Wide visible-range activatable fluorescence ZnSe:Eu3+/Mn2+@ZnS quantum dots: local atomic structure order and application as a nanoprobe for bioimaging.

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu3+/Mn2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu3+/Mn2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu3+ concentration at a fixed amount of Mn2+, systematically enhancing the Mn2+ emission intensity via energy transfer from the Eu3+ to Mn2+ ion. The ZnSe:Eu3+/Mn2+@ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

Rare case of diabetic neuropathic cachexia along with diabetic amyotrophy.

A 65-year-old patient with background of alcohol excess and previous gunshot wounds was admitted with significant weight loss, leg cramps, dizziness and lethargy for the last 3 months. He was diagnosed with type 2 diabetes mellitus in July 2020 and was started on Metformin and Gliclazide by his in July; he was later commenced on alogliptin and empaglaflozin by diabetes specialist nurse in early August. He also had generalised muscle wasting, dorsal guttering in both hands and was cachectic when he presented to hospital. His haemoglobin A1c (HbA1c) was 124 mmol/mol in July 2020 and was 63 mmol/mol in September 2020. The patient had negative autoimmune and TB screen. CT abdomen/pelvis and CT lumbosacral spine that showed mild diverticular disease and bilateral L5 spondylolysis with L5-S1 spondylotic changes. Electrophysiological studies confirmed sensory motor peripheral neuropathy. Patient was diagnosed with diabetic neuropathic cachexia secondary to poorly controlled diabetes and was commenced on 30 units two times per day of NovoMix 30 insulin; this was adjusted to 24 units two times per day in endocrine clinic 3 months later, after gaining 10 kg in weight. Good glycaemic control is key to the management of such cases and, therefore, we recommend early referral to diabetes specialist input for consideration of insulin therapy.