Osteoclast-derived exosomes influence osteoblast differentiation in osteoporosis progression via the lncRNA AW011738/ miR-24-2-5p/ TREM1 axis.

AIMS: To investigate the molecular mechanism of osteoclast-derived exosomes in osteoporosis. MAIN METHODS: RANKL induced osteoclast model was screened for significantly differentially expressed lncRNAs and mRNAs by whole RNA sequencing. Exosomes were characterized using electron microscopy, western blotting and nanosight. Overexpression or knockdown of AW011738 was performed to explore its function. The degree of osteoporosis in an osteoporosis model was assessed by mirco-CT. The osteoclast model, osteoblast differentiation ability and the molecular mechanism of lncRNA AW011738/miR-24-2-5p/TREM1 axis in osteoporosis were assessed by dual luciferase reporter gene assay, Western blotting (WB), immunofluorescence and ALP staining. Bioinformatics was used to predict interactions of key osteoporosis-related genes with miRNAs, transcription factors, and potential drugs after upregulation of AW011738. To predict the protein-protein interaction (PPI) network associated with key genes, GO and KEGG analyses were performed on the key genes. The ssGSVA was used to predict changes in the immune microenvironment. KEY FINDINGS: Osteoclast-derived exosomes containing lncRNA AW011738 decreased the osteogenesis-related markers and accelerated bone loss in OVX mice. Osteoclast (si-AW011738)-derived exosomes showed a significant increase in biomarkers of osteoblast differentiation in vitro compared to the si-NC group. As analyzed by mirco-CT, tail vein injected si-AW011738 OVX mice were less osteoporotic than the control group. AW011738 inhibited osteoblast differentiation by regulating TREM1 expression through microRNA. Meanwhile, overexpression of miR-24-2-5p inhibited TREM1 expression to promote osteoblast differentiation. SIGNIFICANCE: Osteoclast-derived exosomes containing lncRNA AW011738 inhibit osteogenesis in MC3T3-E1 cells through the lncRNA AW011738/miR-24-2-5p/TREM1 axis and exacerbate osteoporosis in OVX mice.

Co contamination of Si: Plating & aging.

Cobalt has emerged as a vital material in 10 nm technology for localized interconnect layers, potentially offering a compelling alternative to Cu-based interconnects. In this study, we subjected the contamination arising from the presence of cobalt atoms in silicon to comprehensive investigation, employing electron transmission electron microscopy (TEM) observations in conjunction with first-principles calculations. The results show that a dense CoSi layer with a thickness of a few nanometers is formed at the interface of cobalt and Si. The CoSi layer blocks the diffusion of Co atoms into Si. This is due to the semiconducting nature of the covalent bond formed between Co and Si, leading to the emergence of a forbidden zone at the Co/CoSi interface. The diffusion of Co into CoSi is governed by the atomic exchange mechanism, however, the local distortion of the periodic atomic potential due to the presence of the forbidden zone at the Co/CoSi interface hinders the diffusion of Co into Si. Therefore, the deposition of a Co metal layer on a Si chip does not require an additional barrier layer.

Structure Elucidation of a Novel Polysaccharide Isolated from Euonymus fortunei and Establishing Its Antioxidant and Anticancer Properties.

Euonymusfortunei polysaccharides (EFPs) have not been extensively investigated yet in terms of their extraction and biological activity. The orthogonal experimental design was employed in this study to evaluate the optimum yield of EFPs. A maximum yield of 2.63 ± 0.23% was attained using material-liquid ratios of 60 mL/g, extraction temperature of 80°C, ultrasonic power of 144 W, and extraction time of 75 mins. The polysaccharide content reached 53.47 ± 0.31% when deproteinized thrice. An analysis of monosaccharide composition revealed that these polysaccharides consist of Gal, Glc, Man, Fuc, and Rha with a molar ratio of 7.14 ∶ 23.99 ∶ 6.29 ∶ 6.55 ∶ 1.00, respectively, in EFPs. Subsequently, the in vitro scavenging capacities of 2,2-diphenylpicrylhydrazyl (DPPH) and ·OH and superoxide anion radicals, along with the reducing power of EFPs, were studied. Results revealed that EFPs have higher antioxidant activity, particularly ·OH scavenging, as well as reducing power, as compared to Astragalus polysaccharides (ASPs) and Lycium barbarum polysaccharides (LBPs). The Cell Counting Kit-8 (CCK-8) method was used to evaluate the effects of different concentrations of polysaccharides on SKOV3 cell proliferation, and the results revealed their inhibition at concentrations in the range of 200-800 µg/mL. In addition, findings from flow cytometry further confirmed that EFPs blocked the cell cycle at G0/G1 and S phases and induced SKOV3 cell apoptosis. In a word, EFPs could be exploited and used further based on the experimental results from this study.

