Identification of related long non-coding RNAs and mRNAs in subclinical hypothyroidism complicated with type 2 diabetes by transcriptome analysis — a preliminary study

Introduction: The pathology mechanism of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes remained uncertain. We aimed to find potential related long non-coding RNAs (lncRNAs) and mRNAs in the above diseases. Material and methods: Transcriptome sequencing was performed in three patients with subclinical hypothyroidism (S), three patients with subclinical hypothyroidism complicated with type 2 diabetes (SD), and three healthy controls (N). Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were screened in S vs. N, SD vs. N, and SD vs. S group, and the nearby and co-expressed DEmRNAs of DElncRNAs were screened in S vs. N and SD vs. N. Moreover, functional analysis of DEmRNAs was then performed by Metascape. Results: In total, 465, 1058, and 943 DEmRNAs were obtained in S vs. N, SD vs. N, SD vs. S, respectively, and 191 overlapping genes were obtained in S vs. N and SD vs. N group. Among which, LAIR2, PNMA6A, and SFRP2 were deduced to be involved in subclinical hypothyroidism, and GPR162, APOL4, and ANK1 were deduced to be associated with subclinical hypothyroidism complicated with type 2 diabetes. A total of 50, 100, and 88 DElncRNAs were obtained in S vs. N, SD vs. N and SD vs. S, respectively. Combining with the interaction network of DElncRNA-DEmRNA, PAX8-AS1, co-expressed with KIR3DL1, was identified to function in subclinical hypothyroidism, and JHDM1D-AS1, co-expressed with ANK1, was deduced to play a role in subclinical hypothyroidism complicated with type 2 diabetes. Conclusions: Dysfunctional lncRNAs and mRNAs may be involved in the development of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes.

Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect and in vivo pharmacokinetic study

Curcumin (CUR) is a natural polyphenol extract with significant antioxidant and anti-inflammatory effects, which indicates its great potential for neuroprotection. Lactoferrin (LF), a commonly used oral carrier and targeting ligand, has not been reported as a multifunctional nanocarrier for nose-to-brain delivery. This study aims to develop a nose-to-brain delivery system of curcumin-lactoferrin nanoparticles (CUR-LF NPs) and to further evaluate the neuroprotective effects in vitro and brain accumulation in vivo. Herein, CUR-LF NPs were prepared by the desolvation method with a particle size of 84.8 ± 6.5 nm and a zeta potential of +22.8 ± 4.3 mV. The permeability coefficient of CUR-LF NPs (4.36 ± 0.79 × 10−6 cm/s) was 50 times higher than that of CUR suspension (0.09 ± 0.04 × 10−6 cm/s) on MDCK monolayer, indicating that the nanoparticles could improve the absorption efficiency of CUR in the nasal cavity. Moreover, CUR-LF NPs showed excellent protection against Aβ25-35-induced nerve damage in PC12 cells. In vivo pharmacokinetic studies showed that the brain-targeting efficiency of CUR-LF NPs via IN administration was 248.1%, and the nose-to-brain direct transport percentage was 59.7%. Collectively, nose-to-brain delivery of CUR-LF NPs is capable of achieving superior brain enrichment and potential neuroprotective effects

Subtle features of delamination in cross-ply laminates due to low speed impact

In cross-ply laminates, the shape of delamination areas, which form due to low velocity impact, have two subtle features, which have been observed consistently in numerous experiments. Those are the pointed delamination tips and the intact zone between the lobes of delamination. However, there have not been any account available in the literature how they can be consistently captured through numerical modelling, and hence these features in published modelling results were often absent. It is the objective of this paper to identify the underlying modelling considerations so that these features can be captured with confidence. A key and unique reason has been identified in each case. Namely, inclusion of intra-laminar damage allows to reproduce the pointed delamination tips, while the gap between the lobes of delamination can be captured by models with sufficiently refined mesh, where friction between the laminas is taken into account. The capability of capturing these subtle features helps to raise the level of fidelity on the simulation of delamination due to impact

Hyperconjugated side chained benzodithiophene and 4,7-di-2-thienyl-2,1,3-benzothiadiazole based polymer for solar cells

A novel donor-acceptor (D-A) copolymer (P3TBDTDTBT), including hyperconjugated side chained benzodithiophene as a donor and 4,7-di-2-thienyl-2,1,3-benzothiadiazole (DTBT) as an acceptor, was designed and synthesized. Due to the introduction of the hyperconjugated side chain, the resultant polymer exhibited good thermal stability with a high decomposition temperature of 437 degrees C, a low band-gap of 1.67 eV with an absorption onset of 742 nm in the solid film, and a deep highest occupied molecular orbital (HOMO) energy level of -5.26 eV. Finally, the polymer solar cell (PSC) device based on this polymer and [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM) showed the best power conversion efficiency (PCE) of 3.57% with an open-circuit voltage (V-oc) of 0.78 V, a short-circuit current density (J(sc)) of 8.83 mA cm(-2) and a fill factor (FF) of 53%

Practical, regulatory and clinical considerations for development of inhalation drug products

The formulation and device collectively constitute an inhalation drug product. Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction. From the points of formulation, device and patient use, this article summarizes the inhalation drugs, including pressurized metered dose inhaler (pMDI), dry powder inhaler (DPI), and nebulizer that are currently available in the US and UK markets. It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency)