Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease

IntroductionAlzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model.MethodsBased on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency.ResultsThe dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity.ConclusionOur study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients

Design and Synthesis of Layered Na₂Ti₃O₇ and Tunnel Na₂Ti₆O₁₃ Hybrid Structures with Enhanced Electrochemical Behavior for Sodium-Ion Batteries

A novel complementary approach for promising anode materials is proposed. Sodium titanates with layered Na2Ti3O7 and tunnel Na2Ti6O13 hybrid structure are presented, fabricated, and characterized. The hybrid sample exhibits excellent cycling stability and superior rate performance by the inhibition of layered phase transformation and synergetic effect. The structural evolution, reaction mechanism, and reaction dynamics of hybrid electrodes during the sodium insertion/desertion process are carefully investigated. In situ synchrotron X‐ray powder diffraction (SXRD) characterization is performed and the result indicates that Na+ inserts into tunnel structure with occurring solid solution reaction and intercalates into Na2Ti3O7 structure with appearing a phase transition in a low voltage. The reaction dynamics reveals that sodium ion diffusion of tunnel Na2Ti6O13 is faster than that of layered Na2Ti3O7. The synergetic complementary properties are significantly conductive to enhance electrochemical behavior of hybrid structure. This study provides a promising candidate anode for advanced sodium ion batteries (SIBs)

A Study on the Aesthetic Preference of Bamboo Weaving Patterns Based on Eye Movement Experiments

Bamboo weaving is an intangible cultural heritage in China. Exploring people’s aesthetic preferences for bamboo weaving patterns to better serve the design of bamboo architectural decoration can help promote the upgrading of traditional crafts. This study explored the differences between genders in the oculomotor indicators in different bamboo weaving patterns through an eye-movement experimental study combined with a subjective questionnaire to explore whether different genders have aesthetic preferences for people’s pictures of bamboo weaving patterns. The results showed that both males and females preferred less visually striking and softer corrugated patterns, with males paying more attention to the more ‘angular’ hexagonal and triangular patterns, while females were more interested in the more regular and uniform brickwork and diagonal patterns

A novel high voltage battery cathodes of Fe\u3csup\u3e2+\u3c/sup\u3e/Fe\u3csup\u3e3+\u3c/sup\u3esodium fluoro sulfate lined with carbon nanotubes for stable sodium batteries

Current trends in battery research are promoting the development of feasible methods to prepare electrode materials with new architectures that can meet the requirements of high energy density associated with sodium ion batteries (SIB). It is logical to use solid-state processing techniques to fabricate SIB electrode materials due to its ease of handling and capability for large-scale production. From the SIB standpoint, the sulfate based polyanionic system is well known for its high operating voltage. The present study utilizes a hitherto-unknown solid-state process with an entirely new composition to develop an electrode comprising earth abundant carbon, sodium, sulfur, fluorine, and iron materials. This new NaFeSO4F-CNT system, where CNT is carbon nanotube, obtained by the solid-state technique, exhibits a highly stable Fe2+/Fe3+redox couple and achieves a capacity of ∼110 mAg−1at 0.1C with capacity retention of \u3e91% after 200 cycles (1C). This is the best-ever reversible, high potential sulfate based cathode for sodium ion batteries reported to date. This study also provides an in-depth understanding of the outstanding electrochemical performance of this novel electrode. These findings can make it possible to achieve maximum performance from potential electrodes, when the operating temperature is limited to 350 °C or below

Porous hexagonal boron nitride sheets: effect of hydroxyl and secondary amino groups on photocatalytic hydrogen evolution

Hexagonal boron nitride (<i>h</i>-BN), an emerging two-dimensional material, has attracted great attention in various fields. However, due to its large band gap (ca. 6 eV), <i>h</i>-BN has not yet been exploited as a photocatalyst. Here, we demonstrate a porous <i>h</i>-BN sheets with rich hydroxyl (-OH) and secondary amino (-NH) groups, which can effectively decrease the band gap of <i>h</i>-BN. Porous <i>h</i>-BN sheets were synthesized via combustion of boron acid and urea at high temperature under nitrogen atmosphere. The as-obtained porous <i>h</i>-BN has a narrower band gap and a higher photocatalytic activity on hydrogen evolution than commercial <i>h</i>-BN. To further understand this photocatalytic performance, we investigated the groups, structure, and related optical and electrochemical properties for both porous and commercial <i>h</i>-BN. This work holds promise for <i>h</i>-BN to be used in the photocatalysis field

Three-Dimensional Chestnut-Like Architecture Assembled from NaTi3O6(OH)·2H2O@N-Doped Carbon Nanosheets with Enhanced Sodium Storage Properties

The application of sodium titanate anodes of low cost, feasible operating voltage, and nontoxic nature were severely hindered by their inferior cycling stability and poor rate capability. Here, three-dimensional (3D) chestnut-like NaTi3O6(OH)·2H2O@N-doped carbon nanospheres (NTOH@CN) with loose crystal structures were prepared by a self-sacrificed template method. The nanospheres were composed of nanosheets and linked with nanowires, which interweaved to construct a meshwork structure. The growth mechanism of unique 3D NTOH@CN nanospheres was investigated by tracking the synthesis process of different hydrothermal durations. The rate performances of 3D NTOH@CN were superior to that of NaTi3O6(OH)·2H2O irregular spheres assembled from nanosheets (3D NTOH) and NaTi3O6(OH)·2H2O nanosheets (two-dimensional NTOH). Excellent cycling and rate performance were obtained due to their open crystal structure, unique 3D nanosphere morphology with short diffusion paths, N-doped carbon surrounding, and the solid solution reaction. In addition, the reaction mechanism, morphology change, and dynamics research during the sodium insertion/desertion process have been carefully studied. Based on varying ex situ analyses, the irreversible metallic titanium formation and the excellent structural stability of nanosphere morphology have been evidenced. The pseudocapacitive phenomenon was also detected, which effectively enhanced Na+ ion storage capability. The systematical and comprehensive study provide a holograph for the design and synthesis of sodium titanate nanostructures