Empowering caregivers of children with bronchiolitis obliterans: The effectiveness of an internet-based follow-up platform.

OBJECTIVE: Limited evidence on home care and need for long-term individualized follow-up highlight the importance of developing an Internet-based follow-up platform to support caregivers of children with Bronchiolitis Obliterans (BO). This Study aims to explore and test the potential benefits of this platform by comparing family management, medication compliance and clinical systems. STUDY DESIGN AND METHODS: A two-arm, single-blind randomized controlled trial was conducted on 168 children with BO and their families from January 2022 to October 2022. Families were randomly divided into Internet-based follow-up group and conventional follow-up group with a ratio of 1:1. Scores of family management measures (FaMM), 8-item of Morisky Medication Adherence (8-MMAS) and BO clinical symptoms of both groups were collected at three points of time: the day of discharge (T1), 3 months after discharge (T2), and 6 months after discharge (T3). The changes of each group due to intervention were compared by repeated-measures ANOVA. RESULTS: 90 families completed the trial, including 48 in the Internet-based follow-up group and 42 in the conventional follow-up group. The results showed a significant difference in the group-by-time interaction on the scores of Child's Daily Life, Condition Management Ability and Parental Mutuality (p < 0.05). No group-by-time effect was found on the scores of View of Condition Impact and Family Life Difficulty. Scores of BO clinical symptoms and MMAS-8 showed intra-group, inter-group, and group-by-time effects. CONCLUSIONS: The Internet-based follow-up platform can empower caregivers in enhancing effective family management, improving medication compliance in children with BO, and relieving patients' clinical symptoms. TRIAL REGISTRATION: Chinese Clinical Trials Registry of ChiCTR2200065121 (04/28/2022).

Ruxolitinib improves the inflammatory microenvironment, restores glutamate homeostasis, and promotes functional recovery after spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

A Study of Electroplated Nanoporous Copper Using Aberration-Corrected Transmission Electron Microscopy.

Nanoporous Cu foam is widely applied in many fields such as the packaging of electronic power devices. In this study, a sandwich-structured Cu-Zn eutectic alloy precursor composed of Cu0.53Zn0.47/Cu5Zn8/Cu0.53Zn0.47 is prepared through electroplating. The surface layer of the precursor, Cu0.53Zn0.47, has a flat surface with numerous grain boundaries, which effectively promotes its dealloying behavior. By contrast, Cu5Zn8 has a porous structure, which promotes the dealloying behavior at the center of the precursor. The dealloying of Cu0.53Zn0.47 is dominated by the coherent surface diffusion of Cu atoms, and the crystal lattice and orientation show no changes before and after dealloying. By contrast, the dealloying behavior of Cu5Zn8 requires the renucleation of Cu crystals; in this process, Cu atoms are transported to the surface of the layer by capillary forces to form clusters, which nucleate and grow.

Quercetin inhibits caspase-1-dependent macrophage pyroptosis in experimental folic acid nephropathy.

BACKGROUND: The role of pyroptosis in kidney disease is limited and incomplete. Quercetin, a flavonoid compound present in a variety of fruits, vegetables, and plants, has shown antioxidant and anti-inflammatory properties. This study was designed to validate the importance of pyroptosis in an experimental model of folic acid nephropathy and to explore the effect of quercetin in protecting against pyroptosis. METHODS: Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were used to establish the correlation between pyroptosis and folic acid nephropathy. Immune cell infiltration, network pharmacology and single-cell RNA sequencing analysis were utilized to ascertain the specific target of quercetin in relation to pyroptosis. Finally, quercetin's role was verified in vivo and in vitro. RESULTS: The GSEA analysis revealed a significant correlation between pyroptosis and folic acid nephropathy (NES = 1.764, P = 0.004). The hub genes identified through WGCNA were closely associated with inflammation. Molecular docking demonstrated a strong binding affinity between quercetin and caspase-1, a protein known to be involved in macrophage function, as confirmed by immune cell infiltration and single-cell analysis. Quercetin demonstrated a significant amelioration of kidney injury and reduction in macrophage infiltration in the animal model. Furthermore, quercetin exhibited a significant inhibition of caspase-1 expression, subsequently leading to the inhibition of pro-inflammatory cytokines expression, such as IL-1ß, IL-18, TNF-α, and IL-6. The inhibitory effect of quercetin on macrophage pyroptosis was also confirmed in RAW264.7 cells. CONCLUSION: This study contributes substantial evidence to support the significant role of pyroptosis in the development of folic acid nephropathy, and highlights the ability of quercetin to downregulate caspase-1 in macrophages as a protective mechanism against pyroptosis.

