Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Role of TGF-ß3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-ß3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-ß3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-ß3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-ß3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-ß3 in order to evaluate its therapeutic effects. The expression pattern of TGF-ß3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-ß3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-ß3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-ß3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-ß3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

Multiomics analysis reveals that microbiota regulate fat and muscle synthesis in chickens.

Intestinal microbiota regulates the host metabolism, including fat metabolism and muscle development in mammals; however, studies on the interactions between the gut microbiome and in chickens with respect to fat metabolism and muscle development are still rare. We established a germ-free (GF) chicken model to determine the transcriptomes and metabolomes of GF and specific-pathogen-free (SPF) chickens. Transcriptome analysis showed 1,282 differentially expressed genes (DEGs) in GF and SPF chickens. The expression levels of some genes related to muscle formation were very high in SPF chickens but low in GF chickens, suggesting that GF chickens had poorer muscle development ability. In contrast, the expression levels of some fat synthesis-related genes were very low in SPF chickens but high in GF chickens, suggesting that GF chickens had a more potent fat-synthesizing ability. Metabolome analysis revealed 62 differentially expressed metabolites (DEMs) in GF and SPF chickens, of which 35 were upregulated and 27 were downregulated. Furthermore, the Pearson correlation coefficient (PCC) was calculated, and an interaction network was constructed to visualize the crosstalk between the genes, metabolites, and gut microbiota in GF and SPF chickens. The top 10 gut microbiota were positively correlated with lipid metabolism including13(S)-HpODE and 9(S)-HpOTrE, and genes related to muscle development, while were negatively correlated with genes related to fat synthesis. In conclusion, this study indicated that chicken intestinal microbiota regulate host metabolism, inhibit fat synthesis, and may promote muscle development.

Clinicopathological characteristics and prognosis of early-stage HER2 low-expression breast cancer: A single-center retrospective study.

Background: Owing to the emergence of drugs targeting human epidermal growth factor receptor 2 (HER2), remarkable prognostic enhancement has been seen for patients with HER2-positive breast carcinoma. However, anti-HER2 medicines are applicable merely to individuals with HER2-positive tumors, and the benefit for those with low HER2 expression is unclear. The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER2-expressing individuals with breast carcinoma, challenging the traditional dichotomy between HER2-negative and -positive tumors. Hence, the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER2-low expression Chinese population with early-stage breast carcinoma. Methods: Data from the database of the Breast Center of the Affiliated Hospital of Qingdao University were collected from January 2008 to December 2017. We screened a total of 4,598 patients, of which 2,837 had HER2-0 tumors and 1,761 had HER2-low tumors. Additionally, clinicopathological characteristics, survival, and prognostic information were obtained. Difference comparisons were made between HER2-0 and HER2-low groups regarding the clinical traits and outcomes. Results: We enrolled 4598 patients, with the HR-positive subjects suffering from HER2-low breast carcinoma higher in proportion than the HR-negative patients. In contrast to HER2-0 tumors, the HER2-low tumors were linked to an older median age at diagnosis, T1 tumors, N1 stage, a higher Ki-67 index, as well as inferior histological grade. Insignificant inter-group difference was noted regarding overall survival (OS), although the HER2-0 group exhibited better disease-free survival (DFS) than the HER2-low group for the entire (P = 0.003), lymph node-negative (P = 0.009) and HR-positive (P = 0.007) populations. According to the multivariate regression finding, low HER2 expression was an inferior DFS prognostic factor in the HER2-negative population with early-stage breast cancer (HR,1.33;95% CI, 1.06-1.66; P = 0.013). Conclusion: The clinical traits of the HER2-low carcinomas differed from those of HER2-0 tumors. Despite the insignificant inter-group difference in OS, the differences in DFS were found for the overall, lymph node-negative and HR-positive subjects, suggesting the possibility of HER2-low as an inferior prognostic factor for disease progression in early-stage breast cancer.

Bidirectional associations between sensorineural hearing loss and depression and anxiety: a meta-analysis.

