Association between vertebral endplate defects and patient-reported symptoms: an immunohistochemical study investigating the COX-2/PGE-2/EP-4 axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into defect and non-defect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the defect group and non-defect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of non-defect group (52.5±7.7 vs. 57.2±9.1. p=.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than non-defect group (38.5% vs. 11.1%, p<.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs. 33.3%, p<.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs. 4.9±1.6, p<.001) and ODI scores (62.9±10.7 vs. 45.2±14.8, p<.001) than non-defect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in defect and non-defect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<0.001), PGE-2 (r=0.611; r=0.640, p both<.001), and EP-4 (r=0.643; r=0.563, p both<.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048-2.171], p=0.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106-1.508], p=.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], p=.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

Simulation and Experimental Study on the Effect of Superheat on Solidification Microstructure Evolution of Billet in Continuous Casting.

The control of the solidification structure of a casting billet is directly correlated with the quality of steel. Variations in superheat can influence the transition from columnar crystals to equiaxed crystals during the solidification process, subsequently impacting the final solidification structure of the billet. In this study, a model of microstructure evolution during billet solidification was established by combining simulation and experiment, and the dendrite growth microstructure evolution during billet solidification under different superheat was studied. The results show that when the superheat is 60 K, the complete solidification time of the casting billet from the end of the 50 mm section is 252 s, when the superheat is 40 K, the complete solidification time of the casting billet is 250 s, and when the superheat is 20 K, the complete solidification time of the casting billet is 245 s. When the superheat is 20 K, the proportion of the equiaxed crystal region is higher-the highest value is 53.35%-and the average grain radius is 0.84556 mm. The proportion of the equiaxed crystal region decreases with the increase of superheat. When the superheat is 60 K, the proportion of the equiaxed crystal region is the lowest-the lowest value is 46.27%-and the average grain radius is 1.07653 mm. Proper reduction of superheat can obviously reduce the size of equiaxed crystal, expand the area of equiaxed crystal and improve the quality of casting billet.

Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KITW-SH/W-SH) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.

UVR8-TCP4-LOX2 module regulates UV-B tolerance in Arabidopsis.

The phytohormone jasmonate (JA) coordinates stress and growth responses to increase plant survival in unfavorable environments. Although JA can enhance plant UV-B stress tolerance, the mechanisms underlying the interaction of UV-B and JA in this response remain unknown. In this study, we demonstrate that the UV RESISTANCE LOCUS 8 - TEOSINTE BRANCHED1, Cycloidea and PCF 4 - LIPOXYGENASE2 (UVR8-TCP4-LOX2) module regulates UV-B tolerance dependent on JA signaling pathway in Arabidopsis thaliana. We show that the nucleus-localized UVR8 physically interacts with TCP4 to increase the DNA-binding activity of TCP4 and upregulate the JA biosynthesis gene LOX2. Furthermore, UVR8 activates the expression of LOX2 in a TCP4-dependent manner. Our genetic analysis also provides evidence that TCP4 acts downstream of UVR8 and upstream of LOX2 to mediate plant responses to UV-B stress. Our results illustrate that the UV-B-dependent interaction of UVR8 and TCP4 serves as an important UVR8-TCP4-LOX2 module, which integrates UV-B radiation and JA signaling and represents a new UVR8 signaling mechanism in plants.

Attention-based investigation and solution to the trade-off issue of adversarial training.

Adversarial training has become the mainstream method to boost adversarial robustness of deep models. However, it often suffers from the trade-off dilemma, where the use of adversarial examples hurts the standard generalization of models on natural data. To study this phenomenon, we investigate it from the perspective of spatial attention. In brief, standard training typically encourages a model to conduct a comprehensive check to input space. But adversarial training often causes a model to overly concentrate on sparse spatial regions. This reduced tendency is beneficial to avoid adversarial accumulation but easily makes the model ignore abundant discriminative information, thereby resulting in weak generalization. To address this issue, this paper introduces an Attention-Enhanced Learning Framework (AELF) for robustness training. The main idea is to enable the model to inherit the attention pattern of standard pre-trained model through an embedding-level regularization. To be specific, given a teacher model built on natural examples, the embedding distribution of teacher model is used as a static constraint to regulate the embedding outputs of the objective model. This design is mainly supported with that the embedding feature of standard model is usually recognized as a rich semantic integration of input. For implementation, we present a simplified AELFs that can achieve the regularization with single cross entropy loss via the parameter initialization and parameter update strategy. This avoids the extra consistency comparison operation between embedding vectors. Experimental observations verify the rationality of our argument, and experimental results demonstrate that it can achieve remarkable improvements in generalization under the high-level robustness.

