Rewritable printing of ionic liquid nanofilm utilizing focused ion beam induced film wetting.

Manipulating liquid flow over open solid substrate at nanoscale is important for printing, sensing, and energy devices. The predominant methods of liquid maneuvering usually involve complicated surface fabrications, while recent attempts employing external stimuli face difficulties in attaining nanoscale flow control. Here we report a largely unexplored ion beam induced film wetting (IBFW) technology for open surface nanofluidics. Local electrostatic forces, which are generated by the unique charging effect of Helium focused ion beam (HFIB), induce precursor film of ionic liquid and the disjoining pressure propels and stabilizes the nanofilm with desired patterns. The IBFW technique eliminates the complicated surface fabrication procedures to achieve nanoscale flow in a controllable and rewritable manner. By combining with electrochemical deposition, various solid materials with desired patterns can be produced.

Enhancing the Ag-loading capacity on Ti3C2Tx sheets as hybrid fillers to form composite coatings with excellent antibacterial properties.

The settlement of microorganisms is an unwanted process in various practical fields, where also the first attaching microorganisms could promote other bacterial adhesion, causing an acceleration of bioaccumulation on the solid surface and damage to the surface functions. Developing an advanced composite coating with anti-microorganism attachment features is still a big challenge, and the critical element in any such method is to find an efficient functional agent for use in the coating system that could extend the service period. MXenes have received increasing attentions owing to their unique layer structure and large specific surface area. Increasing studies have been devoted to the development of MXene/polymer composites with creatively designed structures to realize various specific functions. Herein, two-dimensional (2D) transition metal carbide material MXene as a carrier was etched and decorated with cellulose to enhance the anchor points to grasp functional Ag nanoparticles via a simple method. The MXene nanosheets (Ti3C2Tx) were modified by cellulose to graft hydroxy groups on their surface, and then they were incorporated into silver nanoparticles (Ag NPs). The results showed that the cellulose could increase the loading content of the Ag NPs on the MXene surface, and also could act as a stabilized material to form the composite filler MXene@cellulose@Ag NPs (MAC), which could serve as a functional agent. Furthermore, the obtained product MAC filler exhibited excellent dispersibility and stability among all the tested fillers (MXene and MA), and it could help avoid aggregation and promote homogenous dispersal in the coating network. Besides, MAC displayed outstanding antibacterial activities against E. coli and S. aureus at the same concentration among all the fillers. When the filler was embedded into the coating system, the composite coating PCB-MAC possessed abundant active Ag+ ions released by the Ag NPs, which could work against bacterial growth and achieve a favorable antibacterial inhibition effect. Therefore, we believe that the active MAC filler maintained high antibacterial efficiency, evincing its potential as a desirable agent for obtaining an excellent anti-adhesive behavior in numerous broad applications, such as the environment field or medical area.

Immune-related gene IL17RA as a diagnostic marker in osteoporosis.

Objectives: Bone immune disorders are major contributors to osteoporosis development. This study aims to identify potential diagnostic markers and molecular targets for osteoporosis treatment from an immunological perspective. Method: We downloaded dataset GSE56116 from the Gene Expression Omnibus database, and identified differentially expressed genes (DEGs) between normal and osteoporosis groups. Subsequently, differentially expressed immune-related genes (DEIRGs) were identified, and a functional enrichment analysis was performed. A protein-protein interaction network was also constructed based on data from STRING database to identify hub genes. Following external validation using an additional dataset (GSE35959), effective biomarkers were confirmed using RT-qPCR and immunohistochemical (IHC) staining. ROC curves were constructed to validate the diagnostic values of the identified biomarkers. Finally, a ceRNA and a transcription factor network was constructed, and a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to explore the biological functions of these diagnostic markers. Results: In total, 307 and 31 DEGs and DEIRGs were identified, respectively. The enrichment analysis revealed that the DEIRGs are mainly associated with Gene Ontology terms of positive regulation of MAPK cascade, granulocyte chemotaxis, and cytokine receptor. protein-protein interaction network analysis revealed 10 hub genes: FGF8, KL, CCL3, FGF4, IL9, FGF9, BMP7, IL17RA, IL12RB2, CD40LG. The expression level of IL17RA was also found to be significantly high. RT-qPCR and immunohistochemical results showed that the expression of IL17RA was significantly higher in osteoporosis patients compared to the normal group, as evidenced by the area under the curve Area Under Curve of 0.802. Then, we constructed NEAT1-hsa-miR-128-3p-IL17RA, and SNHG1-hsa-miR-128-3p-IL17RA ceRNA networks in addition to ERF-IL17RA, IRF8-IL17RA, POLR2A-IL17RA and ERG-IL17RA transcriptional networks. Finally, functional enrichment analysis revealed that IL17RA was involved in the development and progression of osteoporosis by regulating local immune and inflammatory processes in bone tissue. Conclusion: This study identifies the immune-related gene IL17RA as a diagnostic marker of osteoporosis from an immunological perspective, and provides insight into its biological function.

Study of a Novel Fluorine-Containing Polyether Waterborne Polyurethane with POSS as a Cross-Linking Agent.

Waterborne polyurethane are more eco-friendly materials due to lower volatile organic compounds (VOCs, mainly isocyanates) content than the alternative materials. However, these rich hydrophilic groups polymers have not yet reached good mechanical properties, durability and hydrophobicity behaviors. Therefore, hydrophobic waterborne polyurethane has become a research hotspot, attracting significant attention. In this work, firstly, a novel fluorine-containing polyether P(FPO/THF) was synthesized by cationic ring-opening polymerization of 2-(2,2,3,3-tetrafluoro-propoxymethyl)-oxirane (FPO) and tetrahydrofuran (THF). Secondly, fluorinated polymer P(FPO/THF), isophorone diisocyanate (IPDI) and hydroxy-terminated polyhedral oligomeric silsesquioxane (POSS-(OH)8) were used to prepare a new fluorinated waterborne polyurethane (FWPU). Hydroxy-terminated POSS-(OH)8 was used as a cross-linking agent, while dimethylolpropionic acid (DMPA) and triethylamine (TEA) were used as a catalyst. Four kinds of waterborne polyurethanes (FWPU0, FWPU1, FWPU3, FWPU5) were obtained by adding different contents of POSS-(OH)8 (0%, 1%, 3%, 5%). The structures of the monomers and polymers were verified by 1H NMR and FT-IR, and the thermal stabilities of various waterborne polyurethanes were analyzed by thermogravimetric analyzer (TGA) and differential scanning calorimetry (DSC). As the results, the thermal analysis showed that the FWPU performed the good thermal stability and the glass transition temperature could reach at about -50 °C. The FWPU1 film exhibited that the elongation at break was 594.4 ± 3.6% and the tensile strength at break was 13.4 ± 0.7 MPa, elucidating that the FWPU1 film developed the excellent mechanical properties relative to the alternative FWPUs. Further, the FWPU5 film performed the promising properties, including the higher surface roughness of FWPU5 film (8.41 nm) obtained by the atomic force microscope (AFM) analysis, and the higher value of water contact angle (WCA) at 104.3 ± 2.7°. Those results illustrated that the novel POSS-based waterborne polyurethane FWPU containing a fluorine element could develop the excellent hydrophobicity and mechanical properties.

Comprehensive analysis of senescence-related genes and immune infiltration in intervertebral disc degeneration: a meta-data approach utilizing bulk and single-cell RNA sequencing data.

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD). Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs. Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils. Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies.

Electrically switched underwater capillary adhesion.

Developing underwater adhesives that can rapidly and reversibly switch the adhesion in wet conditions is important in various industrial and biomedical applications. Despite extensive progresses, the manifestation of underwater adhesion with rapid reversibility remains a big challenge. Here, we report a simple strategy that achieves strong underwater adhesion between two surfaces as well as rapid and reversible detachment in on-demand manner. Our approach leverages on the design of patterned hybrid wettability on surfaces that selectively creates a spatially confined integral air shell to preserve the water bridge in underwater environment. The overall adhesion strength can be multiplied by introducing multiple air shells and rapidly broken by disturbing the integrity of the protective air shell in response to the applied voltage on two surfaces. Our design can be constructed on the flexible substrate with hybrid wettability, which can be applied to non-conductive substrates and adapted to more complicated morphologies, extending the choice of underlying materials.

Efficacy of anterior-posterior decompression on thoracolumbar spine fracture with spinal cord injury and analysis of risk factors for postoperative deep vein thrombosis.

