Microarchitecture Alternations of Osteochondral Junction in Patients with Osteonecrosis of the Femoral Head.

The study was aimed to investigate microarchitecture of osteochondral junction in patients with osteonecrosis of the femoral head (ONFH). We hypothesis that there were microarchitecture alternations in osteochondral junction and regional differences between the necrotic region (NR) and adjacent non-necrotic region(ANR) in patients with ONFH. Femoral heads with ONFH or femoral neck fracture were included in ONFH group (n = 11) and control group (n = 11). Cylindrical specimens were drilled on the NR/ANR of femoral heads in ONFH group and matched positions in control group (CO.NR/ CO.ANR). Histology, micro-CT, and scanning electron microscope were used to investigate microarchitecture of osteochondral junction. Layered analysis of subchondral bone plate was underwent. Mankin scores on NR were higher than that on ANR or CO.NR, respectively (P < 0.001, P < 0.001). Calcified cartilage zone on the NR and ANR was thinner than that on the CO.NR and CO.ANR, respectively (P = 0.002, P = 0.002). Tidemark roughness on the NR was larger than that on the ANR (P = 0.002). Subchondral bone plate of NR and ANR was thicker than that on the CON.NR and CON.ANR, respectively (P = 0.002, P = 0.009). Bone volume fraction of subchondral bone plate on the NR was significantly decreasing compared to ANR and CON.NR, respectively (P = 0.015, P = 0.002). Subchondral bone plate on the NR had larger area percentages and more numbers of micropores than ANR and CON.NR (P = 0.002/0.002, P = 0.002/0.002). Layered analysis showed that bone mass loss and hypomineralization were mainly on the cartilage side of subchondral bone plate in ONFH. There were microarchitecture alternations of osteochondral junction in ONFH, including thinned calcified cartilage zone, thickened subchondral bone plate, decreased bone mass, altered micropores, and hypomineralization of subchondral bone plate. Regional differences in microarchitecture of osteochondral junction were found between necrotic regions and adjacent non-necrotic regions. Subchondral bone plate in ONFH had uneven distribution of bone volume fraction and bone mineral density, which might aggravate cartilage degeneration by affecting the transmission of mechanical stresses.

Pan-cancer Analysis Reveals SRC May Link Lipid Metabolism and Macrophages.

Background: SRC is a member of the membrane-associated non-receptor protein tyrosine kinase superfamily. It has been reported to mediate inflammation and cancer. However, the exact molecular mechanism involved is still not clear. Objectives: The current study was designed to explore the prognostic landscape of SRC and further investigate the relationship between SRC and immune infiltration in pan-cancer. Materials and Methods: Kaplan-Meier Plotter was used to detect the prognostic value of SRC in pan-cancer. Then using TIMER2.0 and CIBERSORT, the relationship between SRC and immune infiltration in pan-cancer was evaluated. Furthermore, the LinkedOmics database was used to screen SRC co-expressed genes, followed by functional enrichment of SRC co-expressed genes by Metascape online tool. STRING database and Cytoscape software were applied to construct and visualise the protein-protein interaction network of SRC co-expressed genes. MCODE plug-in was used to screen hub modules in the PPI network. The SRC co-expressed genes in hub modules were extracted, and the correlation analysis between interested SRC co-expressed genes and immune infiltration was conducted via TIMER2.0 and CIBERSORT. Results: Our study demonstrated that SRC expression was significantly associated with overall survival and relapse-free survival in multiple cancer types. In addition, SRC expression was significantly correlated with the immune infiltration of B cells, dendritic cells, CD4+ T cells, macrophages, and neutrophils in pan-cancer. The expression of SRC had shown to have close correlations with M1 macrophage polarisation in LIHC, TGCT, THCA, and THYM. Moreover, the genes that co-expressed with SRC in LIHC, TGCT, THCA, and THYM were mainly enriched in lipid metabolism. Besides, correlation analysis showed that SRC co-expressed genes associated with lipid metabolism were also significantly correlated with the infiltration and polarisation of macrophages. Conclusion: These results indicate that SRC can serve as a prognostic biomarker in pan-cancer and is related to macrophages infiltration and interacts with genes involved in lipid metabolism.

