyloid fibrils is not clear, and investigation of this important issue is hindered by the unavailability of stable protein oligomers. Here, we have obtained stabilized protein oligomers generated from common native proteins. These oligomers exert strong cytotoxicity and display a common conformational structure shared with known protein oligomers. They are soluble and remain stable in solution. Intriguingly, the stabilized protein oligomers interact preferentially with both nucleic acids and glycosaminoglycans (GAG), which facilitates their rapid conversion into insoluble amyloid. Concomitantly, binding with nucleic acids or GAG strongly diminished the cytotoxicity of the protein oligomers. EGCG, a small molecule that was previously shown to directly bind to protein oligomers, effectively inhibits the conversion to amyloid. These results indicate that stabilized oligomers of common proteins display characteristics similar to those of disease-associated protein oligomers and represent immediate precursors of less toxic amyloid fibrils. Amyloid conversion is potently expedited by certain physiological factors, such as nucleic acids and GAGs. These findings concur with reports of cofactor involvement with disease-associated amyloid and shed light on potential means to interfere with the pathogenic properties of misfolded proteins.

Photodynamic therapy (PDT) functions when the light-excited photosensitizers transfer energy to oxygen molecules ( 3 O 2 ) to produce cytotoxic singlet oxygen ( 1 O 2 ) that can effectively kill cells or bacteria. However, the PDT efficacy is often reduced by the limited availability of 3 O 2 surrounding the photosensitizer and extremely short diffusion range of the photoactivated 1 O 2 . Herein, an enzymatic micromotor based on hollow mesoporous SiO 2 (mSiO 2 ) microspheres is constructed as a mobile and highly efficient photosensitizer platform. Carboxylated magnetic nanoparticles are connected with both hollow spheres and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin molecules through covalent linkage between amino and carboxylic groups within a one-step reaction. Due to the intrinsic asymmetry of the mSiO 2 spheres, the micromotors can be propelled by ionic diffusiophoresis induced by the enzymatic decomposition of urea. Via numerical simulation, the self-propulsion mechanism is clarified and the movement direction is identified. By virtue of active self-propulsion, the current system can overcome the long-standing shortcomings of PDT and significantly enhance the PDT efficacy by improving the accessibility of the photosensitizer to 3 O 2 and enlarging the diffusing range of 1 O 2 . Therefore, by proposing a new solution to the bottleneck problems of PDT, this work provides insightful perspectives to the biomedical application of multifunctional micro/nanomotors. applications, including targeted drug delivery, mini-surgery, biochemical sensing, and diagnostics. [13][14][15] In particular, MNMs as active carriers with the capability of cargo loading and controllable motion have great potentials for effective delivery of different types of cargos. [15] So far, researchers have also explored stimuli-responsive materials, [16][17][18][19] biomimetic materials, [20][21][22] and micro-organisms functionalized with nanomaterials [23] as MNMs to precisely transport cargos of drugs, [16,20,23,24] proteins, [18,22,25] and genes [19] in vitro and/or in vivo. Compared with traditional passive delivery, MNMs can perform tasks such as controlled navigation, rapid transportation, and active delivery of payloads to disease sites, and thus have paved way for on demand biomedical cargo transportation. [15] Inspired by these achievements, we envision that self-propelled MNMs can serve as a mobile photosensitizer platform to improve the availability of 3 O 2 as well as the diffusion range of 1 O 2 , which can consequently achieve highly efficient PDT process.

Silver microflower arrays constructed by upright nanoplates and attached nanoparticles were fabricated inside a microfluidic channel, thus a robust catalytic microreactor for allowing in situ SERS monitoring was proposed. On-chip catalytic reduction shows that the silver microflowers have high catalytic activity and SERS enhancement.