Extracellular cleavage of microglia-derived progranulin promotes diet-induced obesity.

Hypothalamic innate immune responses to dietary fats underpin the pathogenesis of obesity, in which microglia play a critical role. Progranulin (PGRN) is an evolutionarily -conserved secretory protein containing seven-and-a-half granulin (GRN) motifs. It is cleaved into GRNs by multiple proteases. In the central nervous system, PGRN is highly expressed in microglia. To investigate the role of microglia-derived PGRN in metabolism regulation, we established a mouse model with a microglia-specific deletion of the Grn gene, that encodes PGRN. Mice with microglia-specific Grn gene depletion displayed dietdependent metabolic phenotypes. Under normal diet-fed conditions, microglial Grn gene depletion produced adverse outcomes like fasting hyperglycemia and aberrant activation of hypothalamic microglia. However, when fed a high fat diet (HFD), these mice exhibited beneficial effects, including less obesity, glucose dysregulation, and hypothalamic inflammation. These differing phenotypes appear linked to increased extracellular cleavage of anti-inflammatory PGRN into proinflammatory GRNs in the hypothalamus during overnutrition. In support of this, inhibiting PGRN cleavage attenuated HFD-induced hypothalamic inflammation and obesity progression. Our results suggest that the extracellular cleavage of microglia-derived PGRN plays a significant role in promoting hypothalamic inflammation and obesity during periods of overnutrition. Therefore, therapies that inhibit PGRN cleavage may be beneficial for combating dietinduced obesity.

Impact of variant histology in the prognosis of non­muscle invasive bladder cancer with low­tumor burden: A propensity score­matched analysis with conventional urothelial carcinoma.

Bladder cancer (BCa) with variant histology (VH) is associated with an increased risk of recurrence and progression, as well as worse survival. However, the available literature does not provide the prognostic value of VH based on its tumor burden in non-muscle invasive BCa (NMIBC). The purpose of the present study was to investigate the prognosis of VH in NMIBC with low-tumor volume compared with conventional urothelial carcinoma (UC) with a similar tumor burden. The present single-center study analyzed patients diagnosed with NMIBC and retrospectively characterized them based on their VH status. Propensity scores for VH status were calculated to match patients with VH with those with conventional UC (1:3). The VH group was further divided into two subgroups based on pathological aggressiveness: Aggressive and highly aggressive variants. Oncological outcomes were compared among the three groups. Among the 494 patients with NMIBC, 60 (12.1%) had VH. Patients with VH had a higher tumor stage and grade and more multiple tumors (all P<0.05). In the matched cohort, >80% had tumors <3 cm, and >65% had solitary tumors. During a median follow-up of 42.5 months (range, 4.0-122.0 months), 35.1% (85/240) experienced recurrence and 5.4% (13/240) progressed to muscle-invasive disease. Prognosis did not differ between patients with aggressive or highly aggressive variants and those with conventional UC, including 5-year recurrence-free and pathologic progression-free survival (log-rank, P=0.510 and 0.257, respectively). Intravesical Bacillus Galmette-Guerin was the only factor associated with reduced recurrence (P<0.001). In conclusion, NMIBC with low-tumor burden and VH have similar oncologic outcomes to conventional UC with a similar tumor burden, indicating that bladder-sparing methods currently used for high-risk conventional NMIBC may be effective for managing low-tumor burden NMIBC with VH.

Prediction of the Interface Behavior of a Steel/CFRP Hybrid Part Manufactured by Stamping.

