Molecular and Functional Profiling of Gαi as an Intracellular pH Sensor.

Heterotrimeric G proteins (Gα, Gß and Gγ) act downstream of G-protein-coupled receptors (GPCRs) to mediate signaling pathways that regulate various physiological processes and human disease conditions. Previously, human Gαi and its yeast homolog Gpa1 have been reported to function as intracellular pH sensors, yet the pH sensing capabilities of Gαi and the underlying mechanism remain to be established. Herein, we identify a pH sensing network within Gαi, and evaluate the consequences of pH modulation on the structure and stability of the G-protein. We find that changes over the physiological pH range significantly alter the structure and stability of Gαi-GDP, with the protein undergoing a disorder-to-order transition as the pH is raised from 6.8 to 7.5. Further, we find that modulation of intracellular pH in HEK293 cells regulates Gαi-Gßγ release. Identification of key residues in the pH-sensing network allowed the generation of low pH mimetics that attenuate Gαi-Gßγ release. Our findings, taken together, indicate that pH-dependent structural changes in Gαi alter the agonist-mediated Gßγ dissociation necessary for proper signaling.

The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity.

Cardiovascular disease is the main factor contributing to the global burden of diseases, and the cardiotoxicity caused by anticancer drugs is an essential component that cannot be ignored. With the development of anticancer drugs, the survival period of cancer patients is prolonged; however, the cardiotoxicity caused by anticancer drugs is becoming increasingly prominent. Currently, cardiovascular disease has emerged as the second leading cause of mortality among long-term cancer survivors. Anticancer drug-induced cardiotoxicity has become a frontier and hot topic. The discovery of epigenetics has given the possibility of environmental changes in gene expression, protein synthesis, and traits. It has been found that epigenetics plays a pivotal role in promoting cardiovascular diseases, such as heart failure, coronary heart disease, and hypertension. In recent years, increasing studies have underscored the crucial roles played by epigenetics in anticancer drug-induced cardiotoxicity. Here, we provide a comprehensive overview of the role and mechanisms of epigenetics in anticancer drug-induced cardiotoxicity.Author details: Kindly check and confirm whether the corresponding author affiliation is correctly identified.We have checked the corresponding author affiliation is correct.

Profiling population-wide exposure to environmental chemicals: A case study of naphthalene.

Long-term exposure to environmental chemicals can detrimentally impact human health, and understanding the relationship between age distribution and levels of external and internal exposure is crucial. Nonetheless, existing methods for assessing population-wide exposure across age groups are limited. To bridge this research gap, we introduced a modeling approach designed to assess both chronic external and internal exposure to chemicals at the population level. The external and internal exposure assessments were quantified in terms of the average daily dose (ADD) and steady-state blood concentration of the environmental chemical, respectively, which were categorized by age and gender groups. The modeling process was presented within a spreadsheet framework, affording users the capability to execute population-wide exposure analyses across a spectrum of chemicals. Our simulation outcomes underscored a salient trend: younger age groups, particularly infants and children, exhibited markedly higher ADD values and blood concentrations of environmental chemicals compared to their older counterparts. This observation is due to the elevated basal metabolic rate per unit of body weight characteristic of younger individuals, coupled with their diminished biotransformation kinetics of xenobiotics within their livers. These factors collectively contribute to increased intake rates of environmental chemicals per unit of body weight through air and food consumption, along with heightened bioaccumulation of these chemicals within their bodies (e.g., blood). Furthermore, we augmented the precision of the external and internal exposure assessment by incorporating the age distribution across the population. The simulation outcomes unveiled that, to estimate the central tendency of the population's exposure levels, employing the baseline value group (age group 21-30) or the surrogate age of 25 serves as a simple yet dependable approach. However, for comprehensive population protection, our recommendation aligns with conducting exposure assessments for the younger age groups (age group 0-11). Future studies should integrate individual-level exposure assessment, analyze vulnerable population groups, and refine population structures within our developed model.

Predicting PFAS fate in fish: Assessing the roles of dietary, respiratory, and dermal uptake in bioaccumulation modeling.

