The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

A wide star-black-hole binary system from radial-velocity measurements.

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer.

BACKGROUND: Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. This study aimed to assess the safety and efficacy of cadonilimab plus anlotinib for the first-line treatment of advanced non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK/ROS1 mutations. METHODS: Patients received cadonilimab 15 mg/kg and 10 mg/kg every three weeks (Q3W) plus anlotinib at doses of 10 or 12 mg once daily for two weeks on a one-week-off schedule. The primary endpoints included safety and objective response rate (ORR). RESULTS: Sixty-nine treatment-naïve patients received cadonilimab 15 mg/kg Q3W combination (n = 49) and 10 mg/kg Q3W combination (n = 20). Treatment-related adverse events (TRAEs) were reported in 48 (98.0%) and 19 (95.0%) patients, with grade ≥3 TRAEs occurring in 29 (59.2%) and five (25.0%) patients, respectively. TRAEs leading to cadonilimab discontinuation occurred in eight (16.3%) and one (5.0%) patients in the cadonilimab 15 mg/kg Q3W and 10 mg/kg Q3W dosing groups. The confirmed ORRs were 51.0% (25/49) and 60.0% (12/20) accordingly. CONCLUSIONS: Cadonilimab 10 mg/kg Q3W plus anlotinib showed manageable safety and promising efficacy as a first-line chemo-free treatment for advanced NSCLC. GOV IDENTIFIER: NCT04646330.

In situ Activation of Molecular Oxygen at Intermetallic Spacing-Optimized Iron Network-Like Sites for Boosting Electrocatalytic Oxygen Reduction.

The oxygen reduction reaction (ORR) catalyzed by transition-metal single-atom catalysts (SACs) is promising for practical applications in energy-conversion devices, but great challenges still remain due to the sluggish kinetics of O═O cleavage. Herein, a kind of high-density iron network-like sites catalysts are constructed with optimized intermetallic distances on an amino-functionalized carbon matrix (Fe-HDNSs). Quasi-in situ soft X-ray absorption spectroscopy and in situ synchrotron infrared characterizations demonstrate that the optimized intermetallic distances in Fe-HDNSs can in situ activate the molecular oxygen by fast electron compensation through the hybridized Fe 3d‒O 2p, which efficiently facilitates the cleavage of the O═O bond to *O species and highly suppresses the side reactions for an accelerated kinetics of the 4e- ORR. As a result, the well-designed Fe-HDNSs catalysts exhibit superior performances with a half-wave potential of 0.89 V versus reversible hydrogen electrode (RHE) and a kinetic current density of 72 mA cm-2@0.80 V versus RHE, exceeding most of the noble-metal-free ORR catalysts. This work offers some new insights into the understanding of 4e- ORR kinetics and reaction pathways to boost electrochemical performances of SACs.

Fluorinated Polymer Donors for Nonfullerene Organic Solar Cells.

The rapid development of narrow-bandgap nonfullerene acceptors (NFAs) has boosted the efficiency of organic solar cells (OSCs) over 19 %. The new features of high-performance NFAs, such as visible-NIR light absorption, moderate the highest occupied molecular orbitals (HOMO), and high crystallinity, require polymer donors with matching physical properties. This emphasizes the importance of methods that can effectively tune the physical properties of polymers. Owning to very small atom size and strongest electronegativity, the fluorination has been proved the most efficient strategy to regulate the physical properties of polymer donors, including frontier energy level, absorption coefficient, dielectric constant, crystallinity and charge transport. Owing to the success of fluorination strategy, the vast majority of high-performance polymer donors possess one or more fluorine atoms. In this review, the fluorination synthetic methods, the synthetic route of well-known fluorinated building blocks, the fluorinated polymers which are categorized by the type of donor or acceptor units, and the relationships between the polymer structures, properties, and photovoltaic performances are comprehensively surveyed. We hope this review could provide the readers a deeper insight into fluorination strategy and lay a strong foundation for future innovation of fluorinated polymers.

Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.

Despite the use of various therapies such as hematopoietic stem cell transplantation and chimeric antigen receptor T cell therapy (CAR-T), the prognosis of patients with acute myeloid leukemia (AML) is still generally poor. However, immunotherapy is currently a hot topic in the treatment of hematological tumors. Extracellular adenosine triphosphate (ATP) can be converted to adenosine diphosphate (ADP) via CD39, and ADP can be converted to adenosine via CD73, which can bind to P1 and P2 receptors to exert immunomodulatory effects. Research on the mechanism of the purinergic signaling pathway can provide a new direction for the treatment of AML, and inhibitors of this signaling pathway have been discovered by several researchers and gradually applied in the clinic. In this paper, the mechanism of the purinergic signaling pathway and its clinical application are described, revealing a new target for the treatment of AML and subsequent improvement in patient prognosis.

