Utilizing superheated steam to prepare traditional Chinese twice-cooked pork bellies, exploring its effects on the texture and flavor of fat layers.

Fat greatly impacts the overall texture and flavor of pork belly. Twice-cooked pork bellies (TPB), typically boiled and sliced before "back to pot" being stir-fried, is a classic Sichuan cuisine among stir-fried dishes. In this study, the effects of substituting conventional pan-frying (PCV) with superheated steam (SHS) technology on the sensory, texture, microstructure and flavor of the fat layers were investigated. SHS was used as an alternative to boiling (120 °C for 15, 20, 25, and 30 min), and "back to pot" stir-frying was also by SHS. TPB precooked for 25 min (P25) with SHS performed better quality characteristics than PCV, with less collagen fiber disruption and lipid droplet area, resulting in a lower hardness and higher shear force. Besides, the low-oxygen environment of SHS retarded the lipid peroxidation, showing a significantly lower MDA content than PCV. Differently, PCV exhibited more grassy and fatty flavors, while P25 exhibited a unique aroma of fruity and creamy due to its higher UFA/SFA ratios in the pre-cooking stage. Overall, the sensory scores of P25 were comparable to those of PCV (with no significant difference), revealing that SHS is expected to be applied to the industrial production of stir-fried dishes.

Corrigendum: LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

[This corrects the article DOI: 10.3389/fphys.2024.1276722.].

RBM15 activates glycolysis in M1-type macrophages to promote the progression of aortic aneurysm and dissection.

Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated in vivo through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, in vivo knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.

Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey.

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden.

Global research status of intrahepatic cholestasis of pregnancy: A bibliometric analysis of hotspots, bursts, and trends.

Background: Research on intrahepatic cholestasis of pregnancy (ICP) has recently gained attention. However, no bibliometric analysis was performed in the ICP research field. Therefore, the present study aimed to use bibliometric analysis to analyze the current research hotspots and identify global research status in ICP to reference for future research directions. Methods: We comprehensively searched the Web of Science Core Collection (WoSCC) database from its inception to December 31, 2023. Articles and reviews related to ICP were downloaded as plain text file records. We used the VOSviewer and Citespace to perform the bibliometric analysis and visualization. The main bibliometric features were tabulated and calculated. Results: A total of 1092 documents, including 921 original articles and 171 reviews, were identified in WoSCC. These publications were published in 395 journals by 4751 authors from 1250 institutions and 61 countries/regions. The global publication numbers exhibited a gradual upward trend. China, the United States, and the United Kingdom were top contributors to scientific research on ICP. King's College London, London Imperial Coll Sci Technol & Med, and Sichuan University were the most productive institutions. Catherine Williamson had published the most papers and received the most total citations. The most productive journal was Journal of Maternal-Fetal & Neonatal Medicine. The most cited paper was Beuers et al. in the Journal of Hepatology (2009). Citation burst terms showed that "risk factors" and "perinatal outcomes" were hotspots. "Inflammation", "risk factors", "perinatal outcomes", and "bile acid" have gained attention in more recent research. Conclusion: The present study comprehensively summarizes the global research status and research trends in ICP. Our study identifies hotspots, collaborative networks, and trends that will provide new insights and guidance for further research in the field.

Small-molecule organic electrode materials on carbon-coated aluminum foil for high-performance sodium-ion batteries.

Organic molecular electrode materials are promising candidates in batteries. However, direct application of small molecule materials usually suffers from drastic capacity decay and inefficient utilization of active materials because of their high solubility in organic electrolytes and low electrical conductivity. Herein, a simple strategy is found to address the above issues through coating the small-molecule organic materials on a commercialized carbon-coated aluminum foil (CCAF) as the enhanced electrode. Both the experimental and calculation results confirm that the relatively rough carbon coating on the aluminum foil not only exhibits superior adsorption capacity of small-molecule organic electrode materials with a tight contact interface but also provides continuous electronic conduction channels for the facilitated charge transfer and accelerated reaction kinetics. In addition, the carbon coating also inhibits Al corrosion in electrochemical process. As a result, by using the tetrahydroxy quinone-fused aza-phenazine (THQAP) molecule as an example, the THQAP-CCAF electrode exhibits an excellent rate performance with a high capacity of 220 and 180 mAh g-1 at 0.1 and 2 A/g, respectively, and also a remarkable cyclability with a capacity retention of 77.3% even after 1700 cycles in sodium-ion batteries. These performances are much more superior than that of batteries with the THQAP on bare aluminum foil (THQAP-AF). This work provides a substantial step in the practical application of the small-molecule organic electrode materials for future sustainable batteries.

First report of a successful surgical management of left atrial myxoma coexisting with pulmonary squamous cell carcinoma and thymic cyst.