Urolithin B reduces cartilage degeneration and alleviates osteoarthritis by inhibiting inflammation.

Osteoarthritis is the most prevalent degenerative joint disease reported worldwide. Conventional treatment strategies mainly focus on medication and involve surgical joint replacement. The use of these therapies is limited by gastrointestinal complications and the lifespan of joint prostheses. Hence, safe and efficacious drugs are urgently needed to impede the osteoarthritis progression. Urolithin B, a metabolite of ellagic acid in the gut, exhibits anti-inflammatory and antioxidant properties; however, its role in osteoarthritis remains unclear. In this study, we demonstrated that urolithin B efficiently inhibits the inflammatory factor-induced production of matrix metalloproteinases (MMP3 and MMP13) in vitro and upregulates the expression of type II collagen and aggrecan. Urolithin B alleviates cartilage erosion and osteophyte formation induced by anterior cruciate ligament transections. Moreover, urolithin B inhibits the activation of the NF-κB pathway by reducing the phosphorylation of Iκb-α and the nuclear translocation of P65. In summary, urolithin B significantly inhibits inflammation and alleviates osteoarthritis. Hence, urolithin B can be considered a potential agent suitable for the effective treatment of osteoarthritis in the future.

FATP2 regulates Osteoclastogenesis by increasing lipid metabolism and ROS production.

Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation while only slightly affecting osteoblasts (OBs). In pathological models of bone loss induced by LPS or OVX, in vivo treatment with Lipofermata was able to rescue the loss of bone mass by inhibiting OC differentiation. RNA sequencing (RNA-seq) revealed that Lipofermata reduced fatty acid ß-oxidation and inhibited energy metabolism, while regulating reactive oxygen species (ROS) metabolism to decrease ROS production, ultimately inhibiting OC differentiation. Treatment with Lipofermata, either in vivo or in vitro, effectively rescued the overactivation of OCs, indicating that FATP2 regulated OC differentiation by modulating fatty acid uptake and energy metabolism. These findings suggested that targeting FATP2 may represent a promising therapeutic approach for pathological osteoporosis.

The inhibition of osteoclastogenesis by Lipofermata, a FATP2 inhibitor, was achieved through the reprogramming of energy metabolism and regulation of ROS levels. In both pathological bone loss and HFD-induced osteoporosis models, the expression levels of FATP2 were significantly upregulated and Lipofermata demonstrated potential therapeutic effects in the pathological bone loss model.

Influence of serial intravitreal injections on measures of dry eye: A systemic review and meta-analysis.

PURPOSE: The aim of this study was to evaluate the long-term effects of serial intravitreal injections (IVI) on measures of dry eye. METHODS: The PubMed, EMBASE, and Cochrane databases were searched according to the PROSPERO protocol (CRD42023455727). Studies evaluating the influence of serial IVI on the ocular surface compared with untreated fellow eyes were included. The measures of dry eye after IVI were used as outcome variables. The results are presented as mean difference (MD) with a corresponding 95% confidence interval (CI). RESULTS: A total of 4 studies with 259 participants were included in this meta-analysis. Significant increases in ocular surface disease index (OSDI) scores (MD 10.26, 95 % CI 5.05 to 15.46, p ＜ 0.01) and tear film osmolarity (TOsm; MD 4.40, 95 % CI 0.87 to 7.92, p = 0.01) were observed in the IVI treated eyes compared to the untreated fellow eyes. There was no significant difference between the groups with respect to fluorescein tear film break-up time (TBUT; p = 0.05), average non-invasive tear film break-up time (NITBUT; p = 0.94), first NITBUT (p = 0.78) and Schirmer test (p = 0.94). CONCLUSION: Repeated IVI of anti-VEGF agents with preoperative povidone-iodine application was associated with increased OSDI scores and TOsm, while no significant difference was found in fluorescein TBUT, average NITBUT, first NITBUT and Schirmer test. The ocular surface may partially recover after the procedures, but IVI still has deleterious effects on the ocular surface.