SMPD1 expression profile and mutation landscape help decipher genotype-phenotype association and precision diagnosis for acid sphingomyelinase deficiency.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) disorder, also known as Niemann-Pick disease (NPD) is a rare genetic disease caused by mutations in SMPD1 gene, which encodes sphingomyelin phosphodiesterase (ASM). Except for liver and spleen enlargement and lung disease, two subtypes (Type A and B) of NDP have different onset times, survival times, ASM activities, and neurological abnormalities. To comprehensively explore NPD's genotype-phenotype association and pathophysiological characteristics, we collected 144 NPD cases with strict quality control through literature mining. RESULTS: The difference in ASM activity can differentiate NPD type A from other subtypes, with the ratio of ASM activity to the reference values being lower in type A (threshold 0.045 (4.45%)). Severe variations, such as deletion and insertion, can cause complete loss of ASM function, leading to type A, whereas relatively mild missense mutations generally result in type B. Among reported mutations, the p.Arg3AlafsX76 mutation is highly prevalent in the Chinese population, and the p.R608del mutation is common in Mediterranean countries. The expression profiles of SMPD1 from GTEx and single-cell RNA sequencing data of multiple fetal tissues showed that high expressions of SMPD1 can be observed in the liver, spleen, and brain tissues of adults and hepatoblasts, hematopoietic stem cells, STC2_TLX1-positive cells, mesothelial cells of the spleen, vascular endothelial cells of the cerebellum and the cerebrum of fetuses, indicating that SMPD1 dysfunction is highly likely to have a significant effect on the function of those cell types during development and the clinicians need pay attention to these organs or tissues as well during diagnosis. In addition, we also predicted 21 new pathogenic mutations in the SMPD1 gene that potentially cause the NPD, signifying that more rare cases will be detected with those mutations in SMPD1. Finally, we also analysed the function of the NPD type A cells following the extracellular milieu. CONCLUSIONS: Our study is the first to elucidate the effects of SMPD1 mutation on cell types and at the tissue level, which provides new insights into the genotype-phenotype association and can help in the precise diagnosis of NPD.

Prognostic value of PNN in prostate cancer and its correlation with therapeutic significance.

Prostate cancer (PCa) is the most common malignancy. New biomarkers are in demand to facilitate the management. The role of the pinin protein (encoded by PNN gene) in PCa has not been thoroughly explored yet. Using The Cancer Genome Atlas (TCGA-PCa) dataset validated with Gene Expression Omnibus (GEO) and protein expression data retrieved from the Human Protein Atlas, the prognostic and diagnostic values of PNN were studied. Highly co-expressed genes with PNN (HCEG) were constructed for pathway enrichment analysis and drug prediction. A prognostic signature based on methylation status using HCEG was constructed. Gene set enrichment analysis (GSEA) and the TISIDB database were utilised to analyse the associations between PNN and tumour-infiltrating immune cells. The upregulated PNN expression in PCa at both transcription and protein levels suggests its potential as an independent prognostic factor of PCa. Analyses of the PNN's co-expression network indicated that PNN plays a role in RNA splicing and spliceosomes. The prognostic methylation signature demonstrated good performance for progression-free survival. Finally, our results showed that the PNN gene was involved in splicing-related pathways in PCa and identified as a potential biomarker for PCa.

Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer.

The immune microenvironment is a culmination of the collaborative effort of immune cells and is important in cancer development. The underlying mechanisms of the tumor immune microenvironment in regulating prostate cancer (PRAD) are unclear. In the current study, 144 natural killer cell-related genes were identified using differential expression, single-sample gene set enrichment analysis, and weighted gene coexpression network analysis. Furthermore, VCL, ACTA2, MYL9, MYLK, MYH11, TPM1, ACTG2, TAGLN, and FLNC were selected as hub genes via the protein-protein interaction network. Based on the expression patterns of the hub genes, endothelial, epithelial, and tissue stem cells were identified as key cell subpopulations, which could regulate PRAD via immune response, extracellular signaling, and protein formation. Moreover, 27 genes were identified as prognostic signatures and used to construct the risk score model. Receiver operating characteristic curves revealed the good performance of the risk score model in both the training and testing datasets. Different chemotherapeutic responses were observed between the low- and high-risk groups. Additionally, a nomogram based on the risk score and other clinical features was established to predict the 1-, 3-, and 5-year progression-free interval of patients with PRAD. This study provides novel insights into the molecular mechanisms of the immune microenvironment and its role in the pathogenesis of PARD. The identification of key cell subpopulations has a potential therapeutic and prognostic use in PRAD.