Characterization and treatment of oily sludge: A systematic review.

Oily sludge is a prevalent hazardous waste generated in the petroleum industry, and effectively treating it remains a key challenge for the petroleum and petrochemical sectors. This paper provides an introduction to the origin, properties, and hazards of oil sludge while summarizing various treatment methods focused on reduction, recycling, and harmlessness. These methods include combustion, stabilization/solidification, oxidation and biodegradation techniques, solvent extraction, centrifugation, surfactant-enhanced oil recovery processes as well as freezing-thawing procedures. Additionally discussed are pyrolysis, microwave radiation applications along with electrokinetic method utilization for oily sludge treatment. Furthermore explored are ultrasonic radiation techniques and froth flotation approaches. These technologies have been thoroughly examined through discussions that analyze their process principles while considering influencing factors as well as advantages and disadvantages associated with each method. Based on the characteristics of oily sludge properties and treatment requirements, a selection methodology for choosing appropriate oily sludge treatment technology is proposed in this study. The development direction of processing technology has also been explored to provide guidance aimed at improving efficiency by optimizing existing processing technologies. The paper presents a comprehensive treatment method for oily sludge, ensuring that all the parameters meet the standard requirements.

Active Breathing Coordinator reduces radiation dose to the stomach in patients with left breast cancer.

BACKGROUND/PURPOSE: Gastric dose parameters comparison for deep inspiration breath-hold (DIBH) or free breathing (FB) mode during radiotherapy (RT) for left-sided breast cancer patients (LSBCPs) has not been investigated before. This study aimed to analyze the impact of Active Breath Coordinator (ABC)-DIBH technique on the dose received by the stomach during RT for LSBCPs and to provide organ-specific dosimetric parameters. MATERIALS AND METHODS: The study included 73 LSBCPs. The dosimetric parameters of the stomach were compared between FB and DIBH mode. The correlation between the stomach volume and dosimetric parameters was analyzed. RESULTS: Compared to FB mode, statistically significant reductions were observed in gastric dose parameters in ABC-DIBH mode, including Dmax (46.60 vs 17.25, p < 0.001), D1cc (38.42 vs 9.60, p < 0.001), Dmean (4.10 vs 0.80, p < 0.001), V40Gy (0.50 vs 0.00, p < 0.001), V30Gy (6.30 vs 0.00, p < 0.001), V20Gy (20.80 vs 0.00, p < 0.001), V10Gy (51.10 vs 0.77, p < 0.001), and V5Gy (93.20 vs 9.60, p < 0.001). ABC-DIBH increased the distance between the stomach and the breast PTV when compared to FB, from 1.3 cm to 2.8 cm (p < 0.001). Physiologic decrease in stomach volume was not found from FB to ABC-DIBH (415.54 cm3 vs 411.61 cm3, p = 0.260). The stomach volume showed a positive correlation with V40Gy (r2 = 0.289; p < 0.05), V30Gy (r2 = 0.287; p < 0.05), V20Gy (r2 = 0.343; p < 0.05), V10Gy (r2 = 0.039; p < 0.001), V5Gy (r2 = 0.439; p < 0.001), Dmax (r2 = 0.269; p < 0.05) and D1cc (r2 = 0.278; p < 0.05) in FB mode. While in ABC-DIBH mode, most stomach dosimetric parameters were not correlated with gastric volume. CONCLUSIONS: The implementation of ABC-DIBH in LSBCPs radiotherapy resulted in lower irradiation of the stomach. Larger stomach volume was associated with statistically significantly higher dose irradiation in FB mode. To reduce radiotherapy related side effects in FB mode, patients should be fast for at least 2 hours before the CT simulation and treatment.

Effect of CoSn3 nanocrystals on Sn3Ag plating for electronic packaging.

