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The present study examined the pharmacokinetics of IMM‐H012 in rat plasma, utilizing ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile–0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2 ng/mL, and the linearity of IMM‐H012 in rat plasma was found to be acceptable within the range of 2–2000 ng/mL (R2 > 0.995). The intra‐day and inter‐day precision relative standard deviation was less than 14% of IMM‐H012 in rat plasma. The matrix effect was within the range of 102%–107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM‐H012 in rats after oral administration were successfully studied using UPLC‐MS/MS. [ABSTRACT FROM AUTHOR]

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

A rejuvenating composite seal (RCS) consists of a chip seal and a micro-surfacing (MS). There are two reasons for RCS's poor application effect in China and less frequent application than that of MS: first, the material amount of a composite seal is determined largely based upon experience and lacks a theoretical basis; and second, the composite seal cannot achieve the expected service life. The objective of this study is to determine an appropriate technique to prepare RCS in the laboratory and verify its long-term water stability. Based on an improved sweep test, a method to determine the rate at which to apply the rejuvenating emulsified asphalt used in a chip seal was established. Through the wet track abrasion test and the loaded wheel test, the proper proportion of materials in the MS mix was determined. The material dosage and technique to prepare the RCS was determined by the matrix analysis method based on a multitarget orthogonal test, and its long-term water stability was determined by immersion and freeze-thawing. The results showed that the material dosage of the chip seal was quantitatively determined by an improved sweeping test, the preparation process and material dosage of the composite seal were quantitatively determined by matrix analysis, and the resulting composite seal had reasonable structure and good comprehensive performance. The findings of this paper can provide theoretical guidance for the promotion and application of composite seals in China. [ABSTRACT FROM AUTHOR]

This investigation aims to observe the effects of demodex infection and meibomian gland function in recurrent corneal erosion syndrome (RCES), as well as the efficacy of intense pulsed light (IPL) in treating RCES. The study enrolled thirty patients diagnosed with RCES (30 eyes) alongside a control group of thirty-one individuals (31 eyes). Both cohorts underwent a series of diagnostic evaluations, including eyelash sampling, Demodex mite enumeration, infrared imaging of the meibomian glands, and blepharolipin scoring. The RCES subjects were further categorized into two subgroups upon stabilization for comparative analysis of treatment outcomes: the RCES-A subgroup received IPL therapy (16 patients), and the RCES-B subgroup was administered medication treatment (14 patients). Post-treatment, all participants were re-evaluated using the initial diagnostic procedures to monitor for recurrence. Preliminary findings indicated significant differences between the RCES and control groups in terms of meibomian gland scores (4 [3.0, 4.0] vs. 2 [1.0, 3.0]), blepharolipin scores (15.5 [11.0, 16.8] vs. 8.0 [5.5, 10.0]), and lid margin scores (3.0 [2.8, 3.0] vs. 2.0 [1.0, 3.0]), with P < 0.01 for all comparisons. Additionally, the Demodex count was significantly higher in the RCES group (8.0 [4.0,9.0]) compared to the control (0 [0, 2]) (Z = - 4.13, P = 0.00), with a Demodex positivity rate of 83.3% in the RCES group versus 38.7% in the control group (χ2 = 7.60, P < 0.01). Post-treatment, the RCES-A subgroup exhibited significant improvements in meibomian gland loss scores, blepharolipin scores, lid margin abnormality scores, and a reduction in Demodex counts (P < 0.01), with a post-treatment Demodex positivity rate of 56.3% (P = 0.11). During the follow-up, the RCES-A subgroup experienced a lower relapse rate compared to the RCES-B subgroup (1 vs. 6 patients). The findings suggest a correlation between meibomian gland dysfunction and Demodex infestation with the incidence of RCES. The application of IPL therapy in combination with meibomian gland massage demonstrates significant potential in enhancing meibomian gland functionality, reducing Demodex counts, and effectively mitigating the recurrence of RCES. Clinical trial registration: https://www.chictr.org.cn/ ChiCTR2000039494 (30/10/2020)., (© 2024. The Author(s).)

Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and Snail. In summary, the lncSNHG12/Dio2/Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)