OBJECTIVE: To investigate the efficacy of anterior-posterior decompression on thoracolumbar spine fracture (TSF) and spinal cord injury (SCI), and assess hazard factors for postoperative deep vein thrombosis (DVT) through logistics regression. METHODS: A retrospective analysis was made on 130 patients with TSF and SCI admitted to our hospital between Jan 2018 and Jan 2020. Specifically, 72 were treated with anterior decompression (experimental group) and 58 were posterior decompression (control group). The intraoperative blood loss, procedure time, hospitalization, incision size, tactile and motor scores, injured vertebral body height, Cobb angle and complications were observed. Patients were grouped based on DVT occurrence. The risk factors were assessed through logistics regression. RESULTS: In comparison to experimental group, the intraoperative blood loss, procedure time and incision size in the control group were lower (P<0.05), while the hospitalization time was shorter (P<0.05). After treatment, the tactile and motor scores were improved 3 months after operation, and the experimental group was better (P<0.05). Additionally, injured vertebral body height and Cobb angle increased, and the experimental group was higher (P<0.05). Incidence of postoperative complications revealed no marked difference (P>0.05). Logistics regression analysis manifested that ASIA rating, diabetes, obesity and age were tied to postoperative DVT. CONCLUSION: Anterior decompression therapy can effectively improve the clinical outcome of patients with thoracolumbar spinal fractures and spinal cord injury on the improvement of tactile and motor functions, but posterior decompression is better than anterior surgery in terms of bleeding, incision length, operating time, and hospital stay. Surgical treatment needs to be selected according to the condition of patients. Furthermore, it was identified that ASIA rating, history of diabetes, obesity and age are risk factors affecting patients with postoperative lower extremity DVT.

Bubble energy generator.

Bubbles have been extensively explored as energy carriers ranging from boiling heat transfer and targeted cancer diagnosis. Yet, despite notable progress, the kinetic energy inherent in small bubbles remains difficult to harvest. Here, we develop a transistor-inspired bubble energy generator for directly and efficiently harvesting energy from small bubbles. The key points lie in designing dielectric surface with high-density electric charges and tailored surface wettability as well as transistor-inspired electrode configuration. The synergy between these features facilitates fast bubble spreading and subsequent departure, transforms the initial liquid/solid interface into gas/solid interface under the gating of bubble, and yields an output at least one order of magnitude higher than existing studies. We also show that the output can be further enhanced through rapid bubble collapse at the air/liquid interface and multiple bubbles synchronization. We envision that our design will pave the way for small bubble-based energy harvesting in liquid media.

Effective removal of hydrogen sulfide from landfill gases using a modified iron pentacarbonyl desulfurization agent and the desulfurization mechanism.

High-efficiency desulfurization is key to the recovery and use of landfill gases. In this study, a nano­iron oxide desulfurization agent modified from iron pentacarbonyl was prepared in n-decane (DE) and hexadecane (HE) by ultrasonic disruption without any supporting materials and its hydrogen sulfide removal ability and desulfurization mechanism were studied. The yield of the desulfurization agent was higher when HE was used as the solvent; however, the products generated by both solvents had the same crystal type and similar properties. The efficiency of the desulfurization agent was significantly improved at 150-200 °C, exceeding 90% at 150 °C with single sulfur production. The maximum sulfur adsorption capacity of the desulfurization agent produced after 3 h of DE ultrasonic treatment at 200 °C (DE3) was 492 mg/g (desulfurization efficiency = 97.33%), while that of the agent produced after 3 h of HE ultrasonic treatment at 250 °C (HE3) was 522 mg/g (desulfurization efficiency = 99.30%). The desulfurization reaction involved both chemical adsorption and catalytic decomposition and the catalytic decomposition reaction rate was lower than that of chemical adsorption. Therefore, the more FexSy produced in the chemical adsorption process, the better catalytic performance was.

Genetic diversity analysis of forty-three insertion/deletion loci for forensic individual identification in Han Chinese from Beijing based on a novel panel.

Due to the virtues of no stutter peaks, low rates of mutation, and short amplicon sizes, insertion/deletion (InDel) polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications (Wang et al., 2021). Herein, a self-developed panel of 43 InDel loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing (HCB) including 301 random healthy individuals. The lengths of amplicons at 43 InDel loci in this panel ranged from 87 to 199 bp, which indicated that the panel could be used as an effective tool to utilize highly degraded DNA samples for human identity testing. The loci in this panel were validated and performed well for forensic degraded DNA samples (Jin et al., 2021). The combined discrimination power (PD) and combined probability of exclusion (PE) values in this panel indicated that the 43 InDel loci could be used as the candidate markers in personal identification and parentage testing of HCB. In addition, population genetic relationships between the HCB and 26 reference populations from five continents based on 19 overlapped InDel loci were displayed by constructing a phylogenetic tree, principal component analysis (PCA), and population genetic structure analysis. The results illustrated that the HCB had closer genetic relationships with the Han populations from Chinese different regions.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1ß-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

Curcumin suppress inflammatory response in traumatic brain injury via p38/MAPK signaling pathway.