Carbon fiber-reinforced plastic (CFRP) is a lightweight material. The automotive industry has focused on producing a steel/CFRP hybrid part to reduce overall weight. After manufacturing, delamination can occur at the interface between the CFRP and steel owing to the hybrid part constituting dissimilar materials. However, most studies have focused only on designing the manufacturing processes for the hybrid part or evaluating the adhesive used at the interface. Therefore, it is necessary to predict the behavior of the interface after demolding the hybrid part. This study aimed to predict the interface behavior of a steel/CFRP hybrid part by considering its forming and cohesive properties. First, double cantilever beam (DCB) and end-notched flexure (ENF) tests were performed to obtain cohesive parameters, such as energy release rate of modes I and II (GI, GII). The experimentally obtained properties were applied to the bonding area of the hybrid part. Subsequently, a forming simulation was performed to obtain the stress of the steel blank in the hybrid part. The stress distribution after forming was utilized as the initial condition for spring-back simulation. Finally, the interface behavior of the hybrid part was predicted by a spring-back simulation. The simulation was conducted using the residual stress of steel outer and the cohesive properties on the interface, without the application of any external forces. The cases of spring-back simulation were divided as delamination occurrence and attached state. The simulation results for prediction of delamination occurrence and bonding showed good agreement in both cases with experimental ones. The proposed method would contribute to expanding the manufacturing of the hybrid part by stamping and reducing the manufacturing cost by prediction of delamination occurrence.

Characterization and Making Techniques of Calcareous Construction Materials for Phaya Thon Zu Temple in Bagan Historical Area, Myanmar.

The calcareous materials used in constructing the Phaya Thon Zu temple at the Bagan historical sites in Myanmar are mortars, plasters, and stuccos. Among them, the mortars and plasters are a mixture of original and new materials used for recent conservation treatments. In this study, the making techniques were examined through analysis of calcareous materials by production period. All calcareous materials have a mineral composition similar to soil, except calcite. Stuccos have the most refined aggregates, homogeneous particle size, and the highest lime and organic contents. They were designed to improve ease of carving and weathering resistance, considering the unique characteristics of the stuccos. Because all calcareous materials were mixed with soil, the origin of the clay materials was analyzed. It was concluded that the mortars were produced by mixing clay and sandy soil, and the original mortars showed characteristics similar to soil. It is highly possible that sandy soil from around the Htillominlo temple was used to produce new plasters, and it is estimated that a mixture of clay soil was used for the original plasters and stuccos. A clear provenance interpretation of the original and raw materials used for each construction and the mixing ratio of clay materials need to be discussed through experiments, along with the estimated provenance area of the raw calcareous materials.

Invasive strategies for rhythm control of atrial fibrillation: a narrative review.

Atrial fibrillation (AF) is the most common sustained tachyarrhythmia and its increasing prevalence has resulted in a growing healthcare burden. A recent landmark randomized trial, the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial), highlighted the importance of early rhythm control in AF, which was previously underemphasized. Rhythm control therapy includes antiarrhythmic drugs, direct-current cardioversion, and catheter ablation. Currently, catheter ablation is indicated for patients with AF who are either refractory or intolerant to antiarrhythmic drugs or who exhibit decreased left ventricular systolic function. Catheter ablation can be categorized according to the energy source used, including radiofrequency ablation (RFA), cryoablation, laser ablation, and the recently emerging pulsed field ablation (PFA). Catheter ablation techniques can also be divided into the point-by-point ablation method, which ablates the pulmonary vein (PV) antrum one point at a time, and the single-shot technique, which uses a spherical catheter to ablate the PV antrum in a single application. PFA is known to be applicable to both point-by-point and single-shot techniques and is expected to be promising owing to its tissue specificity, resulting in less collateral damage than catheter ablation involving thermal energy, such as RFA and cryoablation. In this review, we aimed to outline catheter ablation for rhythm control in AF by reviewing previous studies.

Cardiovascular outcomes in Parkinson's disease patients from a retrospective cohort study.

Parkinson's disease (PD) reports high rates of morbidity and mortality, but the risk of adverse cardiovascular outcomes in patients with PD has not been fully elucidated. This bi-center retrospective cohort study using the electronic health records (EHR) database of two tertiary hospitals screened a total of 327,292 subjects who visited the outpatient clinic, and 1194 patients with PD were propensity score-matched with a control population. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Key secondary outcomes included all-cause death, cardiovascular (CV) death, stroke, myocardial infarction (MI), heart failure hospitalization and 30-day CV death. After PS matching, MACE occurrence was not significantly different between PD and non-PD groups (18.2% vs. 17.5%, log-rank p = 0.98). Key secondary outcomes were also similar between the two groups. In patients with PD, MACE rate, and also CV risk score, were higher in patients with more severe PD (according to Hoehn and Yahr scale and unified Parkinson's disease rating scale), and after multivariable analysis, PD severity was not an independent predictor of MACE. Patients with PD are at an increased risk of adverse cardiovascular outcomes, but the contribution from other common CV risk factors cannot be ignored. The management of prevalent CV risk factors is therefore important in mitigating adverse outcomes among patients with PD.