Restrained Mitf-associated autophagy by Mulberroside A ameliorates osteoclastogenesis and counteracts OVX-Induced osteoporosis in mice.

Bone and mineral metabolism homeostasis accounts for the maintenance of normal skeletal remodeling. However, with aging and changes in hormone levels, over-activated osteoclasts disrupt homeostasis, induce osteoporosis, and even cause osteoporotic fractures, leading to an enormous economic burden. Despite the rapid development of pharmacological therapy for osteoporosis, safer and more effective treatments remain to be explored. Here, we demonstrate that Mulberroside A (Mul-A), a natural component extracted from mulberry bark and branches, effectively suppresses osteoclastogenesis in vitro and counteracts bone loss caused by ovariectomy (OVX). The mechanism underlying this effect involves the repression of autophagic flux during osteoclastogenesis by Mul-A, which can be attributed to the restrained expression of microphthalmia-related transcription factor (Mitf) and its nuclear translocation. Importantly, Mitf overexpression partially reverses the inhibitory effects of Mul-A on autophagy and osteoclastogenesis. Moreover, applying two autophagy agonizts, rapamycin and Torin 1, attenuates the osteoclastogenic regulatory role of Mul-A. Collectively, our study demonstrates that Mul-A damages osteoclast differentiation and ameliorates osteoporosis caused by estrogen deficiency by modulation of Mitf-associated autophagy, indicating its therapeutic potential against osteoporosis.

Multicargo-loaded inverse opal gelatin hydrogel microparticles for promoting bacteria-infected wound healing.

Nowadays, many strategies have been developed to design biomaterials to accelerate bacteria-infected wound healing. Here, we presented a new type of multicargo-loaded inverse opal hydrogel microparticle (IOHM) for regulating oxidative stress, antibiosis, and angiogenesis of the bacteria-infected wound. The methacrylate acylated gelatin (GelMA)-based inverse opal hydrogel microparticles (IOHMs) were obtained by using the colloidal crystal microparticles as templates, and fullerol, silver nanoparticles (Ag NPs), and vascular endothelial growth factor (VEGF) were loaded in IOHMs. The developed multicargo-loaded IOHMs displayed good size distribution and biocompatibility, and when they were applied in cell culture, bacteria culture, and animal experiments, they exhibited excellent anti-oxidative stress properties, antibacterial properties, and angiogenesis. These characteristics of the developed multicargo-loaded IOHMs make them ideal for bacteria-infected wound healing.

Numerical Simulation of Fluid Flow, Solidification, and Solute Distribution in Billets under Combined Mold and Final Electromagnetic Stirring.

In this study, a three-dimensional segmented coupled model for continuous casting billets under combined mold and final electromagnetic stirring (M-EMS, F-EMS) was developed. The model was verified by comparing carbon segregation in billets with and without EMS through plant experiments. The findings revealed that both M-EMS and F-EMS induce tangential flow in molten steel, impacting solidification and solute distribution processes within the billet. For M-EMS, with operating parameters of 250A-2Hz, the maximum tangential velocity (velocity projected onto the cross-section) was observed at the liquid phase's edge. For F-EMS, with operating parameters of 250A-6Hz, the maximum tangential velocity occurred at fl=0.7. Furthermore, F-EMS accelerated heat transfer in the liquid phase, reducing the central liquid fraction from 0.93 to 0.85. M-EMS intensified the washing effect of molten steel on the solidification front, resulting in the formation of negative segregation within the mold. F-EMS significantly improved the centerline segregation issue, reducing carbon segregation from 1.15 to 1.02. Experimental and simulation results, with and without EMS, were in good agreement, indicating that M+F-EMS leads to a more uniform solute distribution within the billet, with a pronounced improvement in centerline segregation.

Numerical and Experimental Study on Carbon Segregation in Shaped Billet of Medium Carbon Steel with Combined Electromagnetic Stirring.