Traumatic brain injury (TBI) is a common disease worldwide with a high mortality and disability rate and is closely related to the inflammatory response. However, the molecular mechanisms during the pathophysiological responses are not completely understood. This study was conducted to investigate the protective effect of curcumin on TBI and the molecular mechanisms of the p38/MAPK signal pathway. We found that curcumin remarkably ameliorated secondary brain injury after TBI, including effects on the neurological severity score and inflammation. After injection of curcumin, the neurological function score of mice decreased significantly. Curcumin exhibited antiinflammatory pharmacological effects, as reflected by inhibition of inflammatory factors (e.g., interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α). Additionally, curcumin notably reduced the expression of p-p38 according to western blotting and immunohistochemical analyses. In conclusion, curcumin remarkably alleviated posttraumatic inflammation and thus shows potential for treating inflammation associated with TBI.

Crystal face dependent wettability of α-quartz: Elucidation by time-of-flight secondary ion mass spectrometry techniques combined with molecular dynamics.

HYPOTHESIS: Quartz is one of the most common but important minerals, and its wettability plays a significant role in affecting various natural and industrial processes. Studies have revealed that different crystal faces of quartz are with different wettabilities, but its mechanism is still vague. EXPERIMENTS AND SIMULATIONS: For specifying the mechanism of crystal face dependent wettability, the contact angles of three different liquids on the crystal faces of α-quartz are measured; the time-of-flight secondary ion mass spectrometry (ToF-SIMS) is employed to establish the crystal surface models; molecular dynamics (MD) simulations with the surface models are performed to understand the wetting behavior at molecular scale. FINDINGS: Based on the contact angle measurements, the wettabilities of different crystal faces of α-quartz are found different, which can be directly attributed to the concentration of hydroxyl group on crystal faces based on ToF-SIMS results. MD simulations yield consistent results with the contact angle order recognized from experiments, revealing that the surface hydroxyl group controls the wettability of α-quartz crystal faces. It is also recognized that the pristine surface atomic arrangement, especially the surface concentration of unsaturated bond (an intrinsic property of α-quartz), is the intrinsic cause of the difference in the concentration of hydroxyl group of the crystal surface.

Forensic Application Evaluation of a Novel Canine STR System in Pembroke Welsh Corgi and Shiba Inu Groups.

AIM: To evaluate the forensic application values of 19 autosomal short tandem repeat (STR) loci in canines. METHODS: The 19 STR loci in two canine groups (Pembroke Welsh Corgis, n = 200; Shiba Inus, n = 175) were analysed by the capillary electrophoresis platform. The allele frequencies and forensic parameters were calculated, and the genetic relationships between these two canine groups and a previously reported Labrador group were analysed. RESULTS: These two canine groups conformed to the Hardy-Weinberg equilibrium at all STRs except for locus VGL3438 in the Pembroke Welsh Corgi group, and there was no linkage disequilibrium among pairwise loci at the 19 STRs. All STRs were polymorphic in the Pembroke Welsh Corgi and Shiba Inu groups, of which the locus C38 had the highest polymorphism. And it was found that the genetic relationship between the Pembroke Welsh Corgi and Labrador groups were closer in the three canine groups (Pembroke Welsh Corgi, Shiba Inu and Labrador). CONCLUSION: The 19 STR loci had high genetic polymorphisms and forensic application values in Pembroke Welsh Corgi and Shiba Inu groups.

Transcriptome research identifies four hub genes related to primary myelofibrosis: a holistic research by weighted gene co-expression network analysis.

OBJECTIVES: This study aimed to identify specific diagnostic as well as predictive targets of primary myelofibrosis (PMF). METHODS: The gene expression profiles of GSE26049 were obtained from Gene Expression Omnibus (GEO) dataset, WGCNA was constructed to identify the most related module of PMF. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Protein-Protein interaction (PPI) network were conducted to fully understand the detailed information of the interested green module. Machine learning, Principal component analysis (PCA), and expression pattern analysis including immunohistochemistry and immunofluorescence of genes and proteins were performed to validate the reliability of these hub genes. RESULTS: Green module was strongly correlated with PMF disease after WGCNA analysis. 20 genes in green module were identified as hub genes responsible for the progression of PMF. GO, KEGG revealed that these hub genes were primarily enriched in erythrocyte differentiation, transcription factor binding, hemoglobin complex, transcription factor complex and cell cycle, etc. Among them, EPB42, CALR, SLC4A1 and MPL had the most correlations with PMF. Machine learning, Principal component analysis (PCA), and expression pattern analysis proved the results in this study. CONCLUSIONS: EPB42, CALR, SLC4A1 and MPL were significantly highly expressed in PMF samples. These four genes may be considered as candidate prognostic biomarkers and potential therapeutic targets for early stage of PMF. The effects are worth expected whether in the diagnosis at early stage or as therapeutic target.

FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway.

BACKGROUND: Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target. METHODS: The ONCOMINE databases and Kaplan-Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan-Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies. RESULTS: In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway. CONCLUSION: These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.

An Immune-Related Long Non-Coding RNA Signature to Predict the Prognosis of Ewing's Sarcoma Based on a Machine Learning Iterative Lasso Regression.

The aim of this study was to construct a new immune-associated long non-coding RNA (lncRNA) signature to predict the prognosis of Ewing sarcoma (ES) and explore its molecular mechanisms. We downloaded transcriptome and clinical prognosis data from the Gene Expression Omnibus (GSE17679, which included 88 ES samples and 18 matched normal skeletal muscle samples), and used it as a training set to identify immune-related lncRNAs with different expression levels in ES. Univariable Cox regression was used to screen immune-related lncRNAs related to ES prognosis, and an immune-related lncRNA signature was constructed based on machine learning iterative lasso regression. An external verification set was used to confirm the predictive ability of the signature. Clinical feature subgroup analysis was used to explore whether the signature was an independent prognostic factor. In addition, CIBERSORT was used to explore immune cell infiltration in the high- and low-risk groups, and to analyze the correlations between the lncRNA signature and immune cell levels. Gene set enrichment and variation analyses were used to explore the possible regulatory mechanisms of the immune-related lncRNAs in ES. We also analyzed the expression of 17 common immunotherapy targets in the high- and low-risk groups to identify any that may be regulated by immune-related lncRNAs. We screened 35 immune-related lncRNAs by univariate Cox regression. Based on this, an immune-related 11-lncRNA signature was generated by machine learning iterative lasso regression. Analysis of the external validation set confirmed its high predictive ability. DPP10 antisense RNA 3 was negatively correlated with resting dendritic cell, neutrophil, and γδ T cell infiltration, and long intergenic non-protein coding RNA 1398 was positively correlated with resting dendritic cells and M2 macrophages. These lncRNAs may affect ES prognosis by regulating GSE17721_CTRL_VS_PAM3CSK4_12H_BMDC_UP, GSE2770_IL4_ACT_VS_ACT_CD4_TCELL_48H_UP, GSE29615_CTRL_VS_DAY3_ LAIV_IFLU_VACCINE_PBMC_UP, complement signaling, interleukin 2-signal transducer and activator of transcription 5 signaling, and protein secretion. The immune-related 11-lncRNA signature may also have regulatory effects on the immunotherapy targets CD40 molecule, CD70 molecule, and CD276 molecule. In conclusion, we constructed a new immune-related 11-lncRNA signature that can stratify the prognoses of patients with ES.

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients.

BACKGROUND: Osteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients. METHODS: We obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration. RESULTS: We initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells. CONCLUSION: The autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.

Screening of osteoarthritis diagnostic markers based on immune-related genes and immune infiltration.

Osteoarthritis (OA) is a chronic degenerative disease of the bone and joints. Immune-related genes and immune cell infiltration are important in OA development. We analyzed immune-related genes and immune infiltrates to identify OA diagnostic markers. The datasets GSE51588, GSE55235, GSE55457, GSE82107, and GSE114007 were downloaded from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and differentially expressed immune-related genes (DEIRGs), and functional correlation analysis was conducted. Second, CIBERSORT was used to evaluate infiltration of immune cells in OA tissue. Finally, the least absolute shrinkage and selection operator logistic regression algorithm and support vector machine-recurrent feature elimination algorithm were used to screen and verify diagnostic markers of OA. A total of 711 DEGs and 270 DEIRGs were identified in this study. Functional enrichment analysis showed that the DEGs and DEIRGs are closely related to cellular calcium ion homeostasis, ion channel complexes, chemokine signaling pathways, and JAK-STAT signaling pathways. Differential analysis of immune cell infiltration showed that M1 macrophage infiltration was increased but that mast cell and neutrophil infiltration were decreased in OA samples. The machine learning algorithm cross-identified 15 biomarkers (BTC, PSMD8, TLR3, IL7, APOD, CIITA, IFIH1, CDC42, FGF9, TNFAIP3, CX3CR1, ERAP2, SEMA3D, MPO, and plasma cells). According to pass validation, all 15 biomarkers had high diagnostic efficacy (AUC > 0.7), and the diagnostic efficiency was higher when the 15 biomarkers were fitted into one variable (AUC = 0.758). We developed 15 biomarkers for OA diagnosis. The findings provide a new understanding of the molecular mechanism of OA from the perspective of immunology.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.