Glycosidase-targeting small molecules for biological and therapeutic applications.

Glycosidases are ubiquitous enzymes that catalyze the hydrolysis of glycosidic linkages in oligosaccharides and glycoconjugates. These enzymes play a vital role in a wide variety of biological events, such as digestion of nutritional carbohydrates, lysosomal catabolism of glycoconjugates, and posttranslational modifications of glycoproteins. Abnormal glycosidase activities are associated with a variety of diseases, particularly cancer and lysosomal storage disorders. Owing to the physiological and pathological significance of glycosidases, the development of small molecules that target these enzymes is an active area in glycoscience and medicinal chemistry. Research efforts carried out thus far have led to the discovery of numerous glycosidase-targeting small molecules that have been utilized to elucidate biological processes as well as to develop effective chemotherapeutic agents. In this review, we describe the results of research studies reported since 2018, giving particular emphasis to the use of fluorescent probes for detection and imaging of glycosidases, activity-based probes for covalent labelling of these enzymes, glycosidase inhibitors, and glycosidase-activatable prodrugs.

All-Gas-Phase Synthesis of Heterolayered Two-Dimensional Nanohybrids Decorated with Metallic Nanocatalysts for Water Splitting.

Herein, a sequential gas-phase process involving air jet milling followed by chemical vapor deposition (CVD), is demonstrated to be an efficient strategy for the fabrication of heterolayered 2D nanohybrids (2DNHs) decorated with nanocatalysts. Tens of grams of the nanohybrids, which is a substantial quantity at the laboratory scale, are produced in the absence of solvents and water, and without the need for an extra purification procedure. Air jet milling enables the development of binary/ternary heterolayered structures consisting of graphene, WSe2 , and/or MoS2 via the gas-phase co-exfoliation of their bulk counterparts. Based on the X-ray photoelectron and Raman spectroscopy data, the heterolayers of the 2DNHs exert chemical and electronic effects on each other, while diminishing the interactions between same-component layers. Moreover, the electrochemically active surface area increases by >190% and the charge transfer resistance decreases by >35%. CVD is performed to introduce Pt and Ru nanoparticles with diameters of a few nanometers as additional electrocatalysts into the 2DNHs. The nanocatalyst-decorated 2DNHs show excellent performance for the production of hydrogen and oxygen gases in water-splitting cells. Notably, the proposed all-gas-phase processes allow for the large-scale production of functional 2DNHs with minimal negative environmental impact, which is crucial for the commercialization of nanomaterials.

Surfactant-in-Polymer Templating for Fabrication of Carbon Nanofibers with Controlled Interior Substructures: Designing Versatile Materials for Energy Applications.

A simple, scalable, surfactant-in-polymer templating approach is demonstrated to create controlled long-range secondary substructures in a primary structure. A metal bis(2-ethylhexyl) sulfosuccinate (MAOT) as the surfactant is shown to be capable of serving as a sacrificial template and metal precursor in carbon nanofibers. The low interfacial tension and controllable dimensions of the MAOT are maintained in the solid-phase polymer, even during electrospinning and heat-treatment processes, allowing for the long-range uniform formation of substructures in the nanofibers. The MAOT content is found to be a critical parameter for tailoring the diameter of the nanofibers and their textural properties, such as size and volume of interior pores. The metal counterion species in the MAOT determine the introduction of metallic phases in the nanofiber interior. The incorporation of MAOT with Na as the counterion into the polymer phase leads to the formation of a built-in pore structure in the nanofibers. In contrast, MAOT with Fe as a counterion generates unique iron-in-pore substructures in the nanofibers (FeCNFs). The FeCNFs exhibit outstanding charge storage and water splitting performances. As a result, the MAOT-in-polymer templating approach can be extended to combinations of various metal precursors and thus create desirable functionalities for different target applications.

Morphology-Dependent Ambient-Condition Growth of Perovskite Nanocrystals for Enhanced Stability in Photoconversion Device.