Carbon segregation is the major and classical internal defect in the continuous casting process of carbon steel. Based on the combined electromagnetic stirring equipment for new billet in a steel plant, China, the influence of combined electromagnetic stirring (M-EMS + F-EMS) on the carbon segregation of 300 mm × 340 mm special-shaped billet was studied via numerical simulation and on-site industrialization tests. The Lorentz force and carbon solute distribution were simulated under different EMS parameters. The formation mechanism of the carbon segregation of medium carbon steel with different combined electromagnetic stirring processes was analyzed. The results show that: (1) with the combined action of "solute flushing" effect and gravity, the carbon concentration in the loose side of the medium carbon steel casting billet is gradually lower than the fixed side, while the carbon concentration on the fixed side gradually accumulates more; and (2) under the action of combined electromagnetic stirring, the segregation index of casting billet could be controlled to remain between 0.96-1.05 and shows an increasing change in solidification from the skin to the center. When the current and frequency of M-EMS are 250 A and 2.0 Hz and the F-EMS are 180 A and 8.0 Hz, the carbon segregation defects in the special-shaped (300 mm × 340 mm) casting billet can be significantly improved.

Vision-Based UAV Self-Positioning in Low-Altitude Urban Environments.

Unmanned Aerial Vehicles (UAVs) rely on satellite systems for stable positioning. However, due to limited satellite coverage or communication disruptions, UAVs may lose signals for positioning. In such situations, vision-based techniques can serve as an alternative, ensuring the self-positioning capability of UAVs. However, most of the existing datasets are developed for the geo-localization task of the objects captured by UAVs, rather than UAV self-positioning. Furthermore, the existing UAV datasets apply discrete sampling to synthetic data, such as Google Maps, neglecting the crucial aspects of dense sampling and the uncertainties commonly experienced in practical scenarios. To address these issues, this paper presents a new dataset, DenseUAV, that is the first publicly available dataset tailored for the UAV self-positioning task. DenseUAV adopts dense sampling on UAV images obtained in low-altitude urban areas. In total, over 27K UAV- and satellite-view images of 14 university campuses are collected and annotated. In terms of methodology, we first verify the superiority of Transformers over CNNs for the proposed task. Then we incorporate metric learning into representation learning to enhance the model's discriminative capacity and to reduce the modality discrepancy. Besides, to facilitate joint learning from both the satellite and UAV views, we introduce a mutually supervised learning approach. Last, we enhance the Recall@K metric and introduce a new measurement, SDM@K, to evaluate both the retrieval and localization performance for the proposed task. As a result, the proposed baseline method achieves a remarkable Recall@1 score of 83.01% and an SDM@1 score of 86.50% on DenseUAV. The dataset and code have been made publicly available on https://github.com/Dmmm1997/DenseUAV.

Simulation Study on the Influence of Different Molten Steel Temperatures on Inclusion Distribution under Dual-Channel Induction-Heating Conditions.

Impurity elimination in tundishes is an essential metallurgical function in continuous casting. If inclusions in a tundish cannot be effectively removed, their presence will have a serious impact on the quality of the bloom. As a result, this research investigates the locations of inclusion particles in a six-strand induction-heating tundish in depth, combining the flow, temperature, and inclusion trajectories of molten steel under electromagnetic fields. The results show that a pinch effect occurred in the induction-heating tundish, and a rotating magnetic field formed in the channel, with a maximum value of 0.158 T. The electromagnetic force was directed toward the center of the axis, and its numerical distribution corresponds to the magnetic flux density distribution, with a maximum value of 2.11 × 105 N/m3. The inclusion particles' movement speed accelerated as the molten steel's temperature rose, and their distribution in the channel was identical to the rotating flow field distribution. When the steel's temperature rose from 1750 K to 1850 K, the removal percentage of inclusion particles in the discharge chamber rose by 9.20%, the removal rate at the outlet decreased from 8.00% to 3.00%, and the adhesion percentage of inclusion particles in the channel decreased from 48.40% to 44.40%.

Construction of a Two-Dimensional GO/Ti3C2TX Composite Membrane and Investigation of Mg2+/Li+ Separation Performance.

