DUS4L suppresses invasion and metastasis in LUAD via modulation of PI3K/AKT and ERK/MAPK signaling through GRB2.

OBJECTIVE: Limited research has focused on the role of dihydrouridine synthases (DUS) family members in human tumors. Our previous findings indicated an impact of dihydrouridine synthase 4 like (DUS4L) on cell proliferation and apoptosis in lung adenocarcinoma (LUAD) A549 cell, yet its broader functions and regulatory mechanisms in LUAD remain elusive. METHODS: Using a LUAD tissue microarray and immunohistochemical (IHC) staining, we validated variations in DUS4L protein expression levels among LUAD patients and assessed its clinical significance. Additional experiments using short hairpin RNA (shRNA) against DUS4L (sh-DUS4L-2), LUAD cell lines, cell function assays (including wound healing, transwell migration and invasion, colony formation, and apoptosis assays), and mouse tumor xenografts were performed to examine the biological roles of DUS4L in LUAD progression. RNA sequencing, proteomic analyses, mass spectrometry, and co-immunoprecipitation experiments were conducted to identify and validate DUS4L-regulated downstream target genes and signaling pathways. RESULTS: We identified a consistent upregulation of DUS4L in LUAD tissues. In vitro and in vivo experiments underscored the inhibitory effect of DUS4L downregulation on LUAD progression, including migration, invasion, and proliferation. Mechanistically, DUS4L was found to interact with the signaling molecule GRB2, promoting LUAD progression and metastasis by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK/MAPK pathways. CONCLUSION: Our results establish the functional role of DUS4L in driving the progression and metastasis of LUAD, implicating its potential as a candidate therapeutic target for LUAD.

Establishment of cerebral perfusion in a rat model with extracorporeal life support.

Background: Extracorporeal life support echniques as an Adjunct to Advanced Cardiac Life Support is usually suitable for complex heart surgery such as cardiopulmonary bypass (CPB). Cerebral perfusion is a clinically feasible neuroprotective strategy; however, the lack of a reliable small animal model.Methods: Based on the rat model of ECLS we evaluate the effects of ECLS-CP using HE staining, Nissl staining, TUNEL staining and ELISA.Result: We found that ECLS combined with the cerebral perfusion model did not cause brain injury and immune inflammation. There was no difference between the two by a left carotid artery or right carotid artery CP.Conclusion: These experimental results can provide the experimental basis for selecting blood vessels for ECLS patients and clinical CP to offers a trustworthy animal model for future exploration of applying brain perfusion strategies during ECLS-CP.

Decreased resting-state brain function in older adults predicts enlarged representational momentum.

Representational momentum (RM) refers to the phenomenon in which an observer's judgment of the final location of a previously viewed moving target is often displaced forward in the direction of motion. This phenomenon is an adaptive mechanism that compensates for neural processing delays and is closely associated with visual cortex function. However, the impact of age-related decline of visual cortex function on the manifestations of RM remains unclear. The present study examined differences in the RM effect between older (N = 82) and younger adults (N = 74) using a cursor-positioning task. Additionally, resting-state functional magnetic resonance imaging was used to explore the potential neural substrates that underlie these differences, employing amplitude of low-frequency fluctuation (ALFF, reflecting the intensity of neural activity) and regional homogeneity (ReHo, reflecting the synchronization of neural activity) as indicators. Our findings indicate a significant increase in RM among older adults compared with younger adults. Neuroimaging data revealed a significant decrease in ALFF and ReHo within extensive regions of the visual cortex in older adults, validating age-related differences in this cortical area. More importantly, ALFF values in the bilateral visual area 3 and ReHo values in the bilateral visual area 2 in older adults exhibited a strong negative correlation with their RM effects. These results suggest that larger RM in older adults may be functional compensation for aging of the visual cortex. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Magnetic fields promote electrocatalytic CO2 reduction via subtle modulations of magnetic moments and molecular bonding.

Introducing a magnetic-field gradient into an electrically driven chemical reaction is expected to give rise to intriguing research possibilities. In this work, we elaborate on the modes and mechanisms of electrocatalytic activity (from the perspective of alignment of magnetic moments) and selectivity (at the molecular level) for the CO2 reduction reaction in response to external magnetic fields. We establish a positive correlation between magnetic field strengths and apparent current densities. This correlation can be rationalized by the formation of longer-range ordering of magnetic moments and the resulting decrease in the scattering of conduction electrons and charge-transfer resistances as the field strength increases. Furthermore, aided by the magnetic-field-equipped operando infrared spectroscopy, we find that applied magnetic fields are capable of weakening the C-O bond strength of the key intermediate ∗COOH and elongating the C-O bond length, thereby increasing the faradaic efficiency for the electroreduction of CO2 to CO.

Rebaudioside B Attenuates Lung Ischemia-reperfusion Injury Associated Apoptosis and Inflammation.