Comprehensive mapping of immune perturbations associated with aplastic anemia.

BACKGROUND: Aplastic anemia (AA) is an immune-mediated syndrome characterized by bone marrow failure. Therefore, comprehending the cellular profile and cell interactions in affected patients is crucial. METHODS: Human peripheral blood mononuclear cells (PBMCs) were collected from both healthy donors (HDs) and AA patients, and analyzed using multicolor flow cytometry. Utilizing the FlowSOM and t-SNE dimensionality reduction technique, we systematically explored and visualized the major immune cell alterations in AA. This analysis provided a foundation to further investigate the subtypes of cells exhibiting significant changes. RESULTS: Compared to HDs, peripheral blood from patients with AA exhibits a marked reduction in CD56Dim natural killer (NK) cells, which also show diminished functionality. Conversely, an increase in NK-like CD56+ monocytes, which possess compromised functionality. Along with a significant reduction in myeloid-derived suppressor cells (MDSCs), which show recovery post-treatment. Additionally, MDSCs serve as effective clinical markers for distinguishing between acquired aplastic anemia (AAA) and congenital aplastic anemia (CAA). Our comprehensive analysis of correlations among distinct immune cell types revealed significant associations between NKBri cells and CD8+ T cell subsets, as well as between NKDim cells and CD4+ T cells, these results highlight the intricate interactions and correlations within the immune cell network in AA. CONCLUSION: Our study systematically elucidates the pronounced immune dysregulation in patients with AA. The detailed mapping of the immune landscape not only provides crucial insights for basic research but also holds promise for enhancing the accuracy of diagnoses and the effectiveness of timely therapeutic interventions in clinical practice. Consequently, this could potentially reduce the high mortality rate associated with AA.

Effect of glutathione-assisted continuous renal replacement therapy in sepsis patients with acute renal injury.

This study explored the effect of glutathione assisted continuous renal replacement therapy (CRRT) on peripheral blood receptors in sepsis patients with acute kidney injury. A total of 196 sepsis patients with acute kidney injury were recruited to perform a retrospective cohort study, 98 patients treated with glutathione combined with CRRT were included as the combination group, and then 98 patients treated with CRRT alone were included as the control group during the same period. The outcome was changes in the levels of blood urea nitrogen (BUN), serum creatinine (Scr), peripheral blood receptors, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment (SOFA) before and after treatment. After treatment, the levels of BUN and Scr in both groups of patients were significantly lower than those before treatment, and the levels in the combination group were lower than those in the control group. After treatment, toll-like receptor (TLR) 4 and TLR2 levels in both groups of patients were lower than those before treatment, and the levels in the combination group were lower than those in the control group. After treatment, the APACHE II and SOFA scores of the two groups were lower than those before treatment, and the scores in the combination group were lower than those in the control group. Glutathione-assisted CRRT can improve the renal function of patients and reduce the immune inflammatory response of sepsis patients with acute kidney injury, which can be widely promoted in the clinic.

Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis.

Background Type 2 Diabetes Mellitus (T2DM) frequently coexists with osteoporosis and reduced bone mineral density (BMD). Dipeptidyl peptidase-4 inhibitors (DPP-4i), a class of antihyperglycemic agents, are commonly employed in T2DM treatment. However, the influence of DPP-4i on bone health remains unclear and debated. This meta-analysis is conducted to explore the relationship between the use of DPP-4i and changes in BMD, as well as the prevalence of osteoporosis among T2DM patients. Methods We conducted a comprehensive search in PubMed, Embase, and Cochrane Library and Web of Science databases for relevant studies published up until June 2023. Studies included in the meta-analysis were those investigating T2DM patients under DPP-4i treatment, and examining the effects on BMD and osteoporosis. Random-effects models and fixed-effect models were utilized to compute the pooled effects. Heterogeneity among the included studies was evaluated using I² statistics. Results This meta-analysis incorporated a total of 10 studies, encompassing a combined population of 214,541 individuals. The results from this meta-analysis indicated an increase in BMD following DPP-4i usage (SMD 0.15, 95 % confidence interval 0.03-0.26). Additionally, the risk of osteoporosis was significantly reduced (OR 0.90, 95 % confidence interval 0.86-0.94) with very low heterogeneity, recorded at 0 % and 53.0 % respectively. No publication bias was detected in the funnel plot, and sensitivity analyses affirmed the stability of the study's conclusions. Conclusion Our results offer valuable insights into the positive impact of DPP-4i on bone health in T2DM patients, contributing to informed clinical decision-making. These findings may inform the development of more comprehensive T2DM management strategies that account for bone health.

