Exploring the NRF2-TP53 Signaling Network Through Machine Learning and Pan-Cancer Analysis: Identifying Potential targets for Cancer Prognosis Related to Oxidative Stress.

Oxidative stress (OXS) is closely related to tumor prognosis and immune response, while TP53 integrated with NRF2 is closely associated with the regulation of cancer-related OXS. Hence, constructing a TP53-NRF2 integrated OXS signature of pan-cancer is essential in predicting survival prognosis and facilitating cancer drug treatment. The pan-cancer analysis acquired the Cancer Genome Atlas (TCGA) transcriptome sequencing data from UCSC Xena, which consisted of 33 cancer types (n = 10 440). The Random Forest, Lasso regression, and Cox regression analyses are used to construct an OXS score based on 25 OXS genes. Following this, based on the OXS signature, patients are categorized into low- and high-risk groups. The disparities between the two cohorts regarding survival prognosis, immune infiltration, and drug sensitivity are delved deeply. The expression level of genes is confirmed using immunohistochemistry. The prognosis of pan-cancer patients is adequately predicted by the OXS signature with the assistance of the machine-learning algorithm. A highly accurate nomogram is developed by combining the OXS signature and clinical features. The presence of immune cells indicated that the OXS signature can be associated with the critical pathways of immunotherapy for all types of cancer, and BCL2 showed promising results. Distinct inter-group differences are observed in the OXS signature for frequently utilized antineoplastic medications in clinical settings, including first-line drugs suggested in the guidelines. In summary, by conducting a thorough analysis of OXS genes, a new model based on OXSscore is successfully developed. This model can predict the clinical prognosis and drug sensitivity of pan-cancer with high accuracy. Potential stars in the field of cancer-related anti-OXS may include drugs that target BCL2.

Analysis of CD4+ T-helper-associated hub gene signature and immune dysregulation via RNA-sequencing data in a mouse tail model of lymphedema.

Background: T-helper cells play an essential role in the progression of lymphedema. This study aimed to explore the biological significance of T-helper cell-associated genes (THAGs) in a mouse tail model of lymphedema by RNA-sequencing (RNA-seq) data. Methods: The expression profiles of a murine model of secondary lymphedema were obtained from European Nucleotide Archive (ENA) database. Differentially expressed genes (DEGs) were screened and the enrichment analysis of DEGs was conducted. THAGs were constructed by crossing the T-helper-related gene sets obtained from Molecular Signatures Database with DEGs. Protein-protein interaction (PPI) network analysis was utilized to establish T-helper-associated hub genes (THAHGs). Single-sample gene set enrichment analysis (ssGSEA) was employed to decipher differences in immune cell infiltration. The correlation between THAHGs and immune infiltration was calculated by Pearson correlation analysis. Receiver operating characteristic (ROC) curves of THAHGs were drawn to evaluate their diagnostic properties. Additionally, potential drugs and upstream transcription factors (TFs) were predicted based on THAHGs. Results: Enrichment analysis showed that lymphedematous tissue presented higher activation of biological process (BP) of T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17). The immune infiltration analysis further calculated that the relative immune abundance of follicular B cells, memory B cells, M1 macrophage, and CD4+ Tm cells was significantly elevated while the relative immune abundance of neutrophils and plasma cells were down-regulated in lymphedema. We established a list of THAHGs consisting of eight hub genes, compassing Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, Cd74. THAHGs were shown to be significantly interrelated and related to immune infiltration by Pearson correlation analysis. ROC curves showcased that the area under curve (AUC) values of THAHGs were larger than 0.70. Gata3 was the most potential TF and thalidomide might be the immunoregulatory drug for lymphedema based on THAHGs. Conclusions: Biological pathways associated with T-helpers were significantly enriched in mouse lymphedema tissue. The relative immune infiltration abundance of M1 macrophage, CD4+ Tm cells, and T-helper cells was higher in the lymphedema group. Besides, we identified the THAHGs containing eight genes, namely, Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, and Cd74. The THAHGs were closely correlated with immune infiltration results and with good diagnostic properties.

Efficacy and Safety of Surgical Procedures for Congenital Moderate and Severe Blepharoptosis: A Network Meta-analysis.