Effect of the Binder during Ultra-Precision Polishing of Tungsten Carbide Using a Semirigid Bonnet Tool

Tungsten carbide (WC) has the characteristics of high hardness, high strength, corrosion resistance, wear resistance and excellent fracture toughness. Accordingly, it has been commonly used as the material for cutting tools and molds in glass-forming techniques. To obtain ultra-smooth surfaces, fine polishing of WC is indispensable. However, the efficiency of WC polishing is low using the existing polishing methods, and the mechanism behind the polishing process requires further investigation. Specifically, the effect of the binder in WC polishing is not clear since there are different kinds of WC with various weight percentages of the binder. In this paper, we present the findings of a study on the polishing performance of two kinds of WC material, with and without the binder, using a semi-rigid (SR) bonnet polishing tool. A series of experiments were performed on a 6-DOF robotic polishing instrument to investigate the material-removal characteristics, surface integrity and sub-surface damage after polishing. The results demonstrate that the SR bonnet polishing tool successfully reduced the surface roughness of WC with and without the binder to the nanometric level, though the lowest surface roughness was obtained on binder-less WC. No obvious sub-surface damage was observed under SEM inspection, while the processing efficiency was greatly improved owing to the high material removal rate of the tool. Based on our analysis of key polishing parameters and corresponding surface integrities, the effect of the binder on the polishing performance is explained, which offers excellent guidance for WC polishing

Interpreting Abnormal Charge−Discharge Plateau Migration in CuxS during Long-Term Cycling

Voltage polarization during cycling, the charge potential increase of anode or discharge plateau decrease of cathode, is widely observed and would lower the output voltage. Conversely, an anomalous potential plateau negative migration phenomenon was observed in CuxS anode of sodium-ion battery. In this study, the background mechanism was clarified from the switch of intercalation-conversion reactions and structure evolution. The dynamic cooperation between intercalation and conversion reactions may root the potential plateau negative migration during cycling. In the initial stage, the intercalation-type reaction with Na3Cu4S4 and Na4Cu2S3 products at 2.13 and 1.92 V would dominate the early migration process of potential plateaus. In the second stage, the conversion-type reaction dominated by Na2S and metallic copper formed at 1.85 and 1.53 V in the later period. The aforementioned results would provide new perspective on the electrochemical behavior of transition-metal sulfide anode and provide a clue for reducing voltage polarization

Abstract 1138: The emerging role of thioredoxin-1 on ROS and metabolic reprogramming in cisplatin resistant lung cancer

Abstract Cisplatin resistance remains a major problem in treating lung cancer. We have discovered that all cisplatin resistant (CR) cells, regardless of their signaling mechanism, possess decreased levels of thioredoxin-1 (TRX1) in vitro and in vivo resulting in higher basal levels of ROS (Reactive Oxygen Species) accumulation. Although decreased TRX1 contributes to higher ROS levels in CR cells, we have found that these CR cells also possess elevate number and active mitochondria as evidence by increased oxygen consumption (4x higher than parental cells) and more intense mitochondria specific fluorescence (mitoTracker) as well as significantly higher mitochondrial membrane potential. These factors could also contribute to higher ROS production. Higher mitochondria activity and ROS also suggest that CR cells may rely more on oxidative metabolism (OXMET). We validated the involvement of specific OXMET components as well as the impact of TRX1 on CR cell metabolism. We examined key proteins in the TCA cycle in SCLC1 (parental), SR2 (resistance counterpart), and TRX1 over-expressing SR2 cells (SR2TRX+). We found that citrate synthetase, the first rate determining enzyme in the TCA cycle, is not changed but ATP-citrate lyase levels exhibit a 3fold increase. Fumarase (FH) which participates in the maintenance of succinate and fumarate equilibrium is increased in SR2 (1.8fold), but attenuates in TRX1 transfected cells, SR2TRX+. This finding implies that SR2 produces more fumarate, a known by-product from urea cycle. We then evaluated argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL), the two key enzymes in urea cycle which generate arginine. While ASL shows no changes, ASS mRNA is 30fold higher in SR2 compares to SCLC1. These results indicate that SCLC1 require an exogenous arginine supply for their growth while SR2 do not. Indeed, we found that SCLC1 could not withstand arginine free media supplement with citrulline (only 30% of cells survive after 48h). In contrast, SR2 which expressed ASS can survive in arginine free media with 80% of cells still viable at 48h. Importantly, over-expression of TRX1 suppresses ASS in SR2 which in turn sensitizes them to arginine deprivation. It is also known that HIF1α negatively regulates ASS and TRX1 is known to increase HIF1α. Thus lower TRX1 found in CR cells most likely increase ASS via decreased HIF1α expression. Here, we found that HIF1α is less in SR2 which may also contribute to decreased glycolysis. To consider this possibility, we assay lactate production and found lower amount of lactic acid in media from CR cells (0.013 vs. 0.009 nM/well/cell, SCLC1 vs. SR2; p=&amp;lt;0.05). Overall, our findings suggest that alteration in tumor metabolism in CR cells is most likely mediated by TRX1 through ROS. These findings may have future clinical application in treating CR patients using agents which generate ROS or target mitochondria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1138. doi:1538-7445.AM2012-1138</jats:p