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Abstract A significant number of steep cracks are frequently encountered in underground engineering, posing a threat to operation. The high-pressure grouting method is a commonly utilized repair technique. Nevertheless, conventional grout is prone to displacement due to its weight, making it challenging to ensure adequate filling of the cracks. Therefore, this study aims to develop a grouting material with targeted displacement and anchoring properties. Firstly, an optimal magnetic slurry composition was determined through an orthogonal test. Subsequently, XRD and SEM were used to analyze the impact of the magnetic field on the composition distribution, internal pore structure, and transient viscosity of the slurry. Afterwards, a model for localized grout diffusion under magnetic was established. The results show that the application of a magnetic field caused the slurry to compact due to magnetic forces, reducing its porosity. Moreover, the dynamic viscosity of the slurry increased exponentially with rising magnetic induction intensity. Notably, a 40.5% increase in the diffusion area was observed when the magnetic field intensity rose from 2500 to 4500 GS. The error between the measured and theoretical values of the magnetic slurry diffusion model was only 8.91%, indicating the model's accuracy in describing the slurry diffusion process under magnetic field influence.

Abstract Laryngeal squamous cell carcinoma (LSCC) is a common malignancy of the head and neck. Recently, circular RNA (circRNA) has been studied extensively in multisystem diseases. However, there are few research on biological functions and molecular mechanisms of circRNAs in LSCC. CircRNA array was used to detect the differentially expressed circRNAs. Kaplan–Meier and cox regression analysis were used to identify survival based on circMMP9. The qRT-PCR, RNase R treatment, sanger sequencing and in situ hybridization were used to verify circMMP9 expression, characteristics and localization in LSCC tissues and cells. Functionally, colony formation, MTS, transwell and in vivo assays were proceeded to detect the biological function of circMMP9 in LSCC progression. The RNA-seq was conducted to identify the molecular targets of circMMP9. Mechanically, MeRIP, RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried on to verify the regulatory mechanism of circMMP9. CircMMP9 was discovered upregulated in LSCC tissues and cells, and high level of circMMP9 was associated with poor prognosis, low degree of pathological grading, high TNM stage and lymph node metastasis of LSCC. CircMMP9 knockdown prevented LSCC progression both in vitro and in vivo, whereas, circMMP9 overexpression had the opposite effect. CircMMP9 was stabilized by IGF2BP2 in m6A-dependent manner. TRIM59 was identified as downstream target of circMMP9. CircMMP9 recruited ETS1 to stimulate TRIM59 transcription. Moreover, TRIM59 accelerated LSCC progression via activating the PI3K/AKT signal pathway. Our findings offered a unique regulatory mechanism for circMMP9 in LSCC, as well as a novel proof that circMMP9 may be utilize as a diagnostic marker and therapeutic target for LSCC patients.

Abstract Traumatic or degenerative joint pain is abundant in the population. Symptom relief by intra- and periarticular glucocorticoid administration is frequently used, however may have potentially devastating effects, changing the normal healing process of the joint. Mesenchymal stem cells (MSCs) are important for wound-healing processes due to their multipotency in regenerating osteoblasts, chondrocytes and adipocytes but also have immunomodulatory properties. The aim of this study was to investigate the impact of triamcinolone acetonide (TA) a common glucocorticoid administrated intra- and periarticularly, on human bone marrow derived MSC viability, functionality, multi-lineage differentiation and transcriptomic output. We found that TA treatment induced apoptosis and promoted adipogenesis while impairing chondrogenesis of MSCs. RNA sequencing indicated that TA modulated the inflammatory response of MSCs, which may have an impact on the immunologic environment where the inflammatory phase is a physiological part of the natural healing process. These data indicate that triamcinolone acetonide should be used with consideration bearing the patient’s outcome in mind, with the intention to optimize joint recovery and homeostasis.

Abstract The PI3K/Akt signalling pathway is associated with the occurrence and development of tumours and significantly affects the prognosis of patients. We established a predictive signature based on the PI3K/Akt pathway to predict the prognosis of patients. The RNA-seq and clinical data of laryngeal cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Three lncRNAs (MNX1-AS1, LINC00330, LSAMP-AS1) were selected through univariate, multivariate Cox and log-rank test analysis to establish a prognostic signature. The patients were then divided into high-risk and low-risk groups based on their risk score. In the TCGA training set, the survival time of the high-risk group was shorter than that of the low-risk group (P

Red blood cells (RBCs) are phagocytosed in the spleen in sickle cell disease and malaria. Here, Cao et al. show that high mannose N-glycans, exposed on diseased or oxidized RBC surfaces, bind mannose receptor CD206 on host cells, mediating phagocytosis.

Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether any other co-factors associate with TAPBPR, which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on MHC class I molecules, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex.

Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents' target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical.

With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice.

With the development of increasingly large and complex genomic and proteomic data sets, an enhancement in the complexity of available Venn diagram analytical programs is becoming increasingly important. Current freely available Venn diagram programs often fail to represent extra complexity among datasets, such as regulation pattern differences between different groups. Here we describe the development of VennPlex, a program that illustrates the often diverse numerical interactions among multiple, high-complexity datasets, using up to four data sets. VennPlex includes versatile output features, where grouped data points in specific regions can be easily exported into a spreadsheet. This program is able to facilitate the analysis of two to four gene sets and their corresponding expression values in a user-friendly manner. To demonstrate its unique experimental utility we applied VennPlex to a complex paradigm, i.e. a comparison of the effect of multiple oxygen tension environments (1-20% ambient oxygen) upon gene transcription of primary rat astrocytes. VennPlex accurately dissects complex data sets reliably into easily identifiable groups for straightforward analysis and data output. This program, which is an improvement over currently available Venn diagram programs, is able to rapidly extract important datasets that represent the variety of expression patterns available within the data sets, showing potential applications in fields like genomics, proteomics, and bioinformatics.

Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and GOAT knockout (GOAT(-/-)) mice. Ghrelin(-/-) mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/-) mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/-) and GOAT(-/-) mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/-) mice, yet potentiated in GOAT(-/-) mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/-) mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/-) and GOAT(-/-) mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.