Plating Sn3Ag on copper substrates represents a crucial electronic packaging technique. In this study, we propose a novel composite plating approach, wherein CoSn3 nanocrystals are deposited within the Sn3Ag coating. The resulting reflowed Sn3Ag joints exhibit a range of distinctive properties. Notably, CoSn3 nanocrystals dissolve in Sn during the reflow process, thereby lowering the supercooling required for Sn nucleation. Consequently, Sn crystals grow in six-fold cyclic twins. Additionally, the dissolution of Co atoms in Sn leads to a reduced solubility of Cu atoms in Sn, consequently lowering the supercooling required for the nucleation of Cu6Sn5. Simultaneously, this phenomenon promotes the nucleation of Cu6Sn5, resulting in a considerable precipitation of Cu6Sn5 nanoparticles within the joints. Therefore, the mechanical properties of the joints are significantly enhanced, leading to a notable 20% increase in shear strength. Furthermore, the presence and distribution of Co elements within Sn induce changes in the growth pattern of interfacial Cu6Sn5. The growth process of Cu6Sn5 is dominated by the interfacial reaction, leading to its growth in a faceted shape. During the aging process, the dissolution of Co elements in Sn impedes the continuous growth of Cu6Sn5 at the interface, causing Cu6Sn5 to be distributed in the form of islands inside the joint. Remarkably, elemental Co acts as an inhibitor for the development of Cu3Sn and reduces the occurrence of Kirkendall voids.

The broadband emission of Cr3+-doped CaY2Mg2Ge3O12 and its applications for NIR detectors.

A phosphor-converted light-emitting diode (pc-LED) is a prime light source in smart broadband near-infrared (NIR) spectroscopy. The performance of NIR pc-LEDs crucially depends on the employed NIR luminescent materials. In this study, we synthesized a novel high-efficiency broadband NIR phosphor, CaY2Mg2Ge3O12:Cr3+ (CYMG:Cr3+). Under 450 nm excitation, CYMG:Cr3+ exhibited remarkable broadband NIR emission from 650 to 900 nm with a full width at half maximum (FWHM) of 115 nm. Within the CYMG lattice, the Cr3+ ion occupies Ca/Y sites in the dodecahedron Ca/YO8 and Mg sites in the octahedron MgO6, giving rise to two distinct Cr3+ luminescence centers. Remarkably, the emission at 100 °C remained at 92% of its room temperature intensity and 81% at 150 °C, showcasing its exceptional thermal stability. The internal quantum efficiency (IQE) reached an impressive 81.1%, with an activation energy ΔE of 0.324 eV. Furthermore, we integrated the CYMG:Cr3+ phosphor with a commercial 450 nm blue chip to fabricate a micro NIR pc-LED, which exhibited stable NIR emission across different driving currents, with a NIR output power of 49.65 mW@400 mA and a photoelectric conversion efficiency of 10.52% at 20 mA. All findings highlight CYMG:Cr3+ as a stable and efficient broadband luminescent material for high-performance NIR LEDs.

Corrigendum: miR-766-3p targeting BCL9L suppressed tumorigenesis, epithelial-mesenchymal transition, and metastasis through the ß-catenin signaling pathway in osteosarcoma cells.

[This corrects the article DOI: 10.3389/fcell.2020.594135.].

Regulating steric hindrances of perylenediimide to construct NIR photothermal J-aggregates with a large red-shift.

Perylene diimide (PDI)-based photothermal agents (PTAs) possess excellent stability and high photothermal conversion efficiency. However, developing PDIs with strong near-infrared absorption under biological conditions remains a challenge. In this study, we introduce a novel approach to facilitate the formation of J-aggregate-based PTAs with significantly red-shifted absorption by modulating steric hindrances of PDIs. PDIA, featuring larger steric hindrances at the bay position and smaller steric hindrances at the imide position, self-assembles into J-aggregates which exhibit a remarkable red-shift of over 100 nm. After encapsulation by DPSE-PEG, PDIA nanoparticles (PDIA-NPs) demonstrated a uniform and stable size, while retaining their significant red-shift. In vitro experiments demonstrated the great potential of PDIA-NPs in photothermal therapies for tumors and thrombi under 808 nm laser irradiation. This research provides valuable insights into the design of stable J-aggregates based on PDIs suitable for biological applications, paving the way for the development of more effective PTAs.

Synthesis and Atomic Transport of CoSn3 NanoIMC by In Situ TEM.