BACKGROUND: There are various surgical approaches to treat congenital moderate and severe blepharoptosis (CMSBP), but their efficacy and safety remain unclear owing to a lack of high-level evidence. This network meta-analysis aimed to evaluate the efficacy and safety of 3 classical operations: and their modifications frontal muscle flap suspension (FMS), levator palpebrae muscle shortening (LMS), conjoint fascial sheath suspension (CFSS), and modified CFSS. METHODS: We searched the PubMed, MEDLINE, Cochrane Library, CNKI, and Wanfang databases until March 2022. A Bayesian network meta-analysis was conducted for the 5 most common treatments. Outcome indicators were the number of patients with good correction and adverse events. RESULTS: Twenty-one studies were included, with 2402 eyes in 1863 patients. Five surgical methods were evaluated: FMS, LMS, CFSS, and conjoint fascial sheath suspension combined with levator muscle shortening (CFSS+LMS), or with levator palpebrae muscle composite flap suspension (CFS+L). Meta-analysis indicated that CFSS is more effective than LMS and FMS, but inferior to CFSS+LMS and CFS+L. Efficacy rates of CFSS+LMS and CFS+L were comparable. Frontal muscle flap suspension was more effective than LMS. Safety data meta-analysis found CFSS safer than FMS and LMS but with more complications than CFSS+LMS and CFS+L. Complication rates were comparable between CFS+L and CFSS+LMS, and also for FMS and LMS. CONCLUSIONS: When correcting CMSBP, CFSS+LMS, and CFS+L may be better therapeutic strategies for effectiveness and safety. Conjoint fascial sheath suspension also yielded good surgical effects. Plastic surgeons should be cautious about LMS and FMS. LEVEL OF EVIDENCE: Level IV.

The Function of T Cell Immunity in Lymphedema: A Comprehensive Review.

Lymphedema is a debilitating disease characterized by extremity edema, fibroadipose deposition, impaired lymphangiogenesis, and dysfunctional lymphatics, often with lymphatic injury secondary to the treatment of malignancies. Emerging evidence has shown that immune dysfunction regulated by T cells plays a pivotal role in development of lymphedema. Specifically, Th1, Th2, Treg, and Th17 cells have been identified as critical regulators of pathological changes in lymphedema. In this review, our aim is to provide an overview of the current understanding of the roles of CD4+ T cells, including Th1, Th2, Treg, and Th17 subsets, in the progression of lymphedema and to discuss associated therapies targeting T cell inflammation for management of lymphedema.

Effect of Si on Microstructure and Mechanical Properties of FeCrNi Medium Entropy Alloys.

FeCrNi medium entropy alloy (MEA) has been widely regarded for its excellent mechanical properties and corrosion resistance. However, insufficient strength limits its industrial application. Intermetallic particle dispersion strengthening is considered to be an effective method to improve strength, which is expected to solve this problem. In this work, microstructural evolution and mechanical behavior of FeCrNi MEA with different Si content were investigated. We found that the precipitation of fine σ particles can be formed in situ by thermomechanical treatment of Si doping FeCrNi MEAs. The FeCrNiSi0.15 MEA exhibits a good combination of strength and ductility, with yield strength and tensile elongation of 1050 MPa and 7.84%, respectively. The yield strength is almost five times that of the as-cast FeCrNi MEA. The strength enhancement is mainly attributed to the grain-boundary strengthening and precipitation strengthening caused by fine σ particles.

Preparation and Microstructure of High-Activity Spherical TaNbTiZr Refractory High-Entropy Alloy Powders.

High-activity spherical TaNbTiZr refractory high-entropy alloy (REHA) powders were successfully prepared by electrode induction melting gas atomization (EIGA) and plasma rotating electrode process (PREP) methods. Both the EIGAed and PREPed TaNbTiZr RHEA powders have a single-phase body-centered cubic (BCC) structure and low oxygen content. Compared with the EIGAed powders, the PREPed powders exhibit higher sphericity and smoother surface, but larger particle size. The average particle sizes of the EIGAed and PREPed powders are 51.8 and 65.9 µm, respectively. In addition, both the coarse EIGAed and PREPed powders have dendritic structure, and the dendrite size of the EIGAed powders is larger than that of the PREPed powders. Theoretical calculation indicates that the cooling rate of the PREPed powders is one order of magnitude higher than that of the EIGAed powders during the solidification process, and the dendritic structure has more time to grow during EIGA, which is the main reason for the coarser dendrite size of the EIGAed powders.

Cu/Fe oxide integrated on graphite felt for degradation of sulfamethoxazole in the heterogeneous electro-Fenton process under near-neutral conditions.

