A new Newton method for convex optimization problems with singular Hessian matrices

In this paper, we propose a new Newton method for minimizing convex optimization problems with singular Hessian matrices including the special case that the Hessian matrix of the objective function is singular at any iteration point. The new method we proposed has some updates in the regularized parameter and the search direction. The step size of our method can be obtained by using Armijo backtracking line search. We also prove that the new method has global convergence. Some numerical experimental results show that the new method performs well for solving convex optimization problems whose Hessian matrices of the objective functions are singular everywhere

Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES

Integrated Optimization for Biofuel Management Associated with a Biomass-Penetrated Heating System under Multiple and Compound Uncertainties

The biofuel management of a biofuel-penetrated district heating system is complicated due to its association with multiple and polymorphic uncertainties. To handle uncertainties and system dynamic complexities, an inexact two-stage compound-stochastic mixed-integer programming technique is proposed, innovatively based on the integration of different uncertain optimization approaches. The proposed technique can not only address the inexact recourse problems sourced from multiple and compound uncertainties existing in the pre-regulated biofuel supply–demand match mode, but can also quantitatively analyze the conflicts between the economic target that minimizes the system cost and the risk preference that maximizes the heating service satisfaction. The developed model is applied to a real-world biofuel management case study of a district heating system to obtain the optimal biofuel management schemes subject to supply–demand, policy requirement constraints, and the financial minimization objective. The results indicate that biofuel allocation and expansion schemes are sensitive to the multiple and compound uncertainty inputs, and the corresponding biofuel-deficit change trends of three heat sources are obviously distinct with the system’s condition, varying due to the complicated interactions of the system’s components. Beyond that, a potential trade-off relationship between the heating cost and the constraint-violation risk can be obtained by observing system responses with thermalization coefficient varying

Integrated Optimization for Biofuel Management Associated with a Biomass-Penetrated Heating System under Multiple and Compound Uncertainties

The biofuel management of a biofuel-penetrated district heating system is complicated due to its association with multiple and polymorphic uncertainties. To handle uncertainties and system dynamic complexities, an inexact two-stage compound-stochastic mixed-integer programming technique is proposed, innovatively based on the integration of different uncertain optimization approaches. The proposed technique can not only address the inexact recourse problems sourced from multiple and compound uncertainties existing in the pre-regulated biofuel supply–demand match mode, but can also quantitatively analyze the conflicts between the economic target that minimizes the system cost and the risk preference that maximizes the heating service satisfaction. The developed model is applied to a real-world biofuel management case study of a district heating system to obtain the optimal biofuel management schemes subject to supply–demand, policy requirement constraints, and the financial minimization objective. The results indicate that biofuel allocation and expansion schemes are sensitive to the multiple and compound uncertainty inputs, and the corresponding biofuel-deficit change trends of three heat sources are obviously distinct with the system’s condition, varying due to the complicated interactions of the system’s components. Beyond that, a potential trade-off relationship between the heating cost and the constraint-violation risk can be obtained by observing system responses with thermalization coefficient varying

Effects of Electrospun Carbon Nanofibers’ Interlayers on High-Performance Lithium–Sulfur Batteries

Two different interlayers were introduced in lithium–sulfur batteries to improve the cycling stability with sulfur loading as high as 80% of total mass of cathode. Melamine was recommended as a nitrogen-rich (N-rich) amine component to synthesize a modified polyacrylic acid (MPAA). The electrospun MPAA was carbonized into N-rich carbon nanofibers, which were used as cathode interlayers, while carbon nanofibers from PAA without melamine was used as an anode interlayer. At the rate of 0.1 C, the initial discharge capacity with two interlayers was 983 mAh g−1, and faded down to 651 mAh g−1 after 100 cycles with the coulombic efficiency of 95.4%. At the rate of 1 C, the discharge capacity was kept to 380 mAh g−1 after 600 cycles with a coulombic efficiency of 98.8%. It apparently demonstrated that the cathode interlayer is extremely effective at shutting down the migration of polysulfide ions. The anode interlayer induced the lithium ions to form uniform lithium metal deposits confined on the fiber surface and in the bulk to strengthen the cycling stability of the lithium metal anode

Selection of bone graft type for the surgical treatment of thoracolumbar spinal tuberculosis based on the spinal instability neoplastic score: a retrospective single-center cohort study