In order to optimize the interfacial properties by adding Co to the bumps of copper pillars and to overcome the strong tendency of Co to oxidize, an intermetallic compound (IMC) "capsule" was developed for the purpose of transporting elements through the intermetallic compound. In this study, we present a comprehensive analysis of the transformation process of CoSn2 nanoparticles into CoSn3 at the nanoscale using in situ heating transmission electron microscopy (TEM). The experimental results reveal that CoSn2 nanoparticle growth occurs through polymerization, whereas CoSn3 nanoparticle formation relies on the reaction between CoSn2 and Sn. During the initial stages of the reaction, Co dissolves and diffuses into Sn, leading to the nucleation and growth of CoSn2 in Sn via Ostwald ripening. As the input energy increases, vacancies in CoSn2 drive a reaction at the Sn/CoSn2 interface, resulting in the generation of CoSn3. In this process, Sn nanoparticles enter the CoSn2 structure through the "Anti Structure Bridge (ASB) mechanism" to fill vacancies. Following the codeposition process, CoSn3 nanoparticles were successfully plated within the Sn layer of the Cu-pillar bumps. Upon reflow heating, the CoSn3 nanoparticles exhibited a preference for precipitating the vacant sites within the Sn layer. This process facilitated the release of Co atoms from CoSn2, enabling their diffusion throughout the entire Sn layer.

Non-contact thermometer behavior of (Y0.5In0.5)2O3:Yb3+,Er3+ solid solution.

Oxides are physically and chemically stable. Non-contact thermometer-Yb3+-Er3+ ions co-doped solid solution (Y0.5In0.5)2O3, is prepared by the regular solid method. The structural results obtained by XRD indicate that a pure phase solid solution (Y0.5In0.5)2O3 has been obtained. The solid solution (Y0.5In0.5)2O3 has a similar crystal structure, especially Y2O3 and In2O3 with the same space group (Ia3̄). Green emission from 500 to 600 nm is due to Er3+ 4f-4f transitions: 4S3/2 → 4I15/2 at 567 nm and 2H11/2 → 4I15/2 at 528 nm. Red emissions from 630 to 720 nm are attributed to Er3+: 4F9/2 → 4I15/2. UC luminescence changes greatly with laser diode power and Er3+ and Yb3+ content. Furthermore, the two-photon process is confirmed to be dominant between Yb3+ and Er3+ in oxide solid solution (Y0.5In0.5)2O3. Optical temperature sensitivity is also investigated systematically in order to explore the application of the oxide solid solution (Y0.5In0.5)2O3. The temperature-dependent green fluorescence at 528 and 567 nm was investigated with the range of 313-573 K. 0.316% K-1 is the maximum absolute sensitivity at 503 K, which is higher than most Yb3+/Er3+ co-doped systems. In addition, the solid solution (Y0.5In0.5)2O3:Yb3+,Er3+ has better thermal stability and stronger UC emission than a simple substance with excellent temperature sensing performance. It indicates that Yb3+-Er3+ ions co-doped (Y0.5In0.5)2O3 solid solution is a good candidate for optical temperature sensing.

Prognostic nomogram for glioblastoma (GBM) patients presenting with distant extension: a seer-based study.

BACKGROUND: Glioblastoma (GBM) with distant extension is rarely reported. We retrieved the data of GBM patients from the SEER database to identify the prognostic factors of GBM with distant extension and constructed a nomogram to predict the overall survival (OS) of these patients. METHODS: The data of GBM patients between 2003 and 2018 were retrieved from the SEER Database. 181 GBM patients with distant extension were randomly divided into the training cohort (n = 129) and the validation cohort (n = 52) at a ratio of 7:3. The prognostic factors associated with the OS of the GBM patients were identified through univariate and multivariate cox analyses. A nomogram was constructed based on the training cohort to predict OS, and its clinical value was verified using the validation cohort data. RESULTS: Kaplan-Meier curves showed that the prognosis was significantly worse for GBM patients with distant extension than GBM patients without distant extension. Stage (GBM patients with distant extension) was independent prognostic factor of survival. Multivariate Cox analyses demonstrated that age, surgery, radiotherapy and chemotherapy were independent risk factors for OS of GBM patients presenting with distant extension. The C-indexes of the nomogram for predicting OS were 0.755 (95% CI 0.713-0.797) and 0.757 (95% CI 0.703-0.811) for the training and validation cohorts, respectively. The calibration curves of both cohorts showed good consistency. The area under the curve (AUC) for predicting 0.25-year, 0.5-year and 1-year OS in the training cohort were 0.793, 0.864 and 0.867, respectively, and that in the validation cohort were 0.845, 0.828 and 0.803, respectively. The decision curve analysis (DCA) curves showed that the model to predict the 0.25-year, 0.5-year and 1-year OS probabilities was good. CONCLUSION: Stage (GBM patients with distant extension) is independent prognostic factor for GBM patients. Age, surgery, radiotherapy and chemotherapy are independent prognostic factors for GBM patients presenting with distant extension, and the nomogram based on these factors can accurately predict the 0.25-year, 0.5-year and 1-year OS of these patients.