CsPbBr3 perovskite nanocrystals with two different dimensionalities were synthesized at different temperatures and then integrated as optoelectronic transducers into transistor-type photoconversion devices. Postsynthesis transformation was observed for two-dimensional (2D) nanoplatelets, while the transformation was rarely found in 3D nanocubes. At ambient temperature and pressure, neighboring nanoplatelets made facet-to-facet contact and then fused into larger 2D nanoplatelets (2-5 times) without defects. The coalescence of 2D nanoplatelets at the ambient condition lowered the density of defects at the surface of the nanocrystals and thus could facilitate effective and stable photoconversion behavior in the nanocrystal film integrated into the device. Consequently, the ambient-condition aging of 2D nanoplatelets on device substrate led to 3 times higher retention in photoconversion performance. Importantly, these results provide a new concept of how perovskite nanocrystals can be integrated into a device for enhanced stability in device performance.

Prevalence of Women with Dense Breasts in Korea: Results from a Nationwide Cross-sectional Study.

PURPOSE: Women with dense breast are known to be at high risk for breast cancer, but their prevalence and number of Korean women are unknown. The current study was to investigate the distribution of mammographic breast density by age of women undergoing screening mammography, and to estimate the prevalence of Korean women with dense breasts, quantitatively. MATERIALS AND METHODS: For obtaining a nationwide representative sample, 6,481 mammograms were collected from 86 screening units participated in the National Cancer Screening Program for breast cancer. Based on the American College of Radiology Breast Imaging Reporting and Data System classification, breast density was evaluated by six breast radiologists, qualitatively. We applied these breast density distributions to age-specific counts of the Korean women population derived to mid-year 2017 to estimate the number of Korean women with dense breasts. RESULTS: Overall, 54.4% (95% confidence interval [CI], 52.9% to 55.8%) of women 40 to 69 years of age had heterogeneously or extremely dense breasts, and this proportion was inversely associated with age. Based on the age distribution of Korean women, we estimated that 6,083,000 women (95% CI, 5,919,600 to 6,245,600) age 40-69 years in Korean have dense breasts. Women aged 40-49 years (n=3,450,000) accounted for 56.7% of this group. CONCLUSION: More than half of Korean women aged 40 and over have dense breasts. To prevent breast cancer effectively and efficiently, it is necessary to develop a new personalized prevention strategy considering her status of breast density.

Analysis of Participant Factors That Affect the Diagnostic Performance of Screening Mammography: A Report of the Alliance for Breast Cancer Screening in Korea.

OBJECTIVE: To analyze participant factors that affect the diagnostic performance of screening mammography. MATERIALS AND METHODS: We enrolled 128756 cases from 10 hospitals between 2005 and 2010. We analyzed recall rate, cancer detection rate (CDR) per 1000 examinations, positive predictive value (PPV), sensitivity, specificity, false positive rate (FPR), and interval cancer rate (ICR) per 1000 negative examinations according to participant factors including age, breast density, and number of visit to the same institution, and adjusted for confounding variables. RESULTS: Increasing age improved recall rates (27.4% in 40's, 17.5% in 50's, 11.1% in 60's, and 8.6% in 70's), CDR (2.7, 3.2, 2.0, and 2.4), PPV (1.0, 1.8, 1.8, and 2.8%), sensitivity (81.3, 88.8, 90.3, and 94.7%), specificity (72.7, 82.7, 89.0, and 91.7%), and FPR (27.3, 17.3, 11.0, and 8.4%) (p < 0.05). Higher breast density impaired recall rates (4.0% in P1, 9.0% in P2, 28.9% in P3, and 27.8% in P4), PPV (3.3, 2.3, 1.2, and 1.3%), specificity (96.1, 91.2, 71.4, and 72.5%), and FPR (3.9, 8.9, 28.6, and 27.6%) (p < 0.001). It also increased CDR (1.3, 2.1, 3.3, and 3.6) and ICR (0.2, 0.3, 0.6, and 1.6) (p < 0.05). Successive visits to the same institution improved recall rates (20.9% for one visit, 10.7% for two visits, 7.7% for more than three visits), PPV (1.6, 2.8, and 2.7%), specificity (79.4, 89.6, and 92.5%), and FPR (20.6, 10.4, and 7.5%) (p < 0.001). CONCLUSION: Young age and dense breasts negatively affected diagnostic performance in mammography screening, whereas successive visits to the same institution had a positive effect. Examinee education for successive visits to the same institution would improve the diagnostic performance.