An increasing number of per- and polyfluoroalkyl substances (PFAS) exposed to the environment may pose a threat to organisms and human beings. However, there is a lack of simulations comprehensively addressing and comparing the bioaccumulation of PFAS across all three major exposure routes (oral, inhalation, and dermal), especially for dermal uptake. In this study, we proposed a physiologically based kinetic (PBK) model for PFAS, aiming to predict bioaccumulation factors (BAF) in fish by considering these diverse exposure routes. 15 PFAS were used for model validation, and 11 PFAS from Taihu Lake were used for exposure contribution modeling. Approximately 64% of estimations fell within 10-fold model bias from measurements in Taihu Lake, underscoring the potential efficacy of the developed PBK model in predicting BAFs for fish. The dermal route emerges as a contributor to short-chain PFAS exposure. For example, it ranged widely from 46% to 75% (mean) for all modeling short-chain PFAS (C6-C7) in Taihu Lake. It indicated the criticality of considering dermal exposure for PFAS in fish, highlighting a gap in field studies to unravel cutaneous intake mechanisms and contributions. For longer carbon chains of PFAS (C8-C12), dermal exposure accounted for 2%-27% for all species of aquatic organisms. The fish's lipid fraction and water content played a significant role in the contribution of PFAS intake through cutaneous exposure and inhalation. Kow had a significant positive correlation with skin intake rate (p < 0.05) and gill intake rate (p < 0.001), while having a significant negative correlation with skin intake (p < 0.05) and skin intake contribution (p < 0.001). Based on the proposed modeling approach, we have introduced a simulation spreadsheet for projecting PFAS BAFs in fish tissues, hopefully broadening the predictive operational tool for a variety of chemical species.

Assessing pesticides in the atmosphere: A global study on pollution, human health effects, monitoring network and regulatory performance.

Pesticides are widely used in agriculture, but their impact on the environment and human health is a major concern. While much attention has been given to their presence in soil, water, and food, there have been few studies on airborne pesticide pollution on a global scale. This study aimed to assess the extent of atmospheric pesticide pollution in countries worldwide and identify regional differences using a scoring approach. In addition to analyzing the health risks associated with pesticide pollution, we also examined agricultural practices and current air quality standards for pesticides in these countries. The pollution scores varied significantly among the countries, particularly in Europe. Asian and Oceanic countries generally had higher scores compared to those in the Americas, suggesting a relatively higher level of air pollution caused by pesticides in these regions. It is worth noting that the current pollution levels, as assessed theoretically, pose minimal health risks to humans. However, studies in the literature have shown that excessive exposure to pesticides present in the atmosphere has been associated with various health problems, such as cancer, neuropsychiatric disorders, and other chronic diseases. Interestingly, European countries had the highest overall pesticide application intensities, but this did not necessarily correspond to higher atmospheric pesticide pollution scores. Only a few countries have established air quality standards specifically for pesticides. Furthermore, pollution scores across states in the USA were investigated and the global sampling sites were mapped. The findings revealed that the scores varied widely in the USA and the current sampling sites were limited or unevenly distributed in some countries, particularly the Nordic countries. These findings can help global relevant environmental agencies to set up comprehensive monitoring networks. Overall, the present research highlights the need to create a pesticide monitoring system and increase efforts to enhance pesticide regulation, ensure consistency in standards, and promote international cooperation.

Efficient electrochemical reduction of CO2 to CO in a flow cell device by a pristine Cu5tz6-cluster-based metal-organic framework.

The electrochemical reduction of CO2 to CO is a powerful approach to achieving carbon neutrality. Herein, we report a five-nuclear copper cluster-based metal-azolate framework CuTz-1 as an electrocatalyst for the electrochemical CO2 reduction reaction. It achieved a faradaic efficiency (FE) of 62.7% for yielding CO with a partial current density of -35.1 mA cm-2 in flow cell device, which can be preserved for more than ten hours with negligible changes of the current density and FE(CO). Studies of electrocatalytic mechanism studies revealed that the distance of Cu-N was increased, and the coordination number of the Cu ion was reduced, while the oxidation state of Cu was decreased after the electrocatalysis. These findings offer valuable insights into structural changes that influence the performance of the catalyst during the process of the electrochemical reduction of CO2 process.

RELN gene-related drug-resistant epilepsy with periventricular nodular heterotopia treated with radiofrequency thermocoagulation: a case report.

An increasing number of gene mutations associated with epilepsy have been identified, some linked to gray matter heterotopia-a common cause of drug-resistant epilepsy. Current research suggests that gene mutation-associated epilepsy should not be considered a contraindication for surgery in epilepsy patients. At present, stereoelectroencephalography-guided radiofrequency thermocoagulation is an important method to treat periventricular nodular heterotopia-associated drug-resistant epilepsy. We present a case of drug-resistant epilepsy, accompanied by periventricular nodular heterotopia and a heterozygous mutation of the RELN gene, successfully treated with radiofrequency thermocoagulation, resulting in a favorable outcome.