Background: Recently, the prevalence of sensorineural hearing loss (SNL) has been increasing, and several studies have suggested that depression, anxiety, and SNL may be associated with each other, however, individual findings still have discrepancies. To the best of our knowledge, no scholars have systematically elucidated the bidirectional associations between SNL, depression, and anxiety disorders from the perspective of meta-analysis. In this study, we aimed to systematically evaluate the bidirectional associations between SHL and depressive and anxiety symptoms, and to provide evidence-based medical evidence for reducing SNL, depression, and anxiety disorders. Methods: We performed systematic review based on priori protocol that was registered with PROSPERO (No. CRD42022365963). Systematic search of PubMed, Embase, and Web of Science databases identified articles published as of June 1, 2023, on the relationship between SNL and depression and anxiety. Meta-analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CIs) for the outcome metrics, and the results were combined to assess bivariate associations between the disorders with fixed or random effects. Sensitivity and subgroup analyzes were conducted to analyze sources of heterogeneity, and Egger's and Begg's tests combined with funnel plots were applied to assess publication bias. Results: Summary analysis of the results of 20 studies covering 675,291 individuals showed that the bidirectional association between SNL and depression and anxiety disorders. The incidence (OR = 0.17, 95% CI: 0.09-0.28) and risk (OR = 1.43, 95% CI: 1.32-1.55) of depression and morbidity were higher in SNL patients than the general population. Elevated prevalence (OR = 0.46, 95% CI: 0.28-0.65) and risk (OR = 1.30, 95% CI: 1.11-1.48) of SNL were also observed in depressed patients. The prevalence of anxiety disorders among SNL patients was about 40% (OR = 0.40, 95% CI: 0.24%-0.57), which was associated with higher risk (OR = 1.83, 95% CI: 1.42-2.24) of development than the general population. Incidence of SNL in patients with anxiety disorders was approximately 31% (OR = 0.31, 95% CI: 0.29-0.33). Additionally, subgroup analyzes showed that the bidirectional associations between SNL, depression, and anxiety disorders was influenced by age, region, and mode of diagnosis of the disorders (SNL, depression, anxiety). Conclusion: There are bidirectional associations between SNL and depression and anxiety disorders, which was influenced by age and region and the method the disorders (SNL, depression, anxiety) were diagnosed.

Role of pyroptosis in diabetic cardiomyopathy: an updated review.

Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.

Levels and variations of soil bioavailable nitrogen among forests under high atmospheric nitrogen deposition.

To examine the perturbation of atmospheric nitrogen (N) deposition on soil N status and the biogeochemical cycle is meaningful for understanding forest function evolution with environmental changes. However, levels of soil bioavailable N and their environmental controls in forests receiving high atmospheric N deposition remain less investigated, which hinders evaluating the effects of enhanced anthropogenic N loading on forest N availability and N losses. This study analyzed concentrations of soil extractable N, microbial biomass N, net rates of N mineralization and nitrification, and their relationships with environmental factors among 26 temperate forests under the N deposition rates between 28.7 and 69.0 kg N ha-1 yr-1 in the Beijing-Tianjin-Hebei (BTH) region of northern China. Compared with other forests globally, forests in the BTH region showed higher levels of soil bioavailable N (NH4+, 27.1 ± 0.8 mg N kg-1; NO3-, 7.0 ± 0.8 mg N kg-1) but lower net rates of N mineralization and nitrification (0.5 ± 0.1 mg N kg-1 d-1 and 0.4 ± 0.1 mg N kg-1 d-1, respectively). Increasing N deposition levels increased soil nitrification and NO3- concentrations but did not increase microbial biomass N and N mineralization among the study forests. Soil moisture and C availability were found as dominant factors influencing microbial N mineralization and bioavailable N. In addition, by budgeting the differences in soil total N densities between the 2000s and 2010s, atmospheric N inputs to the forests were more retained in soils than lost proportionally (84% vs. 16%). We concluded that the high N deposition enriched soil N without stimulating microbial N mineralization among the study forests. These results clarified soil N status and the major controlling factors under high anthropogenic N loading, which is helpful for evaluating the fates and ecological effects of atmospheric N pollution.