BACKGROUND: Primary cardiac tumors, while rare, present significant clinical challenges due to their diverse pathology and presentation. Lung cancer frequently metastasizes to the heart; however, cases involving primary cardiac tumors of different origins alongside primary lung cancer are exceedingly rare in the literature. CASE PRESENTATION: We report the case of a 53-year-old female who presented with hemoptysis and was subsequently diagnosed with a left atrial myxoma, pulmonary squamous cell carcinoma, and a thymic cyst. This coexistence of multiple non-homologous tumors in a single patient is exceedingly rare. CONCLUSION: This case underscores the complexity of diagnosing and managing patients with multiple distinct tumors. The simultaneous occurrence of a primary cardiac myxoma, pulmonary squamous cell carcinoma, and thymic cyst is unprecedented, providing valuable insights for future clinical practice.

Horner syndrome immediately after deep dissection of upper thyroid pole: a case report and review of the literature.

Objectives: Horner syndrome (HS) is a rare complication of thyroid surgery. However, the relationship between the occurrence of HS and thyroid upper pole injury is still not completely clear, and there are only few reports. Case presentation: A 24-year-old female underwent endoscopic thyroidectomy for thyroid papillary carcinoma. The intraoperative examination found that the upper pole of the thyroid was bleeding. During hemostasis, the ultrasonic knife consciously peeled too deep and stopped. The patient developed HS immediately after operation. We analyzed the association between deep dissection of the upper thyroid pole and an increase in the HS incidence rate through literature searches and anatomical relationships. Conclusions: Our case report discussed the potential relationship between the degree of thyroid upper pole dissection and the occurrence of HS in routine thyroid surgery, and provided a warning for the degree of thyroid upper pole dissection in the clinic to avoid HS.

Application of modern synthetic biology technology in aromatic amino acids and derived compounds biosynthesis.

Aromatic amino acids (AAA) and derived compounds have enormous commercial value with extensive applications in the food, chemical and pharmaceutical fields. Microbial production of AAA and derived compounds is a promising prospect for its environmental friendliness and sustainability. However, low yield and production efficiency remain major challenges for realizing industrial production. With the advancement of synthetic biology, microbial production of AAA and derived compounds has been significantly facilitated. In this review, a comprehensive overview on the current progresses, challenges and corresponding solutions for AAA and derived compounds biosynthesis is provided. The most cutting-edge developments of synthetic biology technology in AAA and derived compounds biosynthesis, including CRISPR-based system, genetically encoded biosensors and synthetic genetic circuits, were highlighted. Finally, future prospects of modern strategies conducive to the biosynthesis of AAA and derived compounds are discussed. This review offers guidance on constructing microbial cell factory for aromatic compound using synthetic biology technology.

LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

Aims: Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis. Methods and materials: Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP. Results: Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90. Conclusion: Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.

Band 40/41 Surface Acoustic Wave Filters on 42°YX-Lithium Tantalate Substrate with Suppression of Transverse Leakage.

The transverse leakage of leaky surface acoustic waves (LSAWs) occurs on 42°YX-lithium tantalate substrates (42LT), which increases the insertion loss, narrows the bandwidth and flattens the roll-off of band 40/41 SAW filters and duplexers. In this work, LSAW characteristics with different metal materials and thicknesses are calculated by the finite element method (FEM), which determines the IDT material and thickness used for band 40/41 SAW filter design. To deeply understand transverse leakage and suppress it, the effects of different gap and dummy lengths on transverse leakage are simulated and discussed. Then, a new technique of using a wider dummy without any additional lithographic or depositing processes is proposed to suppress the leakage. Its effectiveness is validated by both simulations and experiments. Then, the technique is extended to applications of band 40 and 41 SAW filters. The experimental results show that with the wider dummy structure, the band 40 and 41 SAW filters achieve a more than 0.2 dB improvement in the insertion loss, a wider bandwidth and a steeper roll-off characteristic. This technique may also be extended to the other band SAW filter applications.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

ALKBH5-mediated m6A demethylation of pri-miR-199a-5p exacerbates myocardial ischemia/reperfusion injury by regulating TRAF3-mediated pyroptosis.

Myocardial ischemia‒reperfusion injury (MI/RI) is closely related to pyroptosis. alkB homolog 5 (ALKBH5) is abnormally expressed in the MI/RI models. However, the detailed molecular mechanism of ALKBH5 in MI/RI has not been elucidated. In this study, rats and H9C2 cells served as experimental subjects and received MI/R induction and H/R induction, respectively. The abundance of the targeted molecules was evaluated using RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay. The heart functions of the rats were evaluated using echocardiography, and heart injury was evaluated. Cell viability and pyroptosis were determined using cell counting Kit-8 and flow cytometry, respectively. Total m6A modification was measured using a commercial kit, and pri-miR-199a-5p m6A modification was detected by Me-RNA immunoprecipitation (RIP) assay. The interactions among the molecules were validated using RIP and luciferase experiments. ALKBH5 was abnormally highly expressed in H/R-induced H9C2 cells and MI/RI rats. ALKBH5 silencing improved injury and inhibited pyroptosis. ALKBH5 reduced pri-miR-199a-5p m6A methylation to block miR-199a-5p maturation and inhibit its expression. TNF receptor-associated Factor 3 (TRAF3) is a downstream gene of miR-199a-5p. Furthermore, in H/R-induced H9C2 cells, the miR-199a-5p inhibitor-mediated promotion of pyroptosis was reversed by ALKBH5 silencing, and the TRAF3 overexpression-mediated promotion of pyroptosis was offset by miR-199a-5p upregulation. ALKBH5 silencing inhibited pri-miR-199a-5p expression and enhanced pri-miR-199a-5p m6A modification to promote miR-199a-5p maturation and enhance its expression, thereby suppressing pyroptosis to alleviate MI/RI through decreasing TRAF3 expression.