Construction of ceRNA regulatory networks for osteoporosis.

Osteoporosis increases the risk of fracture. Improving the diagnosis and treatment of osteoporosis has clinical applications. The differentially expressed genes (DEcircRs, DEmRs, DEmiRs) of osteoporotic patients and controls were analyzed using the GEO database, and enrichment analysis of DEmRs was performed. circRNAs and mRNAs, which were predicted to have a target relationship with DEmRs, were obtained to compare competing endogenous RNA (ceRNA) regulatory networks by comparison with differentially expressed genes. Molecular experiments were utilized to validate the expression of genes within the network. The interactions between genes within the ceRNA network were validated by luciferase reporter assays. Following overexpression of circ_0070304 in bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of the cells was assessed by Alizarin Red staining. A total of 110 intersectional DEmRs between patients with osteoporosis and controls from GSE35958 and GSE56815, which were mainly enriched in estrogen, the thyroid hormone signaling pathway, and adherens junctions were identified. A ceRNA network [circ_0070304/miR­183­5p/ring finger and CCCH­type domains 2 (RC3H2)] was then constructed. Circ_0070304 acted as a sponge for miR­183­5p and regulated RC3H2 expression. Overexpression of circ_0070304 upregulated ROCK1 and induced osteogenic differentiation. The ceRNA regulatory network that was obtained is expected to be a new target for osteoporosis treatment and to provide new insights into the diagnosis and treatment of osteoporosis in greater depth.

Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome.

Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the pairwise motion of distal chromosomal elements such as enhancers and promoters is essential and necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output while systematically varying the genomic separation between these two DNA loci. Our analysis reveals the coexistence of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation leading to long-ranged correlations. Thus, encounter times of DNA loci are much less dependent on genomic distance than predicted by existing polymer models, with potential consequences for eukaryotic gene expression.

Targeting the KRT16-vimentin axis for metastasis in lung cancer.

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

An optimal selection method for exterior design schemes of subway trains based on multi-level gray relational analysis.

To make appropriate decisions in the evaluation phase of the exterior design of subway trains, an optimal selection method was proposed based on multi-level gray relational analysis. The exterior design factors of subway trains were analyzed to construct an index system for design evaluation. The significance of each index was compared through an analytic hierarchy process. The correlation coefficient of each index in the plan was calculated through gray relational analysis to obtain the weighted correlation degree of each design scheme. The optimal selection of the exterior design of Guangzhou Metro Line 6 in China was considered as an example. Four types of subjects were recruited: professional designers, students majoring in design, subway train design experts, and subway passengers in Guangzhou. The weight of each index in the evaluation system was calculated using questionnaire scoring. Virtual simulation software was applied to evaluate the human factors related to each scheme. The indices in each plan were then scored to calculate the correlation coefficient and the overall correlation degree; and finally, the optimal selection was obtained. The results showed that it was practical to evaluate and optimize the exterior design of subway trains based on multi-level gray relational analysis. In the evaluation index system, the weights of technology, human factors, aesthetics, and culture were 0.517, 0.297, 0.099, and 0.087, respectively, which showed that technology had the greatest impact on the system, while human factors, aesthetics, and culture were useful complements. Our results showed that Design Scheme 1 was unsuitable as an optimization scheme due to the high escape window. Meanwhile, Design Scheme 2 was optimal overall, from a technical perspective. Design Scheme 3 was the best in terms of the escape window index (a human factor). Design Schemes 3 and 4 were optimally assessed from aesthetic and cultural perspectives. This study is conducive to the optimization of the exterior design of subway trains, can be used to inform design iteration, and provides a reference for the optimal selection of design schemes for other urban rail trains.