1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

Comparison of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules.

PURPOSE: In VATS surgery, precise preoperative localization is particularly crucial when dealing with small-diameter pulmonary nodules located deep within the lung parenchyma. The purpose of this study was to compare the efficacy and safety of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules. METHODS: This retrospective study was conducted on 164 patients who received either laser guidance or freehand hook-wire localization prior to Uni-port VATS from September 1st, 2022 to September 30th, 2023 at The First Affiliated Hospital of Soochow University. Patients were divided into laser guidance group and freehand group based on which technology was used. Preoperative localization data from all patients were compiled. The localization success and complication rates associated with the two groups were compared. The risk factors for common complications were analyzed. RESULTS: The average time of the localization duration in the laser guidance group was shorter than the freehand group (p<0.001), and the average CT scan times in the laser guidance group was less than that in the freehand group (p<0.001). The hook-wire was closer to the nodule in the laser guidance group (p<0.001). After the localization of pulmonary nodules, a CT scan showed 14 cases of minor pneumothorax (22.58%) in the laser guidance group and 21 cases (20.59%) in the freehand group, indicating no statistical difference between the two groups (p=0.763). CT scans in the laser guidance group showed pulmonary minor hemorrhage in 8 cases (12.90%) and 6 cases (5.88%) in the freehand group, indicating no statistically significant difference between the two groups (p=0.119). Three patients (4.84%) in the laser guidance group and six patients (5.88%) in the freehand group had hook-wire dislodgement, showing no statistical difference between the two groups (p=0.776). CONCLUSION: The laser guidance localization method possessed a greater precision and less localization duration and CT scan times compared to the freehand method. However, laser guidance group and freehand group do not differ in the appearance of complications such as pulmonary hemorrhage, pneumothorax and hook-wire dislodgement.

Analysis of nationwide soil pesticide pollution: Insights from China.

China is a typical agricultural country that heavily relies on pesticides. Some pesticides can remain in the soil after application and thus pose a significant threat to human health. In order to characterize the status and hazards of nationwide soil contamination, this study extracted concentration data from published literature and analyzed them by a scoring approach, standard comparison and health risk assessment. For the soil pollution score, northern regions got the highest values, such as Henan (0.63), Liaoning (0.55), Heilongjiang (0.54) and Jilin (0.53), which implies high soil pesticide residues in these provinces. In contrast, Qinghai (-0.77), Guizhou (-0.64) and Tibet (-0.63) had lower scores. China's soil pesticide standards cover only 16 pesticides, and these pesticide concentrations were all below the corresponding standards. Direct exposure to soil pesticides in this study generally posed a negligible risk to children. Furthermore, pesticide dissipation and usage intensity in each province were analyzed as they were possible influences on pollution. The result showed that soil in the northern regions could accumulate more pesticides than those in the southern regions, and this geographic pattern was basically consistent with the distribution of soil pollution. However, the relationship between agricultural activities and soil pollution was less well characterized. It is recommended to establish a long-term monitoring database for pesticides and include more pesticides in regulatory frameworks. Additionally, efforts to accelerate pesticide degradation and shift the planting structure to reduce pesticide usage can help alleviate the pressure on soil from pesticides. This study can serve as a critical reference for policymakers and stakeholders in the field of agriculture.

Comparison of Alignment Accuracy and Clinical Outcomes between a CT-Based, Saw Cutting Robotic System and a CT-Free, Jig-guided Robotic System for Total Knee Arthroplasty.