OBJECTIVE: At present, no proven effective treatment is available for Lung Ischemiareperfusion Injury (LIRI). Natural compounds offer promising prospects for developing new drugs to address various diseases. This study sought to explore the potential of Rebaudioside B (Reb B) as a treatment compound for LIRI, both in vivo and in vitro. METHODS: This study involved utilizing the human pulmonary alveolar cell line A549, consisting of epithelial type II cells, subjected to Oxygen-glucose Deprivation/recovery (OGD/R) for highthroughput in vitro cell viability screening. The aim was to identify the most promising candidate compounds. Additionally, an in vivo rat model of lung ischemia-reperfusion was employed to evaluate the potential protective effects of Reb B. RESULTS: Through high-throughput screening, Reb B emerged as the most promising natural compound among those tested. In the A549 OGD/R models, Reb B exhibited a capacity to enhance cell viability by mitigating apoptosis. In the in vivo LIRI model, pre-treatment with Reb B notably decreased apoptotic cells, perivascular edema, and neutrophil infiltration within lung tissues. Furthermore, Reb B demonstrated its ability to attenuate lung inflammation associated with LIRI primarily by elevating IL-10 levels while reducing levels of IL-6, IL-8, and TNF-α. CONCLUSION: The comprehensive outcomes strongly suggest Reb B's potential as a protective agent against LIRI. This effect is attributed to its inhibition of the mitochondrial apoptotic pathway and its ability to mitigate the inflammatory response.

Effectiveness of exercise-based cardiac rehabilitation for patients with left ventricular assist device: A systematic review and meta-analysis.

PURPOSE: Exercise-based cardiac rehabilitation (EBCR) improves functional capacity in heart failure (HF). However, data on the effect of EBCR in patients with advanced HF and left ventricular assist devices (LVADs) are limited. This meta-analysis aimed to evaluate the impact of EBCR on the functional ability of LVAD patients by comparing the corresponding outcome indicators between the EBCR and ST groups. METHODS: PubMed, Embase, Clinical Trials, and Cochrane Library databases were searched for studies assessing and comparing the effects of EBCR and standard therapy (ST) in patients following LVAD implantation. Using pre-defined criteria, appropriate studies were identified and selected. Data from selected studies were extracted in a standardized fashion, and a meta-analysis was performed using a fixed-effects model. The protocol was registered on INPLASY (202340073). RESULTS: In total, 12 trials involving 477 patients were identified. The mean age of the participants was 52.9 years, and 78.6% were male. The initiation of EBCR varied from LVAD implantation during the index hospitalization to 11 months post-LVAD implantation. The median rehabilitation period ranged from 2 weeks to 18 months. EBCR was associated with improved peak oxygen uptake (VO2) in all trials. Quantitative analysis was performed in six randomized studies involving 214 patients (EBCR: n = 130, ST: n = 84). EBCR was associated with a significantly high peak VO2 (weighted mean difference [WMD] = 1.64 mL/kg/min; 95% confidence interval [CI], 0.20-3.08; p = .03). Similarly, 6-min walk distance (6MWD) showed significantly greater improvement in the EBCR group than in the ST group (WMD = 34.54 m; 95% CI, 12.47-56.42; p = .002) in 266 patients (EBCR, n = 140; ST, n = 126). Heterogeneity was low among the included trials. None of the included studies reported serious adverse events related to EBCR, indicating the safety of EBCR after LVAD implantation. CONCLUSION: This study demonstrated that EBCR following LVAD implantation is associated with greater improvement in functional capacity compared with ST as reflected by the improved peak VO2 and 6MWD values. Considering the small number of patients in this analysis, further research on the clinical impact of EBCR in LVAD patients is warranted.

Melittin kills A549 cells by targeting mitochondria and blocking mitophagy flux.

Melittin, a naturally occurring polypeptide found in bee venom, has been recognized for its potential anti-tumor effects, particularly in the context of lung cancer. Our previous study focused on its impact on human lung adenocarcinoma cells A549, revealing that melittin induces intracellular reactive oxygen species (ROS) burst and oxidative damage, resulting in cell death. Considering the significant role of mitochondria in maintaining intracellular redox levels and ROS, we further examined the involvement of mitochondrial damage in melittin-induced apoptosis in lung cancer cells. Our findings demonstrated that melittin caused changes in mitochondrial membrane potential (MMP), triggered mitochondrial ROS burst (Figure 1), and activated the mitochondria-related apoptosis pathway Bax/Bcl-2 by directly targeting mitochondria in A549 cells (Figure 2). Further, we infected A549 cells using a lentivirus that can express melittin-Myc and confirmed that melittin can directly target binding to mitochondria, causing the biological effects described above (Figure 2). Notably, melittin induced mitochondrial damage while inhibiting autophagy, resulting in abnormal degradation of damaged mitochondria (Figure 5). To summarize, our study unveils that melittin targets mitochondria, causing mitochondrial damage, and inhibits the autophagy-lysosomal degradation pathway. This process triggers mitoROS burst and ultimately activates the mitochondria-associated Bax/Bcl-2 apoptotic signaling pathways in A549 cells.