Microflora structure and functional capacity in Tibetan kefir grains and selenium-enriched Tibetan kefir grains: A metagenomic analysis.

Tibetan kefir grains (TKGs) are a complex protein-lipid-polysaccharide matrix composed of various microorganisms. Microorganisms have the benefit of being effective, secure, and controllable when used for selenium enrichment. In this study, selenium-enriched Tibetan kefir grains (Se-TKGs) were made, and the microbiology composition was analyzed through a metagenomic analysis, to explore the influence of selenium enrichment. The microbial composition of TKGs and Se-TKGs, as well as the probiotic species, quorum sensing system (QS) and functional genes were compared and evaluated. Lactobacillus kefiranofaciens was the most abundant microbial species in both communities. Compared with TKGs, Se-TKGs had a much higher relative abundance of acetic acid bacteria. Lactobacillus helveticus was the most common probiotic species both in TKGs and Se-TKGs. Probiotics with antibacterial and anti-inflammatory properties were more abundant in Se-TKGs. QS analysis revealed that Se-TKGs contained more QS system-associated genes than TKGs. Moreover, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the pathway for human disease ko01501 had the greatest relative abundance in both TKGs and Se-TKGs. Compared with TKGs, Se-TKGs demonstrated a greater relative abundance of different drug resistance-related metabolic pathways. Additionally, linear discriminant analysis effect size was used to examine the biomarkers responsible for the difference between the two groups. In this study, we focused on the microbiological structure of TKGs and Se-TKGs, with the aim of establishing a foundation for a more thorough investigation of Se-TKGs and providing a basis for exploring potential future use.

Human health risks of heavy metal(loid)s mediated through crop ingestion in a coal mining area in Eastern China.

The heavy metal(loid)s (HMs) in soils can be accumulated by crops grown, which is accompanied by crop ingestion into the human body and then causes harm to human health. Hence, the health risks posed by HMs in three crops for different populations were assessed using Health risk assessment (HRA) model coupled with Monte Carlo simulation. Results revealed that Zn had the highest concentration among three crops; while Ni was the main polluting element in maize and soybean, and As in rice. Non-carcinogenic risk for all populations through rice ingestion was at an "unacceptable" level, and teenagers suffered higher risk than adults and children. All populations through ingestion of three crops might suffer Carcinogenic risk, with the similar order of Total carcinogenic risk (TCR): TCRAdults > TCRTeenagers > TCRChildren. As and Ni were identified as priority control HMs in this study area due to their high contribution rates to health risks. According to the HRA results, the human health risk was associated with crop varieties, HM species, and age groups. Our findings suggest that only limiting the Maximum allowable intake rate is not sufficient to prevent health risks caused by crop HMs, thus more risk precautions are needed.

Investigating the Effects and Mechanisms of Cyclomorusin on Osteoclasts in a High Glucose Environment.

Diabetes mellitus is an endocrine disease characterized by prolonged hyperglycemia. Prolonged high blood sugar levels interfere with the differentiation and maturation process of OBs and OCs, leading to the onset of osteoporosis. However, OCs differentiation and maturation is a complex regulatory process. In this study, we used a co-culture system of RAW264.7 and MC3T3-E1 cells under HG concentration to explore the effect of CYM on OCs in a HG environment. The effects of CYM on the formation and function of OCs were observed using TRAP-positive cell counts and bone resorption pits. Then, mRNA and protein expression levels of OCs-related genes were detected by real-time qPCR and western blotting. The results showed that CYM had an inhibitory effect on OCs differentiation and bone resorption, reduced mRNAs expression of OCs-associated genes, and downregulated RANKL/RANK/TRAF6 pathway that mediates OCs differentiation. CYM could be a promising natural compound against diabetic osteoporosis.

Multiple Primary Cavernous Hemangiomas of the Skull.

Multiple primary cavernous hemangiomas of the skull are exceedingly rare, with surgery often being the treatment of choice. The complexity of radiologic diagnosis means that the identification of these hemangiomas still largely depends on pathologic analysis. This article outlines the diagnostic and therapeutic journey of a 52-year-old female patient afflicted with multiple primary cavernous hemangiomas of the skull. Although the occurrence of multiple cavernous hemangiomas in this patient may seem fortuitous, the authors aim to contribute to understanding the pathogenesis of such conditions through this case report.

Family resilience, patient-reported symptoms in young stroke dyads: The effect of caregiver readiness and social support.