Graphene oxide (GO) two-dimensional (2D) membranes with unique layer structures and tunable layer spacing have special advantages and great potential in the field of water treatment. However, GO membranes face the issues of weak anti-swelling ability as well as poor permeability. We prepared GO/Ti3C2TX 2D composite membranes with 2D/2D structures by intercalating Ti3C2TX nanosheets with slightly smaller sizes into GO membranes. Ti3C2TX intercalation can effectively expand the layer spacing of GO, thereby substantially enhancing the flux of the composite membrane (2.82 to 6.35 L·m-2·h-1). Moreover, the GO/Ti3C2TX composite membrane exhibited a good Mg2+/Li+ separation capability. For the simulated brine, the separation factor of M2 was 3.81, and the salt solution flux was as high as 5.26 L·m-2·h-1. Meanwhile, the incorporation of Ti3C2TX nanosheets significantly improved the stability of GO/Ti3C2TX membranes in different pH environments. This study provides a unique insight into the preparation of highly permeable and ion-selective GO membranes.

From fetal tendon regeneration to adult therapeutic modalities: TGF-ß3 in scarless healing.

Tendon injuries are common disorders that can significantly impact people's lives. Unfortunately, the limited regenerative ability of tendons results in tissue healing in a scar-mediated manner. The current therapeutic strategies fail to fully recover the functions of the injured tendons, and as such, the conception of 'scarless healing' has gained prominent attention in the field of regenerative medicine. Interestingly, injured fetal tendons possess the capability to heal through regeneration, which builds an ideal blueprint for adult tendon regeneration. Studies have shown that fetal biochemical cues have the potential to improve adult tendon healing. Here we review the biological factors that contribute to fetal tendon regeneration and how manipulation of these biochemical cues in the adult tendon healing process could achieve regeneration.

We reviewed the biological factors that contribute to fetal tendon regeneration and how manipulation of these biochemical cues in the adult tendon healing process could achieve regeneration. The results showed that inflammation and TGF-ß level are the main elements involved in fetal tendon regeneration. Experimental manipulation of these biochemical cues in the adult tendon healing process demonstrated that although the blockade of TGF-ß1, TGF-ß2 and inflammation reduced scar tissue in adult tendon healing, this inhibition also destroyed the mechanical properties of the tendons. An effective alternative is regulating the specific downstream profibrotic effectors of both TGF-ß1 and inflammation, which is preferable to those that completely inhibit these factors. Finally, TGF-ß3 is a master regulator allowing a shift from adult scar healing to scarless healing, and the administration of TGF-ß3 is a viable strategy to promote adult regenerative healing. In terms of mechanisms, TGF-ß3 can activate Smad7 and inhibit the JNK/c-Jun signaling pathway to promote tendon regenerative healing.

Differential Gene Expression Profiles and Pathways Highlight the Role of Osteoimmunology in Neurofibromatosis Type 1-Related Dystrophic Scoliosis With Osteopenia.

STUDY DESIGN: Microarray approach and integrated gene network analysis. OBJECTIVE: To explore the differential genetic expression profile, Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in human trabecular bone (HTB)-derived cells of dystrophic scoliosis secondary to neurofibromatosis type 1 (DS-NF1) and compare these to normal controls. SUMMARY OF BACKGROUND DATA: The pathogenesis of DS-NF1 and the accompanying generalized osteopenia remain unclear. We hypothesized that HTBs may play a significant role in the etiology and pathogenesis of DS-NF1. MATERIALS AND METHODS: Microarray analysis was used to identify differentially expressed genes of HTBs from patients with DS-NF1 compared with those from healthy individuals. Functional and pathway enrichment analysis were implemented through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Then, the "search tool for the retrieval of interacting genes/proteins" database, Cytoscape, and "Molecular Complex Detection" were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified through module analysis. Six potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. RESULTS: Bioinformatic analysis revealed that there are 401 previously unrecognized differentially expressed genes (238 up and 163 downregulated genes) in HTBs from patients with DS-NF1, and they were mainly enriched in terms of immune response, type-I interferon (IFN) signaling, TNF signaling pathway and etinoic acid inducible gene I-like receptor signaling pathway. Five hub genes, including signal transducer and activator of transcription 1, 2'-5'-oligoadenylate synthetase-like, IFN induced with helicase C domain 1, IFN regulatory factor 7, and MX dynamin-like GTPase 1 were identified through PPI network, which were mainly enriched in terms of Jak-STAT and etinoic acid inducible gene I-like receptor signaling pathway. An independently dysregulated protein cluster containing CCL2, CXCL1, CXCL3, CX3CL1, TLR1 , and CXCL12 was also identified through the PPI network. This indicated that the upper abnormally expressed genes may play essential roles in DS-NF1 pathogenesis and accompanied osteopenia. CONCLUSION: Six key genes were identified in the progression of DS-NF1-related osteopenia. Immune response might play a key role in the progression of osteopenia, whereas a CXCL12 -mediated osteogenic effect might play a protective role.

