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.     

Polyetherimide-LaNi5 composite films for hydrogen storage applications

This study investigates the preparation of polyetherimide (PEI) – LaNi₅ composites films for hydrogen storage. Prior to the polymer addition, LaNi₅ was ball-milled at different conditions (250, 350, and 450 RPM) and annealed at 500 °C for 1 h under vacuum. The composites were produced with BM-LaNi₅-350 (PEI/LaNi₅-350) and annealed BM-LaNi₅-350 (PEI/LaNi₅-350-TT). Membranes were successfully produced through solvent casting assisted by an ultrasonic bath. The particles dispersion and the film morphology did not change after hydrogenation cycles. In the H₂ sorption experiments at 43 °C and 20 bar, the films stored H₂ without incubation time; both samples reached a capacity of ~0.6 wt%. The H₂ sorption kinetics of PEI/LaNi₅-350 was comparable to that of BM-LaNi₅-350, whereas PEI/LaNi₅-350-TT presented significantly slower kinetics. LaNi₅ oxidation was hindered by PEI, showing that it can be explored to improve metal hydrides air resistance. The results demonstrated that PEI films filled with LaNi₅ are promising materials for hydrogen storage.     

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson’s Disease Model

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson’s disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP⁺)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP⁺-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.     

Dynamic Oscillation via Negative Differential Resistance in Type III Junction Organic/Two-Dimensional and Oxide/Two-Dimensional Transition Metal Dichalcogenide Diodes

Among many of 2D semiconductor-based devices, type III PN junction diodes are given special attentions due to their unique function, negative differential resistance (NDR). However, it has been found uneasy to achieve well-matched type III PN junctions from 2D–2D van der Waals heterojunctions. Here, the authors present other alternatives of type III heterojunctions, using 2D p-MoTe₂/organic n-type dipyrazino[2,3-f:2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile (HAT-CN) and 2D p-WSe₂/n-MoO_x systems. Those junction diodes appear to well-demonstrate static and dynamic NDR behavior via resonant tunneling and electron–hole recombination. Extended to an inverter circuit, p-MoTe₂/n-HAT-CN diode enables multilevel inverter characteristics as monolithically integrated with p-MoTe₂ channel field effect transistor. The same NDR diode shows dynamic LC oscillation behavior under a constant DC voltage, connected to an external inductor. From p-WSe₂/n-MoO_x oxide diode, similar NDR behavior to those of p-MoTe₂/n-HAT-CN is again observed along with LC oscillations. The authors attribute these visible oscillation results to high peak-to-valley current ratios of their organic or oxide/2D heterojunction diodes.     

Antimicrobial and Anticancer Properties of Synthetic Peptides Derived from the Wasp Parachartergus fraternus

Agelaia-MPI and protonectin are antimicrobial peptides isolated from the wasp Parachartergus fraternus that show antimicrobial and neuroactive activities. Previously, two analogues of these peptides, neuroVAL and protonectin-F, were designed to reduce nonspecific toxicity and improve potency. Here, the three-dimensional structures of neuroVAL, protonectin and protonectin-F were determined by using circular dichroism and NMR spectroscopy. Antibacterial, antifungal, cytotoxic and hemolytic activities were tested for the parent peptides and analogues. All peptides showed moderate antimicrobial activity against Gram-positive bacteria, with agelaia-MPI being the most active. Protonectin and protonectin-F were found to be toxic to cancerous and noncancerous cell lines. Internalization experiments revealed that these peptides accumulate inside both cell types. By contrast, neuroVAL was nontoxic to all tested cells and was able to enter cells without accumulating. In summary, neuroVAL has potential as a nontoxic cell-penetrating peptide, while protonectin-F needs further modification to realize its potential as an antitumor peptide.     

Sulfonylguanidine Derivatives as Potential Antimelanoma Agents

Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

方腔内耦合传热传质非对称流动数值模拟

对带有质热源的方腔内流体传热传质进行数值研究。针对不同Ra、Nc、Sr和Df，探究对称方腔内流体传热传质的分岔特性。结果表明：存在临界Ra_c使流体流动形态发生转变，当Ra<Ra_c时，流体流线、温度场和浓度场对称分布；当Ra>Ra_c时，流体发生偏斜。增大浮升力，流体更易发生分岔现象。增强Soret和Dufour效应可增强传热对称性并增大流体发生分岔的临界Rayleigh数。     

汽车悬架球头拉杆冷成形技术

为提高生产效率、改变原来通过车削加工汽车悬架球头拉杆的方式,提出了一种球头拉杆的多工位冷镦成形工艺。基于DEFORM-3D软件建立了有限元模型,对球头拉杆的塑性成形过程进行了仿真,研究了预成形凸模入模角α、预成形凹模圆角R1、终成形凹模圆角R2以及终成形凹模入模角β等工艺参数对球头拉杆成形的影响,并进行了正交试验,以模具在球头拉杆成形过程中所受载荷及工件损伤值为优化目标,获得了合理的工艺参数组合。结果表明:在保证工件成形质量及模具寿命的前提下,当预成形凸模入模角α为30°、预成形凹模圆角R1为12 mm、终成形凹模圆角R2为3 mm、终成形凹模入模角β为60°时,模具载荷及工件损伤有显著的降低。采用优化后的参数进行试模生产,工件成形质量较好,验证了模拟结果的可信性,能够有效地指导工艺设计人员的设计工作。