AIMS AND OBJECTIVES: To investigate empirically the direct effect and potential mechanism of family resilience on patient-reported outcomes among young stroke dyads in China. BACKGROUND: Young patients with stroke have been becoming an important public health issue. According to relevant theories and previous studies, we found that family resilience might play an important role in patient's symptoms. However, it is less clear about the specific relationship and potential mechanisms of these two variables. DESIGN: We used a prospective cross-sectional design. METHODS: A multi-item questionnaire was used to assess the constructs of interest. Researchers progressively constructed and validated conditional process models. The PROCESS macro was used to verify the research hypotheses. RESULTS: A total of 560 questionnaires were collected in this study. We found that family resilience of stroke patients and their spouses had a direct effect on the physical, psychological and social aspects of patient-reported symptoms. We further revealed that caregiver preparedness partially mediated the relationship between family resilience and patient's symptoms in stroke patient-spouse dyads, while perceived social support moderated the relationship between caregiver preparedness and patient's symptoms. Finally, we observed that the impact of caregiver readiness and social support on patients' symptoms predominantly manifested in physical and physiological outcomes. CONCLUSIONS: Our research provides evidence about the positive impact of family resilience on patient-reported symptoms in young stroke dyads. Meanwhile, it further revealed how caregiver preparedness and perceived social support may play out in the relationship. PRACTICE IMPLICATIONS: Our research introduces a novel perspective and pathway to enhance short-term recovery outcomes for patients. It also furnishes clinicians and nurses with evidence to guide the implementation of interventions aimed at improving patient health outcomes and facilitating smoother transitions from the hospital to home. IMPACT: What problem did the study address? Families play a crucial role in a patient's recovery process from illness, with family resilience serving as an important force for families to overcome adversity. However, the impact on patient symptoms and the underlying mechanisms of this relationship are uncertain. Empirical research is required to validate these aspects. What were the main findings? Family resilience has a positive impact on the physical, psychological and social aspects of patient-reported symptoms in young stroke dyads. Both the actor effect and partner effect are supported. The impact of caregiver readiness and social support on patient-reported symptoms is primarily observed in physical and physiological outcomes. Where and on whom will the research have an impact? This study offers a novel approach to enhance the short-term recovery of stroke patients. The researchers believe that the findings of this study will play an even more significant role during patients' transition from the hospital to home. REPORTING METHOD: This study followed the STROBE statement of cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: The study was conducted by patients, their spouses, healthcare professionals and the research team.

Molecular Characterization of Chemosensory Protein (CSP) Genes and the Involvement of AgifCSP5 in the Perception of Host Location in the Aphid Parasitoid Aphidius gifuensis.

Aphidius gifuensis is the dominant parasitic natural enemy of aphids. Elucidating the molecular mechanism of host recognition of A. gifuensis would improve its biological control effect. Chemosensory proteins (CSPs) play a crucial role in insect olfactory systems and are mainly involved in host localization. In this study, a total of nine CSPs of A. gifuensis with complete open reading frames were identified based on antennal transcriptome data. Phylogenetic analysis revealed that AgifCSPs were mainly clustered into three subgroups (AgifCSP1/2/7/8, AgifCSP3/9, and AgifCSP4/5/6). AgifCSP2/5 showed high expression in the antennae of both sexes. Moreover, AgifCSP5 was found to be specifically expressed in the antennae. In addition, fluorescent binding assays revealed that AifCSP5 had greater affinities for 7 of 32 volatile odor molecules from various sources. Molecular docking and site-directed mutagenesis results revealed that the residue at which AgifCSP5 binds to these seven plant volatiles is Tyr75. Behavior tests further confirmed that trans-2-nonenal, one of the seven active volatiles in the ligand binding test, significantly attracted female adults at a relatively low concentration of 10 mg/mL. In conclusion, AgifCSP5 may be involved in locating aphid-infested crops from long distances by detecting and binding trans-2-nonenal. These findings provide a theoretical foundation for further understanding the olfactory recognition mechanisms and indirect aphid localization behavior of A. gifuensis from long distances by first identifying the host plant of aphids.

A "Prediction - Detection - Judgment" framework for sudden water contamination event detection with online monitoring.