In the heterogeneous electro-Fenton (EF) system, high-efficiency and durable materials have attracted widespread attention as cathodes for degradation of refractory organic pollutants. In this study, a stable Cu/Fe oxide modified graphite felt electrode (Cu0.33Fe0.67NBDC-300/GF) was fabricated via a one-step hydrothermal method and subsequent thermal treatment, which used a bimetallic metal-organic framework (MOF) with 2-aminoterephthalic acid (NH2BDC) ligand as the precursor. The Cu0.33Fe0.67NBDC-300/GF electrode was used as the cathode for sulfamethoxazole (SMX) degradation in the heterogeneous EF process. The coexistence of the FeII/FeIII and CuI/CuII redox couples significantly accelerates the regeneration of FeII and promotes the generation of active free radicals (•OH and •O2-). FeIV was detected during the process, which indicates that the high-valent iron-oxo species was produced in near-neutral pH conditions. The removal efficiency of SMX (10 mg L-1) can reach 100.0% within 75 min over a wide pH range (4.0-9.0). After five cycles, the electrode retained a high stability and an outstanding catalytic capacity. Furthermore, the mechanisms and pathways for SMX degradation were proposed, the products and intermediates of SMX were analyzed, and the toxicity was evaluated. It was found that the toxicity decreased after degradation. This study displays a novel strategy for building an efficient and stable self-supporting electrode for treating antibiotic wastewater.

Microstructure and Mechanical Properties of Novel Lightweight TaNbVTi-Based Refractory High Entropy Alloys.

A series of novel lightweight TaNbVTi-based refractory high entropy alloys (RHEA) were fabricated through ball-milling and spark plasma sintering (SPS). The reinforced phase of TiO precipitates were in-situ formed due to the introduction of Al2O3 ceramic particles. The RHEA with 15% Al2O3 exhibits a high compressive yield strength (1837 MPa) and a low density (7.75 g/cm3) with an adequate ductility retention. The yield strength and density are 32% higher and 15% lower, respectively, compared to the RHEA without Al2O3 addition. The specific yield strength (237 MPa cm3/g) of the RHEAs is much higher than that of other reported RHEAs, and is mainly ascribed to the introduction of high volume fraction of Al2O3 additives, resulting in solid solution strengthening and precipitation strengthening. Meanwhile, the ductile matrix is responsible for the good compressive plasticity.

Is Pregnancy Following a TRAM or DIEP Flap Safe? A Critical Systematic Review and Meta-analysis.

BACKGROUND: Previous data were not conclusive on the safety of gestation in patients whose abdominal flaps were earlier harvested. We performed a meta-analysis to evaluate the abdominal wall complications and birth mode of pregnancy in post-TRAM or post-DIEP harvested individuals. METHODS: A literature search was performed using the PubMed, Embase, Scopus, and Google scholar database. Heterogeneity was statistically analyzed, and random effect models were applied. Publication bias was assessed by funnel plot. RESULTS: We included 25 papers that captured 56 patients giving birth to 69 healthy babies after elevation of abdominally based flaps, with a pooled abdominal complication rate of 0.00-0.09. The complication incidence in TRAM group was 0.01 (95% CI = [0.00-0.14%]) while 0.00 in the DIEP group (95% CI = [0.00-0.26%]). Discrepancies in incidence following unilaterally or bilaterally based TRAM flaps, following free or pedicled TRAM flaps, following primary sutured or mesh strengthened fascia, following MS free TRAM or conventional free TRAM could not be calculated as statistically significant. TRAM group and DIEP group patients had identical birth modes. CONCLUSIONS: The present meta-analysis did not detect evidence that abdominal walls with the prior harvest of abdominal flaps could affect the process of pregnancy or contraindicate vaginal delivery. No abdominal hernia or bulge occurred with post-DIEP pregnancies. However, such conclusions need to be substantiated by larger sample studies. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Hippocampal LASP1 ameliorates chronic stress-mediated behavioral responses in a mouse model of unpredictable chronic mild stress.

Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear. Here, using an unpredictable chronic mild stress (UCMS) paradigm, we found that the mRNA and protein levels of LASP1 were decreased in the hippocampus of stressed mice and that UCMS-induced down-regulation of LASP1 was abolished by chronic administration of fluoxetine. Adenosine-associated virus-mediated hippocampal LASP1 overexpression alleviated the UCMS-induced behavioral results of forced swimming test and sucrose preference test in stressed mice. It also restored the dendritic spine density, elevated the levels of AKT (a serine/threonine protein kinase), phosphorylated-AKT, insulin-like growth factor 2, and postsynaptic density protein 95. These findings suggest that LASP1 alleviates UCMS-provoked behavioral defects, which may be mediated by an enhanced dendritic spine density and more activated AKT-dependent LASP1 signaling, pointing to the antidepressant role of LASP1.

The Retrotransposition of L1 is Involved in the Reconsolidation of Contextual Fear Memory in Mice.

BACKGROUND: The long interspersed element-1 (L1) participates in memory formation, and DNA methylation patterns of L1 may suggest resilience or vulnerability factors for Post-Traumatic Stress Disorder (PTSD), of which the principal manifestation is a pathological exacerbation of fear memory. However, the unique roles of L1 in the reconsolidation of fear memory remain poorly understood. OBJECTIVE: The study aimed to investigate the role of L1 in the reconsolidation of context-dependent fear memory. METHODS: Mice underwent fear conditioning and fear recall in the observation chambers. Fear memory was assessed by calculating the percentage of time spent freezing in 5 min. The medial prefrontal cortex (mPFC) and hippocampus were removed for further analysis. Open Reading Frame 1 (ORF1) mRNA and ORF2 mRNA of L1 were analyzed by real-time quantitative polymerase chain reaction. After reactivation of fear memory, lamivudine was administered and its effects on fear memory reconsolidation were observed. RESULTS: ORF1 and ORF2 mRNA expressions in the mPFC and hippocampus after recent (24 h) and remote (14 days) fear memory recall exhibited augmentation via different temporal and spatial patterns. Reconsolidation of fear memory was markedly inhibited in mice treated with lamivudine, which could block L1. DNA methyltransferase mRNA expression declined following lamivudine treatment in remote fear memory recall. CONCLUSION: The retrotransposition of L1 participated in the reconsolidation of fear memory after reactivation of fear memory, and with lamivudine treatment, spontaneous recovery decreased with time after recent and remote fear memory recall, providing clues for understanding the roles of L1 in fear memory.

Microstructure and Mechanical Properties of TaNbVTiAlx Refractory High-Entropy Alloys.

A series of TaNbVTiAlx (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) refractory high-entropy alloys (RHEAs) with high specific strength and reasonable plasticity were prepared using powder metallurgy (P/M) technology. This paper studied their microstructure and compression properties. The results show that all the TaNbVTiAlx RHEAs exhibited a single BCC solid solution microstructure with no elemental segregation. The P/M TaNbVTiAlx RHEAs showed excellent room-temperature specific strength (207.11 MPa*cm3/g) and high-temperature specific strength (88.37 MPa*cm3/g at 900 °C and 16.03 MPa*cm3/g at 1200 °C), with reasonable plasticity, suggesting that these RHEAs have potential to be applied at temperatures >1200 °C. The reasons for the excellent mechanical properties of P/M TaNbVTiAl0.2 RHEA were the uniform microstructure and solid solution strengthening effect.

Copper nanoparticles selectively encapsulated in an ultrathin carbon cage loaded on SrTiO3 as stable photocatalysts for visible-light H2 evolution via water splitting.

One-nanometre-thick carbon cage encapsulated copper nanopaticles on SrTiO3 (STO) synthesized through a facile chemical vapour deposition method showed remarkable stability and performance for both photocatalytic hydrogen evolution and thermocatalytic reduction of 4-nitrophenol. X-ray photoelectron spectroscopy and Raman results demonstrate that the graphene cage effectively protected Cu nanoparticles from being oxidized.

Remarkable Visible-Light Photocatalytic Activity Enhancement over Au/p-type TiO2 Promoted by Efficient Interfacial Charge Transfer.