Coexistence of pulmonary arterial hypertension and straight back syndrome in a patient with a novel BMPR2 variant affecting cytoplasmic tail domain.

BACKGROUND: Pathologic variants in the bone morphogenetic protein receptor-2 (BMPR2) gene cause a pulmonary arterial hypertension phenotype in an autosomal-dominant pattern with incomplete penetrance. Straight back syndrome is one of the causes of pseudo-heart diseases. To date, no cases of idiopathic or heritable pulmonary arterial hypertension with straight back syndrome have been reported. CASE PRESENTATION: A 30-year-old female was diagnosed with pulmonary arterial hypertension by right heart catheterization. Computed tomography revealed a decreased anteroposterior thoracic space with heart compression, indicating a straight back syndrome. Genetic analysis by whole exome sequencing identified a novel c.2423_2424delGT (p.G808Gfs*4) germline frameshift variant within BMPR2 affecting the cytoplasmic tail domain. CONCLUSIONS: This is the first report of different straight back characteristics in heritable pulmonary arterial hypertension with a novel germline BMPR2 variant. This finding may provide a new perspective on the variable penetrance of the pulmonary arterial hypertension phenotype.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets.

N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein-protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future.

The diagnostic value of GICA used for intraoperative lymph node FNA-Tg measurement to evaluate thyroid cancer metastases.

Objective: It is crucial to diagnose lymph node (LN) metastases (LNM) before or during thyroid carcinoma surgery. Measurement of thyroglobulin (Tg) in the fine needle aspirate washout (FNA-Tg) is useful to assist in the diagnosis of LNM for papillary thyroid carcinoma (PTC). This study aimed to assess the diagnostic performance of a new technique based on a colloidal gold-based immunochromatographic assay (GICA) for intraoperative FNA-Tg in diagnosing LNM. Clinical trial information: This study is registered with chictr.org.cn, ID: ChiCTR2200063561 (registered 11 September, 2022). Methods: This prospective study enrolled 51 PTC patients who underwent cervical LN dissection. A total of 150 LNs dissected from the central and lateral compartments were evaluated by FNA-Tg-GICA at three different time points and compared with frozen sections and the conventional Tg measurement method electrochemiluminescence immunoassay (ECLIA). Receiver operating characteristic curve (ROC) and area under the curve (AUC), cutoff value to discriminate benign and malignant LNs, sensitivity, specificity, and accuracy were provided. Results: The cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively. There was no significant difference between the AUCs of GICA at different time points compared to using ECLIA and frozen sections. Besides, the diagnostic performance of GICA and ECLIA showed no significant difference in evaluating LNM from central and lateral compartments or between the TgAb-positive subgroup and TgAb-negative subgroup. Conclusion: GICA is a promising method for intraoperative FNA-Tg measurement and has high value in predicting LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA.

Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies.

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease. It is characterized by pruritus, abnormal liver function and elevated total bile acid (TBA) levels, increasing the risk of maternal and fetal adverse outcomes. Its etiology remains poorly elucidated. Over the years, various omics techniques, including metabolomics, microbiome, genomics, etc., have emerged with the advancement of bioinformatics, providing a new direction for exploring the pathogenesis, diagnosis and treatment of ICP. In this review, we first summarize the role of bile acids and related components in the pathogenesis of ICP and then further illustrate the results of omics studies.

An Ultrathin Composite Polymer Electrolyte Dual-Reinforced by a Polymer of Intrinsic Microporosity (PIM-1) and Poly(tetrafluoroethylene) (PTFE) Porous Membrane.

The performances of solid-state polymer electrolytes are urgently required to be further improved for high energy density lithium metal batteries. Herein, a highly reinforced ultrathin composite polymer electrolyte (PLPP) is successfully fabricated in a large scale by densely filling the well-dispersed mixture of polyethylene oxide (PEO), Li-salt (LiTFSI) and a polymer of intrinsic microporosity (PIM-1) into porous poly(tetrafluoroethylene) (PTFE) matrix. Based on the macro-plus-micro synergistic enhancement of the PTFE with excellent mechanical properties and the soluble PIM-1 with suitable functional groups, the PLPP electrolyte exhibits excellent properties including mechanical stress, thermal stability, lithium-ion transference number, voltage window and ionic conductivity, which are all superior to the typical PEO/LiTFSI electrolytes. As a result, the Li/PLPP/Li symmetric cell can stably cycle for > 2000 h, and the LiFePO4/PLPP/Li full cell exhibits excellent rate performance (>10 C) and high cycling stability with an initial capacity of 158.8 mAh g-1 and a capacity retention of 78.8% after 300 cycles. In addition, the excellent mechanical properties as well as the wide voltage window reasonably result in the stable operation of full cells with either high-loading cathode up to 28.1 mg cm-2 or high voltage cathode with high energy density.