Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Modeling of the Magnetization and Magnetocaloric Effect in Ni2MnGa Heusler Alloy with the Effective Field Theory

Journal of Low Temperature Physics - This study modeled and investigated the magnetocaloric effect in Ni2MnGa Heusler alloy characterized by its magnetic entropy change (ΔSm) and its...     

Fat Distribution and Lipid Profile of Young Adults with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Enzyme Deficiency

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case–control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18–31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m², p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m², p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m², p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m², p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m², p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m², p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = −0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.     

和成矿业洗矿系统改造实践

针对和成矿业井下原矿含泥量和含水量较大，且矿泥中存在绿泥石、高岭土等黏土类矿物，造成供矿系统粘堵严重，系统台时量仅为设计水平一半的问题，对原矿进行了洗矿工艺研究。通过洗矿工艺，将原矿中的矿块和矿泥分离，实现矿块和矿泥按粒度分选，彻底解决了供矿系统粘堵严重的问题，稳定了磨选系统给矿量。     

南非铜尾矿回收铁选矿试验

为了综合回收现有南非铜尾矿中的有价铁元素，在试验室对该铜尾矿进行了回收铁的可选性试验研究。研究结果表明：该铜尾矿铁品位为59.36%，磁性铁含量为57.99%，当原矿磨矿细度为-0.074 mm 58%时，经两次磁选后，可获得产率为88.95%，铁品位为65.69%，铁回收率为98.43%的铁精矿。