Metal-induced photocatalysis has emerged as a promising approach for exploiting visible-light-responsive composite materials for solar energy conversion, which is generally hindered by low photocatalytic efficiency. Herein, for the first time, an Au/p-TiO2 (p-type TiO2) strategy with the hole transfer mechanism is developed, remarkably promoting visible-light photocatalytic performance. An efficient acetone evolution rate (138 µmol·g-1·h-1) in the photocatalytic isopropyl alcohol (IPA) degradation under λex = 500 nm light (light intensity, 5.5 mW/cm2) was achieved over Au/p-TiO2, which is approximately 5 times as high as that over Au/n-TiO2 under the same conditions. Photoluminescence and electrochemical impedance spectroscopy measurements indicate enhanced charge carrier separation and transfer for Au/p-TiO2. In an elaborate study, apparent quantum efficiency and transmission electron microscopy characterization on selective PbO2 deposition over p-TiO2 revealed that visible-light-excited holes other than electrons generated in the Au interband transition transferred to p-TiO2, which is opposite to the general route in Au/n-TiO2 (n-type TiO2). Energetic holes generated in the d band of Au led to a fluent transfer across the Schottky barrier, which is further confirmed by the IPA photodegradation mechanism study with different scavengers over Au/p-TiO2. This discovery opens up new opportunities in designing and developing efficient metal semiconductor composite materials with visible-light response.

Reversible and Distance-Controllable DNA Scissor: A Regenerated Electrochemiluminescence Biosensing Platform for Ultrasensitive Detection of MicroRNA.

Reversing the switching of DNA scissors with precisely control remains a compelling goal. Herein, based on strand displacement reaction within single step, the DNA scissor realized reversible switching and further controlled the distance of end strands along the movement of DNA scissor, which has been applied for the development of a regenerated sensing platform for the ultrasensitive detection of microRNA-21 (miRNA-21) with the electrochemiluminescence (ECL) complex (PEI-Ru(II)) as luminophores and diethylenetriamine (DETA) as the coreactant. In the presence of ferrocene-labeled DNA (Fc-DNA), the DETA-labeled DNA scissor clockwise switched to "off" state based on strand displacement reaction, resulting in the significant ECL quenching of Ru(II) system. Next, by using miRNA-21 as the motive fuel, the configuration of DNA scissor could be anticlockwise switched, which significantly enhanced the ECL intensity of Ru(II) complex due to the releasing of Fc-DNA and the proximity between DETA and Ru(II) complex. The reversible switching of DNA scissor led to the remarkably enhancing of ECL signal, realizing ultrasensitive detection of miRNA-21 with an excellent detection limit of 0.17 fM, which was also applied in miRNA detection successfully from different cancer cells. Impressively, the reversible switching of DNA scissor biosensor was able to realize the regeneration of the biosensing platform by adding an additional single stranded DNA (ssDNA) based on strand displacement reaction within a single step, providing a novel concept for constructing simple and sensitive regenerated biosensor.

Fabrication of InxGa1-xN Nanowires on Tantalum Substrates by Vapor-Liquid-Solid Chemical Vapor Deposition.

InxGa1-xN nanowires (NWs) have drawn great attentions for their applications in optoelectronic and energy conversion devices. Compared to conventional substrates, metal substrates can offer InxGa1-xN NW devices with better thermal conductivity, electric conductivity, and mechanic flexibility. In this article, InxGa1-xN NWs were successfully grown on the surface of a tantalum (Ta) substrate via vapor-liquid-solid chemical vapor deposition (VLS-CVD), as characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), scanning and transmission electron microscope (STEM), and photoluminescence spectroscopy (PL). It was found that the surface pretreatment of Ta and the composition of metallic catalysts played important roles in the formation of NWs. A dimpled nitrided Ta surface combined with a catalyst of nickle is suitable for VLS-CVD growth of the NWs. The obtained InxGa1-xN NWs grew along the [1100] direction with the presence of basal stacking faults and an enriched indium composition of ~3 at.%. The successful VLS-CVD preparation of InxGa1-xN nanowires on Ta substrates could pave the way for the large-scale manufacture of optoelectronic devices in a more cost-effective way.

Microstructure and Mechanical Properties of Particulate Reinforced NbMoCrTiAl High Entropy Based Composite.

A novel metal matrix composite based on the NbMoCrTiAl high entropy alloy (HEA) was designed by the in-situ formation method. The microstructure, phase evolution, and compression mechanical properties at room temperature of the composite are investigated in detail. The results confirmed that the composite was primarily composed of body-centered cubic solid solution with a small amount of titanium carbides and alumina. With the presence of approximately 7.0 vol. % Al2O3 and 32.2 vol. % TiC reinforced particles, the compressive fracture strength of the composite (1542 MPa) was increased by approximately 50% compared with that of the as-cast NbMoCrTiAl HEA. In consideration of the superior oxidation resistance, the P/M NbMoCrTiAl high entropy alloy composite could be considered as a promising high temperature structural material.