Hyperactivation of crosslinked lipases in elastic hydroxyapatite microgel and their properties.

Effective enzyme stabilization through immobilization is essential for the functional usage of enzymatic reactions. We propose a new method for synthesizing elastic hydroxyapatite microgel (E-HAp-M) materials and immobilizing lipase using this mesoporous mineral via the ship-in-a-bottle-neck strategy. The physicochemical parameters of E-HAp-M were thoroughly studied, revealing that E-HAp-M provides efficient space for enzyme immobilization. As a model enzyme, lipase (LP) was entrapped and then cross-linked enzyme structure, preventing leaching from mesopores, resulting in highly active and stable LP/E-HAp-M composites. By comparing LP activity under different temperature and pH conditions, it was observed that the cross-linked LP exhibited improved thermal stability and pH resistance compared to the free enzyme. In addition, they demonstrated a 156% increase in catalytic activity compared with free LP in hydrolysis reactions at room temperature. The immobilized LP maintained 45% of its initial activity after 10 cycles of recycling and remained stable for over 160 days. This report presents the first demonstration of a stabilized cross-linked LP in E-HAp-M, suggesting its potential application in enzyme-catalyzed processes within biocatalysis technology.

Comparison of clinical characteristics and outcomes in hospitalized adult patients infected with respiratory syncytial virus and influenza virus.

BACKGROUND: Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. METHODS: The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. RESULTS: The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm3 vs. 7616/mm3, p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients. CONCLUSIONS: Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.

Parkinson's disease is associated with clonal hematopoiesis with TET2 mutation.

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson's disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11-2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.

Effect of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on ischemia-reperfusion injury in a rat model.

BACKGROUND: Despite advancements in reconstructive procedures, ischemia-reperfusion (I/R) injury remains a significant challenge in reconstructive surgery, with mitochondrial dysfunction playing a pivotal role. Mitochondrial transplantation has emerged as a promising therapeutic strategy to address this issue. This study aims to evaluate the impact of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on skin flap I/R models in rats. MATERIAL AND METHODS: Twenty male rats underwent I/R injury on skin flaps, with or without mitochondrial transplantation administered via intravenous or subcutaneous routes. Analysis encompassed histopathology, inflammatory, apoptotic, oxidative stress, and hypoxia markers. RESULTS: Results revealed a reduction in inflammation, apoptosis, oxidative stress, and hypoxia in the transplantation group compared to controls. CONCLUSION: The findings suggest that umbilical cord mesenchymal stem cell-derived mitochondrial transplantation shows promise in enhancing flap viability and attenuating I/R injury, offering valuable insights for improved outcomes in reconstructive surgery. However, further exploration in larger animal models and refinement of delivery methods and dosage are warranted to fully elucidate its clinical translatability.

Effects of Ulmus macrocarpa Extract and Catechin 7-O-ß-D-apiofuranoside on Muscle Loss and Muscle Atrophy in C2C12 Murine Skeletal Muscle Cells.

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-ß-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-ß-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study.

Objective: The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. Methods: This is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either "favorable" or "intermediate" risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. Results: Of the primary patterns of treatment sequences (24 sequences), "sunitinib-pazopanib" and "sunitinib-everolimus-immunotherapy" showed the most beneficial results in both OS and PFS with significantly lower hazards than "sunitinib", which is the most commonly treated agent in Korea. Considering that the "TKI-TKI" structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be "sunitinib-everolimus-immunotherapy". Conclusion: Among several sequential therapy starting with TKIs, "sunitinib-everolimus- immunotherapy" was found to be the best scheme for mRCC patients with "favorable" or "intermediate" risks.

Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

Background: There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes.

Exercise Preferences and Barriers Among Patients With Heart Failure With Reduced Ejection Fraction or Myocardial Infarction.

BACKGROUND AND OBJECTIVES: Although cardiac rehabilitation (CR) is highly recommended in patients with cardiovascular disease (CVD), participation in CR is low mainly due to access barriers. Home-based CR (HBCR) has been recommended to overcome access barriers. Exercise is a core component of CR and should be developed and implemented based on individual characteristics. We aimed to assess physical activity behaviors, exercise preferences, and exercise barriers to understand physical activity characteristics of CVD patients. METHODS: Participants were patients between the ages 19 to 75 years with a history of heart failure with reduced ejection fraction (HFrEF) or myocardial infarction (MI). They completed a cross-sectional survey at a tertiary hospital's outpatient clinic from April to June 2021. Survey data included physical activity levels, patterns, preference, and barriers of exercise. RESULTS: Participants (n=189; 143 males, 46 females, 62.1±12.0 years) were diagnosed as either HFrEF (n=160, 84.7%) or a history of MI (n=97, 51.3%). Only 26.5% of patients engaged in moderate to vigorous exercise for more than 150 minutes per week. Participants preferred exercising alone or with families. Walking (65.6%) and resistance exercises (35.4%) were favored, with outdoor (37%) and home-based (30.2%) settings preferred over fitness centers (10.6%) and hospitals (0.5%). Barriers to exercise included fatigue (34.4%), poor health perception (31.7%), and low fitness levels (30.7%). CONCLUSIONS: The results of this study can be used to develop tailored HBCR programs that consider individual preferences and address specific barriers, facilitating adequate physical activity engagement.

Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson's disease.

The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.

Risk of nosocomial coronavirus disease 2019: comparison between single- and multiple-occupancy rooms.

BACKGROUND: There is an ongoing controversy regarding whether single-occupancy rooms are superior to multiple-occupancy rooms in terms of infection prevention. We investigated whether treatment in a multiple-occupancy room is associated with an increased incidence of nosocomial coronavirus disease 2019 (COVID-19) compared with treatment in a single-occupancy room. METHODS: In this retrospective cohort study, every hospitalization period of adult patients aged ≥ 18 years at a tertiary hospital in Korea from January 1, 2022, to December 31, 2022, was analyzed. If COVID-19 was diagnosed more than 5 days after hospitalization, the case was classified as nosocomial. We estimated the association between the number of patients per room and the risk of nosocomial COVID-19 using a Cox proportional hazards regression model. RESULTS: In total, 25,143 hospitalizations per room type were analyzed. The incidence rate of nosocomial COVID-19 increased according to the number of patients per room; it ranged from 3.05 to 38.64 cases per 10,000 patient-days between single- and 6-bed rooms, respectively. Additionally, the hazard ratios of nosocomial COVID-19 showed an increasing trend according to the number of patients per room, ranging from 0.14 (95% confidence interval 0.001-1.03) to 2.66 (95% confidence interval 1.60-4.85) between single- and 6-bed rooms, respectively. CONCLUSIONS: We demonstrated that the incidence of nosocomial COVID-19 increased according to the number of patients per room. To reduce nosocomial infections by respiratory viruses, the use of multiple-occupancy rooms should be minimized.

Pulsed electrolysis for CO2 reduction: Techno-economic perspectives.

Pulsed electrolysis has emerged as a promising approach to CO2 reduction, offering a simple method to adjust product selectivity and enhance operational stability. However, conceptually applying the dynamic pulse operation process on a large scale highlights its differences when compared to conventional electrolysis processes, impacting the economic feasibility of the process. We discuss the influence of pulsed electrolysis on surface reaction mechanisms and the simulation of changes at both the continuum and smaller scales through computational modeling. Additionally, we point out considerations for applying pulsed CO2 electrolysis to a large-scale process and assess their economic implications, comparing pulsed electrolysis with constant electrolysis.