OBJECTIVE: The different cutting mode of robot-assisted TKAs may influence the accuracy of alignment. The purpose of this study was to compare alignment accuracy and early clinical outcomes between a CT-based, saw cutting robotic system (MAKO) and a CT-free, jig-guided robotic system (ROSA) for total knee arthroplasty (TKA). METHODS: A total of 20 MAKO TKAs and 20 ROSA TKAs from June 2021 to June 2022 were retrospectively analyzed. Differences in the postoperative hip-knee-ankle (HKA) angle, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), posterior tibial slope (PTS) and 3° outlier frequency of the HKA, LDFA, MPTA and PTS were studied at 3 months and 1 year of follow-up. The operative time and total blood loss (TBL) were compared between these two groups. Clinical outcomes at 1 year after surgery, including range of motion (ROM), Western Ontario McMaster University Osteoarthritis Index (WOMAC) score, and Knee Society Score-2011 (KSS-2011), were also compared between these two groups. RESULTS: The baseline characteristics of the two groups were comparable. There were no significant differences in the mean deviations of postoperative HKA, LDFA, MPTA or PTS between the two groups at 3 months or 1 year (all ps > 0.05). Moreover, there was no significant difference in the percentage of 3° outliers for HKA, LDFA, MPTA, or PTS between the two groups at 3-month or 1-year follow-up (all ps > 0.05). The mean operation time of MAKO was longer than that of ROSA (112.7 ± 12.8 min vs 94.8 ± 23.0 min, p = 0.001), but the mean TBL (1356.7 ± 648.5 mL vs 1384.5 ± 676.3 mL) and transfusion rate (15.0% vs 5.0%) were not significantly different between the two groups (all ps > 0.05). No significant differences were found in postoperative ROM, WOMAC score or KSS score at 1 year (all ps > 0.05). CONCLUSION: The MAKO and ROSA had similar accuracy and precision in TKA alignment. The clinical outcomes at 1 year after surgery were also comparable.

[Research Progress on the Prognostic Evaluation of MRD in Acute Myeloid Leukemia --Review].

Acute myeloid leukemia (AML) is a highly heterogeneous group of malignant tumors in the blood system. Although many AML patients have achieved survive for a long time through chemotherapy and targeted therapy combined with/without HSCT, but some of them still be difficult to achieve remission or early relapse after remission. Therefore, refining risk stratification and achieving individualized treatment based on prognostic indicators is of great significance. As the research on prognostic indicators of AML deepens increasingly, the prognostic stratification has been continuously improved, from the MICM typing index to the comprehensive evaluation of biological disease characteristics such as MRD. This article reviews the development of prognostic indicators for AML and the research progress of MRD on AML prognosis evaluation to better identify patients with different risks and formulate and implement accurate diagnosis and treatment programs.

Natural hyperoside extracted from hawthorn exhibits antiviral activity against porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.

Experimental studies on the characteristics of chisel picks in coal cutting for bucket wheel excavators.

Chisel pick is a basic and important rock cutting tool, and the performance of chisel pick directly affects rock mining. In this paper, a rock cutting device was developed for chisel picks cutting experiments. The influence of the depth of cutting, width of chisel pick, rake angle, back clearance angle and tip fillet radius on the cutting performance such as cutting force, normal force, and specific energy has been comprehensively studied. In addition to the general conclusions, the experimental results show that the back clearance angle has an influence range on the cutting, and the ratio of the normal force to the cutting force decreases with the increase of the rake angle; the tip fillet radius greatly improve the mean cutting force and specific energy. The experimental results will provide data support for the design of chisel picks on rock excavation machinery and a more reasonable chisel pick cutting rock mechanics model.

Phase Engineering of Nanomaterials: Transition Metal Dichalcogenides.

Crystal phase, a critical structural characteristic beyond the morphology, size, dimension, facet, etc., determines the physicochemical properties of nanomaterials. As a group of layered nanomaterials with polymorphs, transition metal dichalcogenides (TMDs) have attracted intensive research attention due to their phase-dependent properties. Therefore, great efforts have been devoted to the phase engineering of TMDs to synthesize TMDs with controlled phases, especially unconventional/metastable phases, for various applications in electronics, optoelectronics, catalysis, biomedicine, energy storage and conversion, and ferroelectrics. Considering the significant progress in the synthesis and applications of TMDs, we believe that a comprehensive review on the phase engineering of TMDs is critical to promote their fundamental studies and practical applications. This Review aims to provide a comprehensive introduction and discussion on the crystal structures, synthetic strategies, and phase-dependent properties and applications of TMDs. Finally, our perspectives on the challenges and opportunities in phase engineering of TMDs will also be discussed.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Improved muscle fatty acid composition and oxidative stability in lambs grazing on sainfoin pasture.