An intron SNP rs2069837 in IL-6 is associated with osteonecrosis of the femoral head development.

BACKGROUND: Genetic polymorphisms play a crucial role in the development of osteonecrosis of the femoral head (ONFH). This study mainly explored the association of IL-6 variants and ONFH susceptibility among the Chinese Han population. METHODS: Two variants (rs2069837, and rs13306435) in the IL-6 gene were identified and genotyped from 566 patients with ONFH and 566 healthy controls. The associations between IL-6 polymorphisms and ONFH susceptibility were assessed using odds ratio (OR) and 95% confidence interval (95% CI) via logistic regression. The potential function of these two variants was predicted by the HaploReg online database. RESULTS: The results of the overall analysis revealed that IL-6 rs2069837 was correlated with decreased risk of ONFH among the Chinese Han population (p < 0.05). In stratified analysis, rs2069837 also reduced the susceptibility to ONFH in older people (> 51 years), males, nonsmokers, and nondrinkers (p < 0.05). However, no associations between rs13306435 and ONFH susceptibility were observed (p > 0.05). CONCLUSIONS: To sum up, we suggested that rs2069837 G>A polymorphism in the IL-6 gene was significantly associated with a decreased risk of ONFH among the Chinese Hans. These findings underscored the crucial role of IL-6 rs2069837 in the occurrence of ONFH.

Elucidating the Mechanism of Condensation-Mediated Degradation of Organofunctional Silane Self-Assembled Monolayer Coatings.

Dropwise condensation is favorable for numerous industrial and heat/mass transfer applications due to the enhanced heat transfer performance that results from efficient condensate removal. Organofunctional silane self-assembled monolayer (SAM) coatings are one of the most common ultrathin low surface energy materials used to promote dropwise condensation of water vapors because of their minimal thermal resistance and scalable synthesis process. These SAM coatings typically degrade (i.e., condensation transitions from the efficient dropwise mode to the inefficient filmwise mode) rapidly during water vapor condensation. More importantly, the condensation-mediated coating degradation/failure mechanism(s) remain unknown and/or unproven. In this work, we develop a mechanistic understanding of water vapor condensation-mediated organofunctional silane SAM coating degradation and validate our hypothesis through controlled coating synthesis procedures on silicon/silicon dioxide substrates. We further demonstrate that a pristine organofunctional silane SAM coating resulting from a water/moisture-free coating environment exhibits superior long-term robustness during water vapor condensation. Our molecular/nanoscale surface characterizations, pre- and post-condensation heat transfer testing, indicate that the presence of moisture in the coating environment leads to uncoated regions of the substrate that act as nucleation sites for coating degradation. By elucidating the reasons for formation of these degradation nuclei and demonstrating a method to suppress such defects, this study provides new insight into why low surface energy silane SAM coatings degrade during water vapor condensation. The proposed approach addresses a key bottleneck (i.e., coating failure) preventing the adoption of efficient dropwise condensation methods in industry, and it will facilitate enhanced phase-change heat transfer technologies in industrial applications.

Efficient Heat Shielding of Steel with Multilayer Nanocomposite Thin Film.

In an effort to protect metal substrates from extreme heat, polymer-clay multilayer thin films are studied as expendable thermal barrier coatings. Nanocomposite films with a thickness ranging from 2 to 35 µm were deposited on steel plates and exposed to the flame from a butane torch. The 35 µm coating, composed of 14 deposited bilayers of tris(hydroxymethyl)aminomethane (THAM)-buffered polyethylenimine (PEI) and vermiculite clay (VMT), decreased the maximum temperature observed on the back side of a 0.32 cm thick steel plate by over 100 °C when heated with a butane torch. Upon exposure to high temperature, the polymer and amine salt undergo pyrolysis and intumesce, subsequently forming a char and blowing gas. The char encases the nanoclay platelets, and a ceramic bubble is formed. The macro-scale bubble, in tandem with the nanocomposite coating properties, increases resistance to heat transfer into the underlying metal substrate. This heat shielding behavior occurs through radiative effects and low aggregate through-plane conductivity resulting from multilayer nanodomains and intumesced porosity (i.e., conduction through the gas as the film expands to form a ceramic bubble). These relatively thin and lightweight films could be used to protect important metal parts (in automobiles, aircraft, etc.) from fire-related damage or other types of transient high-temperature situations.

