Polymyxins (polymyxin B and colistin) are last-line antibiotics against multidrug-resistant Gram-negative pathogens. Polymyxin resistance is increasing worldwide, with resistance most commonly regulated by two-component systems such as PmrAB and PhoPQ. This review discusses the regulatory mechanisms of PhoPQ and PmrAB in mediating polymyxin resistance, from receiving an external stimulus through to activation of genes responsible for lipid A modifications. By analyzing the reported nonsynonymous substitutions in each two-component system, we identified the domains that are critical for polymyxin resistance. Notably, for PmrB 71% of resistance-conferring nonsynonymous mutations occurred in the HAMP (present in histidine kinases, adenylate cyclases, methyl accepting proteins and phosphatase) linker and DHp (dimerization and histidine phosphotransfer) domains. These results enhance our understanding of the regulatory mechanisms underpinning polymyxin resistance and may assist with the development of new strategies to minimize resistance emergence.

Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8∼39.7 to 21.4∼32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.

Plasmonic nanostructures offer an enticing prospect in many applications, ranging from lasing to biosensing, due to their unrivaled light concentration beyond the diffraction limit. However, this promise is substantially undercut by the intrinsically high losses in metals. Here, an experimental ultra‐high‐Q plasmon resonance with a linewidth down to 2 nm (Q‐factor ≈ 350) and a resonance intensity of 51% in an ultrasmooth gold nanogroove array is reported. Such an experimental ultranarrow resonance arises from two key factors. First, a geometrical‐induced coupling between the Fabry–Pérot and Wood's anomaly modes significantly suppresses the groove array's radiative damping. Second, an ultrasmooth gold surface fabricated by template stripping minimizes its surface scattering and grain boundary scattering. Benefiting from this ultranarrow resonance, a figure of merit (FOM) of 284 and an FOM* of 617 in refraction index (RI) sensing under normally incident detection are demonstrated, the former of which is the record FOM in all reported broad‐RI‐range plasmonic RI sensors. The array is further demonstrated as a surface thickness sensor for detecting mercaptocarboxylic acids with the surface sensitivity of 0.18 nm/CH2, which suggests that the array is a promising platform for thickness detection of surface analytes and label‐free biomedical sensing.

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