The contamination detection technology helps in water quality management and protection in surface water. It is important to detect sudden contamination events timely from dynamic variations due to various interference factors in online water quality monitoring data. In this study, a framework named "Prediction - Detection - Judgment" is proposed with a method framework of "Time series increment - Hierarchical clustering - Bayes' theorem model". Time to detection is used as an evaluation index of contamination detection methods, along with the probability of detection and false alarm rate. The proposed method is tested with available public data and further applied in a monitoring site of a river. Results showed that the method could detect the contamination events with a 100% probability of detection, a 17% false alarm rate and a time to detection close to 4 monitoring intervals. The proposed index time to detection evaluates the timeliness of the method, and timely detection ensures that contamination events can be responded to and dealt with in time. The site application also demonstrates the feasibility and practicability of the framework proposed in this study and its potential for extensive implementation.

Breast Cancer Screening in the Intermediate-Risk Population: Falling Through the Cracks?

Breast cancer screening guidelines vary for women at intermediate risk (15%-20% lifetime risk) for developing breast cancer across jurisdictions. Currently available risk assessment models have differing strengths and weaknesses, creating difficulty and ambiguity in selecting the most appropriate model to utilize. Clarifying which model to utilize in individual circumstances may help determine the best screening guidelines to use for each individual.

Photocatalytic CO2 Reduction by Near-Infrared-Light (1200†nm) Irradiation and a Ruthenium-Intercalated NiAl-Layered Double Hydroxide.

Near-infrared light-driven photocatalytic CO2 reduction (NIR-CO2PR) holds tremendous promise for the production of valuable commodity chemicals and fuels. However, designing photocatalysts capable of reducing CO2 with low energy NIR photons remains challenging. Herein, a novel NIR-driven photocatalyst comprising an anionic Ru complex intercalated between NiAl-layered double hydroxide nanosheets (NiAl-Ru-LDH) is shown to deliver efficient CO2 photoreduction (0.887 µmol h-1) with CO selectivity of 84.81 % under 1200 nm illumination and excellent stability over 50 testing cycles. This remarkable performance results from the intercalated Ru complex lowering the LDH band gap (0.98 eV) via a compression-related charge redistribution phenomenon. Furthermore, transient absorption spectroscopy data verified light-induced electron transfer from the Ru complex towards the LDH sheets, increasing the availability of electrons to drive CO2PR. The presence of hydroxyl defects in the LDH sheets promotes the adsorption of CO2 molecules and lowers the energy barriers for NIR-CO2PR to CO. To our knowledge, this is one of the first reports of NIR-CO2PR at wavelengths up to 1200 nm in LDH-based photocatalyst systems.

Breaking the Scaling Relationship in C-N Coupling via the Doping Effects for Efficient Urea Electrosynthesis.

Electrochemical C-N coupling reaction based on carbon dioxide and nitrate have been emerged as a new "green synthetic strategy" for the synthesis of urea, but the catalytic efficiency is seriously restricted by the inherent scaling relations of adsorption energies of the active sites, the improvement of catalytic activity is frequently accompanied by the decrease in selectivity. Herein, a doping engineering strategy was proposed to break the scaling relationship of intermediate binding and minimize the kinetic barrier of C-N coupling. A thus designed SrCo0.39Ru0.61O3-δ catalyst achieves a urea yield rate of 1522 µg h-1 mgcat. -1 and faradic efficiency of 34.1 % at -0.7 V versus reversible hydrogen electrode. A series of characterizations revealed that Co doping not only induces lattice distortion but also creates rich oxygen vacancies (OV) in the SrRuO3. The oxygen vacancies weaken the adsorption of *CO and *NH2 intermediates on the Co and Ru sites respectively, and the strain effects over the Co-Ru dual sites promoting the occurrence of C-N coupling of the two monomers instead of selective hydrogenating to form by-products. This work presents an insight into molecular coupling reactions towards urea synthesis via the doping engineering on SrRuO3.

Highly Enhanced Chloride Adsorption Mediates Efficient Neutral CO2 Electroreduction over a Dual-Phase Copper Catalyst.

Electrocatalytic carbon dioxide reduction (CO2R) in neutral electrolytes can mitigate the energy and carbon losses caused by carbonate formation but often experiences unsatisfied multicarbon selectivity and reaction rates because of the kinetic limitation to the critical carbon monoxide (CO)-CO coupling step. Here, we describe that a dual-phase copper-based catalyst with abundant Cu(I) sites at the amorphous-nanocrystalline interfaces, which is electrochemically robust in reducing environments, can enhance chloride-specific adsorption and consequently mediate local *CO coverage for improved CO-CO coupling kinetics. Using this catalyst design strategy, we demonstrate efficient multicarbon production from CO2R in a neutral potassium chloride electrolyte (pH ∼6.6) with a high Faradaic efficiency of 81% and a partial current density of 322 milliamperes per square centimeter. This catalyst is stable after 45 h of operation at current densities relevant to commercial CO2 electrolysis (300 mA per square centimeter).