[Study on the Wavelength Selection Based on VIP Analysis in Noninvasive Measurement of Blood Components].

Selection of independent variable is a hotspot in the field of quantitative spectral analysis. Efficient and easy-to-use method for wavelength selection can not only reduce the computation and improve the accuracy of analysis, but also can reduce dependency on the spectral resolution of instruments and cut cost. Wavelength selection is also an important part of the research about noninvasive measurement of blood components by spectrum technology. Dynamic Spectrum theory provides excellent ideas for researchers, but only broadband light source and high-resolution spectrograph were used in correlational studies for a long time. The large number of wavelengths needed for analysis limits the further development of Dynamic Spectrum method. In order to remove redundancy information and make the devices low-cost and integrated, the method of Wavelength selection on the basis of Variable Importance in Projection (VIP) analysis was proposed. Variables with less importance were removed and wavelengths with great explanation power were retained after VIP analysis the number of wavelengths was reduced from 586 to 64. PLS model with 64 wavelengths get a satisfactory predict result that the MREP is 1.82%. The significance test through Bootstrap method validate the selected wavelengths' explanation power. Moreover, the study pointed out the sensitive wavelengths in Dynamic Spectrum method for the first time. Study also took the first step toward the practical application of Dynamic Spectrum and laid the foundation of low-cost on-line analysis, and it also provided valuable references and new ideas for spectral analysis in other areas.

Discovery of 2-Aminothiazole-4-carboxylic Acids as Broad-Spectrum Metallo-ß-lactamase Inhibitors by Mimicking Carbapenem Hydrolysate Binding.

Metallo-ß-lactamases (MBLs) are zinc-dependent enzymes capable of hydrolyzing all bicyclic ß-lactam antibiotics, posing a great threat to public health. However, there are currently no clinically approved MBL inhibitors. Despite variations in their active sites, MBLs share a common catalytic mechanism with carbapenems, forming similar reaction species and hydrolysates. We here report the development of 2-aminothiazole-4-carboxylic acids (AtCs) as broad-spectrum MBL inhibitors by mimicking the anchor pharmacophore features of carbapenem hydrolysate binding. Several AtCs manifested potent activity against B1, B2, and B3 MBLs. Crystallographic analyses revealed a common binding mode of AtCs with B1, B2, and B3 MBLs, resembling binding observed in the MBL-carbapenem product complexes. AtCs restored Meropenem activity against MBL-producing isolates. In the murine sepsis model, AtCs exhibited favorable synergistic efficacy with Meropenem, along with acceptable pharmacokinetics and safety profiles. This work offers promising lead compounds and a structural basis for the development of potential drug candidates to combat MBL-mediated antimicrobial resistance.