Spontaneous dissection of proximal left main coronary artery in a healthy adolescent presenting with syncope: A case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a frequent cause of acute coronary syndrome in young to middle-aged women with few or no traditional cardiovascular risk factors. Chest pain is the most frequently described presenting symptom, but syncope is extremely rare. Herein, we report on a 16-year-old girl who presented with an episode of syncope occurring during a race. Despite significantly elevated troponin level, the diagnosis of the left main coronary artery SCAD with cardiogenic shock was delayed. CASE SUMMARY: A 16-year-old girl presented with an episode of syncope. Myocardial injury markers were positive. Echocardiography showed a mildly reduced left ventricular ejection fraction (50%). Although initially stable, she later experienced recurrent chest pain accompanying precordial ST segment elevation with dynamic changes and developed cardiogenic shock, necessitating emergent revascularization. Coronary angiography demonstrated almost total occlusion at the ostium and proximal segment of the left main trunk coronary artery (LMT). Intravascular ultrasound confirmed a false lumen with prominent dissection in the LMT. Percutaneous coronary intervention assisted by intra-aortic balloon pump was conducted in the LMT. A 3.5 mm × 24 mm everolimus-eluting stent was deployed to the focal lesions of the LMT. A postprocedural electrocardiogram showed alleviation of the precordial ST-segment elevation. The diagnosis of SCAD was confirmed. Transthoracic echocardiography showed an improved left ventricular ejection fraction (57%). The patient was asymptomatic during the 24-mo. follow-up period. CONCLUSION: SCAD should always be considered in the differential diagnosis of acute coronary syndrome presentations in low-risk patients, regardless of age.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Levels and variations of soil organic carbon and total nitrogen among forests in a hotspot region of high nitrogen deposition.

Human activities have distinctly enhanced the deposition levels of atmospheric nitrogen (N) pollutants into terrestrial ecosystems, but whether and to what extents soil carbon (C) and N status have been influenced by elevated N inputs remain poorly understood in the 'real' world given related knowledge has largely based on N-addition experiments. Here we reported soil organic C (OC) and total N (TN) for twenty-seven forests along a gradient of N deposition (22.4-112.9 kg N/ha/yr) in the Beijing-Tianjin-Hebei (BTH) region of northern China, a global hotspot of high N pollution. Levels of soil TN in forests of the BTH region have been elevated compared with investigations in past decades, suggesting that long-term N deposition might cause soil TN increases. Combining with major geographical and environmental factors among the study forests, we found unexpectedly that soil moisture and pH values rather than N deposition levels were major regulators of the observed spatial variations of soil OC and TN contents. As soil moisture and pH values increased with mean annual precipitation and temperature, respectively, soil C and N status in forests of the BTH region might be more responsive to climate change than to N pollution. These evidence suggests that both N deposition and climate differences should be considered into managing ecosystem functions of forest resources in regions with high N pollution.

Single-Crystal Cobalt Phosphate Nanosheets for Biomimetic Oxygen Evolution in Neutral Electrolytes.

To improve energy conversion efficiency, the development of active electrocatalysts with similar structural features to photosynthesis II systems (PS-II), which can efficiently catalyze the oxygen evolution reaction (OER), have received great research interest. Crystalline cobalt phosphate nanosheets are designed as an efficient OER catalyst in neutral media, showing outstanding performance that even outperforms the noble RuO2 benchmark. The correlation of experimental and computational results reveals that the active sites are the edge-sharing CoO9 structural motif, akin to the molecular geometry of PS-II. This unique structure can facilitate reaction intermediate adsorption and decrease the reaction energy barrier, thus improving the OER kinetics.

Designing Nanostructured Metal-Based CO2 Reduction Electrocatalysts.

Capture and conversion of CO2 into value-added chemicals and fuels is one of the most sought-after hot points at the scientific frontier. Driven by renewable energy derived electricity, the heterogeneous electrocatalyic CO2 reduction has attracted intensive interests because of the easy manipulation and high-energy-density fuels supply. Metals with general abundance and robust ability for activating CO2 have been adopted as the core-atom for developing advanced CO2 reduction electrocatalysts. As the dramatic development of nano-technology, the nanostructured metal-based materials become promising candidates for various catalytic systems. In this Review article, a general introduction and principles applied in CO2 electroreduction are summarized and discussed. Then the proposed reaction pathways of the CO2 reduction were classified and elaborated depending on the products. The state of the art advances related to the nanostructured metallic electrocatalysts are addressed as well. At last, the remaining challenges and further prospects for the construction of new nanostructured electrocatalysts for CO2 reduction and improvement of existing ones have been presented.