Abstract Objectives This study aimed to establish a standard for selecting bone graft type for thoracolumbar spinal tuberculosis surgery based on the spinal instability neoplastic score (SINS). Methods Patients with thoracolumbar tuberculosis who underwent one-stage debridement posteriorly and instrumentation were divided into a structural bone graft group (SBG) (51 cases) and a non-structural bone graft group (NSBG) (54 cases) according to their SINS. SBG was performed when the SINS was ≥ 13 and NSBG was performed when it was 7 ≤ SINS ≤ 12. Baseline data, clinical outcomes, and imaging outcomes were collected and statistically analyzed between the two groups. Results Significant improvements in clinical and imaging outcomes were achieved in both groups. Compared to the SBG group, the operation time of the NSBG group was shorter, the intraoperative blood loss of the NSBG group was less, the bone fusion time of the NSBG group was faster. Conclusion Non-structural and structural bone grafting can achieve comparable therapeutic effects in patients with spinal tuberculosis, and a suitable selection of bone grafts based on quantitative SINS will make full use of the advantages of different bone grafts

A mechanism for differential sorting of the planar cell polarity proteins Frizzled6 and Vangl2 at the trans-Golgi network

In planar cell polarity (PCP), the epithelial cells are polarized along the plane of the cell surface perpendicular to the classical apical-basal axis, a process mediated by several conserved signaling receptors. Two PCP-signaling proteins, VANGL planar cell polarity protein 2 (Vangl2) and Frizzled6 (Fzd6), are located asymmetrically on opposite boundaries of the cell. Examining sorting of these two proteins at the trans-Golgi network (TGN), we demonstrated previously that the GTP-binding protein ADP-ribosylation factor-related protein 1 (Arfrp1) and the clathrin-associated adaptor protein complex 1 (AP-1) are required for Vangl2 transport from the TGN. In contrast, TGN export of Frizzled6 does not depend on Arfrp1 or AP-1. Here, to further investigate the TGN sorting process in mammalian cells, we reconstituted release of Vangl2 and Frizzled6 from the TGN into vesicles in vitro Immunoblotting of released vesicles indicated that Vangl2 and Frizzled6 exit the TGN in separate compartments. Knockdown analysis revealed that a clathrin adaptor, epsinR, regulates TGN export of Frizzled6 but not of Vangl2. Protein interaction analysis suggested that epsinR forms a stable complex with clathrin and that this complex interacts with a conserved polybasic motif in the Frizzled6 cytosolic domain to package Frizzled6 into transport vesicles. Moreover, we found that Frizzled6-epsinR binding dissociates epsinR from AP-1, which may separate these two cargo adaptors from each other to perform distinct cargo-sorting functions. Our results suggest that Vangl2 and Frizzled6 are packaged into separate vesicles that are regulated by different clathrin adaptors at the TGN, which may contribute to their asymmetric localizations

PAI-1 is a novel component of the miR-17~92 signaling that regulates pulmonary artery smooth muscle cell phenotypes

We have previously reported that miR-17~92 is critically involved in the pathogenesis of pulmonary hypertension (PH). We also identified two novel mR-17/20a direct targets PDLIM5 and PHD2 and elucidated the signaling pathways by which PDLIM5 and PHD2 regulate functions of pulmonary artery smooth muscle cells (PASMC). In addition, we have shown that plasminogen activator inhibitor-1 (PAI-1) is also downregulated in PASMC that overexpress miR-17~92. However, it is unclear whether PAI-1 is a direct target of miR-17~92 and whether it plays a role in regulating PASMC phenotype. In this study, we have identified PAI-1 as a novel target of miR-19a/b, two members of the miR-17~92 cluster. We found that the 3’-untranslated region (UTR) of PAI-1 contains a miR-19a/b binding site and that miR-19a/b can target this site to suppress PAI-1 protein expression. MiR-17/20a, two other members of miR-17~92 may also indirectly suppress PAI-1 expression through PDLIM5. PAI-1 is a negative regulator of miR-17~92-mediated PASMC proliferation. Silencing of PAI-1 induces Smad2/Calponin signaling in PASMC, suggesting that PAI-1 is a negative regulator of PASMC contractile phenotype. We also found that PAI-1 is essential for the metabolic gene expression in PASMC. Furthermore, although there is no significant change in PAI-1 levels in PASMC isolated from IPAH and APHA patients, PAI-1 is downregulated in hypoxia/Sugen-induced hypertensive rat lungs. These results suggest that miR-17~92 regulates PASMC contractile phenotype and proliferation coordinately and synergistically by direct and indirect targeting of PAI-1

MicroRNAs in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH

Data_Sheet_1_Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma.zip

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.</p