Unified Modeling Framework for Thin-Film Evaporation from Micropillar Arrays Capturing Local Interfacial Effects.

Thin-film evaporation from micropillar array porous media has gained attention in a number of fields including energy conversion and thermal management of electronics. Performance in these applications is enhanced by leveraging the geometries of the micropillar arrays to both optimize flow through these arrays via capillary pumping and increase the curved liquid-vapor interface (meniscus) area for active phase-change heat transfer. In this work, we present a unified semianalytical modeling framework to predict the dry-out heat flux accurately for thin-film evaporation from micropillar arrays with the precise prediction of (i) the pressure profile along the wick achieved by discretizing the porous media domain and (ii) the local permeability that depends on the local meniscus shape. We validate the permeability model with 3D numerical simulations and verify the accuracy of the thin-film evaporation modeling framework with available experimental data from the literature. We emphasize the importance of predicting an accurate liquid-vapor interface shape for the prediction accuracy of both the permeability and the associated governing equations for liquid propagation and phase-change heat transfer through porous materials. This modeling framework is an accurate non-CFD-based methodology for predicting the dry-out heat flux during thin-film evaporation from micropillar arrays and will serve as a general framework for modeling steady liquid-vapor phase-change processes (evaporation and condensation) in porous media.

Capillary-Enhanced Filmwise Condensation in Porous Media.

Condensation is prevalent in various industrial and heat/mass transfer applications, and improving condensation heat transfer has a direct effect on process efficiency. Enhancing condensation performance has historically been achieved via the use of low surface energy coatings to promote the efficient dropwise mode over the typical filmwise mode of condensation. However, low surface tension fluids condense on these coatings in the filmwise mode, and low surface energy coatings are generally not robust at thicknesses required to enhance condensation heat transfer. We present a robust and scalable condensation enhancement method where a high heat transfer coefficient is achieved by leveraging capillary forces within a high thermal conductivity porous wick to promote condensate removal. The capillary pressure is supported by a pump to sustain steady condensate removal, and the high thermal conductivity of the wick decreases the overall thermal resistance. This technique has the potential to enhance condensation for a variety of fluids including low surface tension fluids and is capable of operating in both a gravity and a micro- (or zero-) gravity environment. We highlight key characteristics and enhancements achieved through this capillary-enhanced filmwise condensation technique using a porous media flow model. The model results indicate that increased wick thickness and permeability increase the operational envelope and delay the failure that occurs when the condensate floods the wick. However, increasing the permeability is more favorable as both the heat transfer coefficient and the flooding threshold are increased. The working fluid thermophysical properties determine both the degree of enhancement possible and the relative contributions from gravitational and capillary pressure forces when condensation occurs in the presence of gravity. This study provides fundamental insight into an enhanced filmwise condensation technique and an improved framework for modeling porous media flows with mass addition via condensation.

Bayesian Compressive Sensing Based Optimized Node Selection Scheme in Underwater Sensor Networks.

Information acquisition in underwater sensor networks is usually limited by energy and bandwidth. Fortunately, the received signal can be represented sparsely on some basis. Therefore, a compressed sensing method can be used to collect the information by selecting a subset of the total sensor nodes. The conventional compressed sensing scheme is to select some sensor nodes randomly. The network lifetime and the correlation of sensor nodes are not considered. Therefore, it is significant to adjust the sensor node selection scheme according to these factors for the superior performance. In this paper, an optimized sensor node selection scheme is given based on Bayesian estimation theory. The advantage of Bayesian estimation is to give the closed-form expression of posterior density function and error covariance matrix. The proposed optimization problem first aims at minimizing the mean square error (MSE) of Bayesian estimation based on a given error covariance matrix. Then, the non-convex optimization problem is transformed as a convex semidefinite programming problem by relaxing the constraints. Finally, the residual energy of each sensor node is taken into account as a constraint in the optimization problem. Simulation results demonstrate that the proposed scheme has better performance than a conventional compressed sensing scheme.