When Carbon Meets CO2: Functional Carbon Nanostructures for CO2 Utilization.

Major fossil fuel consumption associated with CO2 emission and socioeconomic instability has received much concern within the global community regarding the long-term sustainability and security of these commodities. The capture, sequestration, and conversion of CO2 emissions from flue gas are now becoming familiar worldwide. Nanostructured carbonaceous materials with designed functionality have been extensively used in some key CO2 exploitation processes and techniques, because of their excellent electrical conductivity, chemical/mechanical stability, adjustable chemical compositions, and abundant active sites. This review focuses on a variety of carbonaceous materials, like graphene, carbon nanotubes, amorphous porous carbons and carbon hybrid composites, which have been demonstrated promising in CO2 capture/separation and conversion (electrocatalysis and photocatalysis) to produce value-added chemicals and fuels. Along with the discussion and concerning synthesis strategies, characterization and conversion and capture/separation techniques employed, we further elaborate the structure-performance relationships in terms of elucidating active sites, reaction mechanisms and kinetics improvement. Finally, challenges and future perspectives of these carbon-based materials for CO2 applications using well-structured carbons are remarked in detail.

A lanthanide-based magnetic nanosensor as an erasable and visible platform for multi-color point-of-care detection of multiple targets and the potential application by smartphone.

The sensitive, selective and point-of-care detection of dipicolinic acid (DPA) is of great significance for the prevention of the anthrax virus and the containment of bioterrorism. In this work, a multi-color fluorescent nanoprobe composed of lanthanides and magnetic nanoparticles (Fe3O4@CePO4:Tb-EDTA-Eu) has been designed, in which the portion of Fe3O4@CePO4:Tb can be used as the internal stable signal of green fluorescence, while the EDTA-Eu part can be used as the sensitive reaction signal for monitoring DPA. Upon the addition of DPA, the red fluorescence of Eu3+ ions is significantly enhanced, while the fluorescent color of the nanoprobes can change from green to red (such as yellow-green, orange-yellow and orange-red), achieving visual multi-color fluorescent detection even by the naked eye. By using the magnetic separation method, the composites can be easily purified for point-of-care testing. More importantly, the nanoprobe fixed test pieces enable real-time analysis of DPA by using an easy-to-access color-scanning application on a smartphone. Furthermore, the fluorescence intensity can be quenched by the addition of Cu2+, which leads to a rewritable nanosensor and can be used in the detection of cysteine (Cys) with high sensitivity. With the addition of Cys, this erasable nano detection platform can also display the original multi-color visual point-of-care detection. With further optimization, this new type of multi-color fluorescent assay is promising in point-of-care clinics for multi-target diagnostics.

Titanium Phosphonate Based Metal-Organic Frameworks with Hierarchical Porosity for Enhanced Photocatalytic Hydrogen Evolution.

Photocatalytic hydrogen production is crucial for solar-to-chemical conversion process, wherein high-efficiency photocatalysts lie in the heart of this area. A photocatalyst of hierarchically mesoporous titanium phosphonate based metal-organic frameworks, featuring well-structured spheres, a periodic mesostructure, and large secondary mesoporosity, are rationally designed with the complex of polyelectrolyte and cathodic surfactant serving as the template. The well-structured hierarchical porosity and homogeneously incorporated phosphonate groups can favor the mass transfer and strong optical absorption during the photocatalytic reactions. Correspondingly, the titanium phosphonates exhibit significantly improved photocatalytic hydrogen evolution rate along with impressive stability. This work can provide more insights into designing advanced photocatalysts for energy conversion and render a tunable platform in photoelectrochemistry.

Enhanced photocatalytic activity of a B12-based catalyst co-photosensitized by TiO2 and Ru(ii) towards dechlorination.