The Removal of Inclusions with Different Diameters in Tundish by Channel Induction Heating: A Numerical Simulation Study.

The quality of the bloom will be impacted by the non-metallic impurities in the molten steel in the tundish, which will reduce the plasticity and fatigue life of the steel. In this research, a mathematical model of a six-flow double-channel T-shaped induction heating tundish was established, the effects of induction heating conditions on the removal of inclusions in the tundish were investigated, and the impact of various inclusion particle sizes on the removal effect of inclusions under induction heating was explored. The results show that the Residence Time Distribution (RTD) curve produced through numerical simulation and physical simulation is in good agreement. The reduction of inclusion particles in the channel is made affordable by the dual-channel induction heating technique. As the diameter of inclusion particles increases from 10 µm to 50 µm, the probability of inclusion particles being removed from the channel gradually decreases from 70.9% to 56.1%.

Numerical and Experimental Study on Carbon Segregation in Square Billet Continuous Casting with M-EMS.

Electromagnetic stirring (M-EMS) has been extensively applied in continuous casting production to reduce the quality defects of casting billets. To investigate the effect of continuous casting electromagnetic stirring on billet segregation, a 3D multi-physics coupling model was established to simulate the internal heat, momentum, and solute transfer behavior, to identify the effect of M-EMS on the carbon segregation of a continuous casting square billet of 200 mm × 200 mm. The results show that M-EMS can move the high-temperature zone upward, which is favorable for the rapid solidification of the billet, and can promote the rotational flow of the molten steel in the horizontal direction. When the electromagnetic stirring current is varied in the range of 0-500 A, the degree of carbon segregation first decreases and then increases, with the best control of segregation at 300 A. In the frequency range of 3-5 Hz, the degree of carbon segregation degree increases with frequency. Meanwhile, the simulation and experimental results show that 3 Hz + 300 A is the best electromagnetic stirring parameter for improving the carbon segregation of casting billets with a size of 200 mm × 200 mm. So, a reasonable choice of the M-EMS parameters is crucial for the quality of the billet.

The investigation of interaction and chaperon-like activity of α-synuclein as a protein in pathophysiology of Parkinson's disease upon direct interaction with tectorigenin.

Analyzing the therapeutic potential of a therapeutic biomolecule requires an understanding of how it may interact with proteins and modify their corresponding functions. α-Synuclein is a protein which is widely involved in the pathogenesis of Parkinson's disease (PD) and shows chaperon-like activity. We have selected tectorigenin, a most common methoxyisoflavone extracted from plants, among therapeutic bioactive molecules that are documented to have different therapeutic effects. Herein, we aimed to explore how tectorigenin interacts with α-synuclein in vitro by mimicking the physiological environment. Spectroscopic as well as theoretical studies including molecular docking simulation, were used to examine the effects of tectorigenin on the conformation and dynamics of α-synuclein. It was shown that tectorigenin is able to quench the protein emission spectra relied on a mixed static-dynamic quenching mechanism. Furthermore, it was displayed that tectorigenin binding to α-synuclein leads to microenvironmental changes in the tertiary structure of protein, however the protein's secondary structure was almost unchanged. It was also deduced that tectorigenin results in thermal stability of α-synuclein structure, evidenced by less perturbation of α-synuclein secondary structure following elevation of temperature in the presence of tectorigenin relative to that of free form. Molecular docking simulation demonstrated that non-covalent reactions, mainly hydrogen bonds, had a key role in the interaction and stabilization of α-synuclein in the presence of tectorigenin. Moreover, chaperon-like activity of α-synuclein was improved in the presence of tectorigenin against two model proteins, ßL-crystallin and catalase. The findings showed that tectorigenin can lead to stabilization of α-synuclein, which may be used as a therapeutic agent in prevention of neurodegenerative diseases.