As a mode of animal management, grazing on pasture has the potential to improve animal performance and provide healthy meat. However, there is little information about the effects of lamb meat quality grazed on sainfoin pasture. Therefore, the present study was conducted to compare the fatty acid composition and oxidative stability of growing lambs. The twenty-four lambs were randomly divided into grazing on sainfoin pasture (GS) or feeding indoors pelleted total mixed ration (FI). The results show that GS had the higher polyunsaturated fatty acids (PUFA), especially n-3 PUFA (P = 0.002), and beneficial for nutritional index of fatty acid. Corresponding that GS had lower the Thiobarbituric acid reactive substance (TBARS) in raw (P = 0.005) and cooked meat (P = 0.008). The GS had higher total phenols (P = 0.021), ferric reducing antioxidant power (FRAP) (P = 0.048) and α-Tocopherol of meat (P = 0.004). In conclusion, grazing on sainfoin pasture in lambs can improve muscle fatty acid composition and oxidative stability than feeding indoors.

Adaptor protein HIP-55 promotes macrophage M1 polarization through promoting AP-1 complex activation.

Overwhelming macrophage M1 polarization induced by malfunction of the renin-angiotensin-aldosterone system (RAAS) initiates inflammatory responses, which play a crucial role in various cardiovascular diseases. However, the underlying regulatory mechanism remains elusive. Here, we identified adaptor protein HIP-55 as a critical regulator of macrophage M1 polarization. The expression of HIP-55 was upregulated in M1 macrophage induced by Ang II. Overexpression of HIP-55 significantly promoted Ang II-induced macrophage M1 polarization, whereas genetic deletion of HIP-55 inhibited the Ang II-induced macrophage M1 polarization. Mechanistically, HIP-55 facilitated activator protein-1 (AP-1) complex activation induced by Ang II via promoting ERK1/2 and JNK phosphorylation. Moreover, blocking AP-1 complex activation can attenuate the function of HIP-55 in macrophage polarization. Collectively, our results reveal the role of HIP-55 in macrophage polarization and provide potential therapeutic insights for cardiovascular diseases associated with RAAS dysfunction.

EV-mediated intercellular communication in acute myeloid leukemia: Transport of genetic materials in the bone marrow microenvironment.

Acute myeloid leukemia (AML) is a common hematological cancer. Cancer cells exchange information with the surrounding microenvironment, which can be transmitted by extracellular vesicles (EVs). In recent years, the genetic materials transported by EVs have attracted attention due to their important roles in different pathological processes. EV-derived ncRNAs (EV-ncRNAs) regulate physiological functions and maintain homeostasis, mainly including microRNAs, long noncoding RNAs, and circular RNAs. However, the mechanism of involvement and potential clinical application of EV-ncRNAs in AML have not been reported. Given the unique importance of the bone marrow microenvironment (BMME) for AML, a greater understanding of the communication between leukemic cells and the BMME is needed to improve the prognosis of patients and reduce the incidence of recurrence. Additionally, studies on leukemic EV-ncRNA transport guide the design of new diagnostic and therapeutic tools for AML. This review systematically describes intercellular communication in the BMME of AML and emphasizes the role of EVs. More importantly, we focus on the information transmission of EV-ncRNAs in the BMME to explore their clinical application as potential biomarkers and therapeutic targets.

2D Ruthenium-Chromium Oxide with Rich Grain Boundaries Boosts Acidic Oxygen Evolution Reaction Kinetics.

Ruthenium oxide is currently considered as the promising alternative to Ir-based catalysts employed for proton exchange membrane water electrolyzers but still faces the bottlenecks of limited durability and slow kinetics. Herein, a 2D amorphous/crystalline heterophase ac-Cr0.53 Ru0.47 O2-δ substitutional solid solution with pervasive grain boundaries (GBs) is developed to accelerate the kinetics of acidic oxygen evolution reaction (OER) and extend the long-term stability simultaneously. The ac-Cr0.53 Ru0.47 O2-δ shows a super stability with a slow degradation rate and a remarkable mass activity of 455 A gRu -1 at 1.6 V vs RHE, which is ≈3.6- and 5.9-fold higher than those of synthesized RuO2 and commercial RuO2 , respectively. The strong interaction of Cr-O-Ru local units in synergy with the specific 2D structural characteristics of ac-Cr0.53 Ru0.47 O2-δ dominates its enhanced stability. Meanwhile, high-density GBs and the shortened Ru-O bonds tailored by amorphous/crystalline structure and Cr-O-Ru interaction regulate the adsorption and desorption rates of oxygen intermediates, thus accelerating the overall acidic OER kinetics.