A novel hybrid photocatalyst denoted as B12-TiO2-Ru(ii) was prepared by co-immobilizing a B12 derivative and trisbipyridine ruthenium (Ru(bpy)3 2+) on the surface of a mesoporous anatase TiO2 microspheres and was characterized by DRS, XRD, SEM and BET et al. By using the hybrid photocatalyst, DDT was completely didechlorinated and a small part of tridechlorinated product was also detected in the presence of TEOA only after 30 min of visible light irradiation. Under simulated sunlight, the hybrid exhibited a significantly enhanced photocatalytic activity for dechlorination compared with B12-TiO2 under the same condition or itself under visible light irradiation due to the additivity in the contribution of UV and visible part of the sunlight to the electron transfer. In addition, this hybrid catalyst can be easily reused without loss of catalytic efficiency. This is the first report on a B12-based photocatalyst co-sensitized by two photosensitizers with wide spectral response.

0D/2D Heterojunctions of Vanadate Quantum Dots/Graphitic Carbon Nitride Nanosheets for Enhanced Visible-Light-Driven Photocatalysis.

0D/2D heterojunctions, especially quantum dots (QDs)/nanosheets (NSs) have attracted significant attention for use of photoexcited electrons/holes due to their high charge mobility. Herein, unprecedent heterojunctions of vanadate (AgVO3 , BiVO4 , InVO4 and CuV2 O6 ) QDs/graphitic carbon nitride (g-C3 N4 ) NSs exhibiting multiple unique advances beyond traditional 0D/2D composites have been developed. The photoactive contribution, up-conversion absorption, and nitrogen coordinating sites of g-C3 N4 NSs, highly dispersed vanadate nanocrystals, as well as the strong coupling and band alignment between them lead to superior visible-light-driven photoelectrochemical (PEC) and photocatalytic performance, competing with the best reported photocatalysts. This work is expected to provide a new concept to construct multifunctional 0D/2D nanocomposites for a large variety of opto-electronic applications, not limited in photocatalysis.

Ti3C2 MXene co-catalyst on metal sulfide photo-absorbers for enhanced visible-light photocatalytic hydrogen production.

Scalable and sustainable solar hydrogen production through photocatalytic water splitting requires highly active and stable earth-abundant co-catalysts to replace expensive and rare platinum. Here we employ density functional theory calculations to direct atomic-level exploration, design and fabrication of a MXene material, Ti3C2 nanoparticles, as a highly efficient co-catalyst. Ti3C2 nanoparticles are rationally integrated with cadmium sulfide via a hydrothermal strategy to induce a super high visible-light photocatalytic hydrogen production activity of 14,342 µmol h-1 g-1 and an apparent quantum efficiency of 40.1% at 420 nm. This high performance arises from the favourable Fermi level position, electrical conductivity and hydrogen evolution capacity of Ti3C2 nanoparticles. Furthermore, Ti3C2 nanoparticles also serve as an efficient co-catalyst on ZnS or ZnxCd1-xS. This work demonstrates the potential of earth-abundant MXene family materials to construct numerous high performance and low-cost photocatalysts/photoelectrodes.

Atomically and Electronically Coupled Pt and CoO Hybrid Nanocatalysts for Enhanced Electrocatalytic Performance.

Atomically and electronically coupled Pt and CoO hybrid nanocatalysts are fabricated for electrocatalytic oxygen reduction reaction. The atomic coupling between the Pt and the CoO endows precise control of the atomic interface between the Pt and the CoO, which directly results in electron donation from the CoO to the Pt, and thus favorable tuning of the electronic structure of the Pt.

Self-Templating Synthesis of Hollow Co3 O4 Microtube Arrays for Highly Efficient Water Electrolysis.

In spite of recent advances in the synthesis of hollow micro/nanostructures, the fabrication of three-dimensional electrodes on the basis of these structures remains a major challenge. Herein, we develop an electrochemical sacrificial-template strategy to fabricate hollow Co3 O4 microtube arrays with hierarchical porosity. The resultant unique structures and integrated electrode configurations impart enhanced mass transfer and electron mobility, ensuring high activity and stability in catalyzing oxygen and hydrogen evolution reactions. Impressively, the apparent performance can rival that of state-of-the-art noble-metal and transition-metal electrocatalysts. Furthermore, this bifunctional electrode can be used for highly efficient overall water splitting, even competing with the integrated performance of Pt/C and IrO2 /C.