Neutrophil extracellular traps in acute coronary syndrome.

Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, which can cause heart failure, arrhythmia and even sudden death. It is the major cause of disability and death worldwide. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils activation and have various biological functions. NETs are closely related to the occurrence and development of ACS and also the subsequent damage after myocardial infarction. The mechanisms are complex and interdependent on various pathways, which require further exploration. This article reviewed the role and mechanism of NETs in ACS, thereby providing a valuable reference for the diagnosis and clinical treatment of ACS.

Efficacy of left subclavian artery revascularization strategies during thoracic endovascular aortic repair in patients with type B dissection: A single-center experience of 105 patients.

Background: Left subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method. Methods: In this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients. Results: The treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P < 0.05). The estimated blood loss, contrast agent volume, fluoroscopic time, operation time, and limb ischemia symptoms during the follow-up were significantly different in the four groups (P < 0.05). Pairwise comparison among groups indicated that the estimated blood loss and operation time in the CSB group were the highest (adjusted P < 0.0083; P < 0.05). The contrast agent volume and fluoroscopy duration were the highest in the SBSG groups, followed by PMF, CG, and CSB groups. The incidence of limb ischemia symptoms was the highest in the PMF group (28.6%) during the follow-up. The incidence of complications (except limb ischemia symptoms) during the perioperative and follow-up periods was similar among the four groups (P > 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P < 0.05), and the CSB group had the longest follow-up. Conclusion: Our single-center experience suggested that the PMF technique increased the risk of limb ischemia symptoms. The other three strategies effectively and safely restored LSA perfusion in patients with type B aortic dissection and had comparable complications. Overall, different LSA revascularization techniques have their advantages and disadvantages.

The relationship between childhood emotional neglect experience and depressive symptoms and prefrontal resting functional connections in college students: The mediating role of reappraisal strategy.

Childhood emotional neglect (CEN) has a relatively high incidence rate and substantially adverse effects. Many studies have found that CEN is closely related to emotion regulation and depression symptoms. Besides, the functional activity of the prefrontal lobe may also be related to them. However, the relationships between the above variables have not been thoroughly studied. This study recruited two groups of college students, namely, those with primary CEN (neglect group) and those without childhood trauma (control group), to explore the relationships among CEN, adulthood emotion regulation, depressive symptoms, and prefrontal resting functional connections. The methods used in this study included the Childhood Trauma Questionnaire (CTQ), Emotion Regulation Questionnaire (ERQ), Beck Depression Inventory-II (BDI-II) and resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared with the control group, the neglect group utilized the reappraisal strategy less frequently and displayed more depressive symptoms. The prefrontal functional connections with other brain regions in the neglect group were more robust than those in the control group using less stringent multiple correction standards. Across the two groups, the functional connection strength between the right orbitofrontal gyrus and the right middle frontal gyrus significantly negatively correlated with the ERQ reappraisal score and positively correlated with the BDI-II total score; the ERQ reappraisal score wholly mediated the relationship between the functional connection strength and the BDI-II total score. It suggests that primary CEN may closely correlate with more depressive symptoms in adulthood. Furthermore, the more robust spontaneous activity of the prefrontal lobe may also be closely associated with more depressive symptoms by utilizing a reappraisal strategy less frequently.

CytoSorb in patients with coronavirus disease 2019: A rapid evidence review and meta-analysis.

Background: After its approval by the European Union in 2011, CytoSorb therapy has been applied to control cytokine storm and lower the increased levels of cytokines and other inflammatory mediators in blood. However, the efficiency of this CytoSorb treatment in patients with coronavirus disease (COVID-19) still remains unclear. To elucidate the Cytosorb efficiency, we conducted a systematic review and single-arm proportion meta-analysis to combine all evidence available in the published literature to date, so that this comprehensive knowledge can guide clinical decision-making and future research. Methods: The literature published within the period 1 December 2019 to 31 December 2021 and stored in the Cochrane Library, Embase, PubMed, and International Clinical Trials Registry Platform (ICTRP) was searched for all relevant studies including the cases where COVID-19 patients were treated with CytoSorb. We performed random-effects meta-analyses by R software (3.6.1) and used the Joanna Briggs Institute checklist to assess the risk of bias. Both categorical and continuous variables were presented with 95% confidence intervals (CIs) as pooled proportions for categorical variables and pooled means for continuous outcomes. Results: We included 14 studies with 241 COVID-19 patients treated with CytoSorb hemadsorption. Our findings reveal that for COVID-19 patients receiving CytoSorb treatment, the combined in-hospital mortality was 42.1% (95% CI 29.5-54.6%, I2 = 74%). The pooled incidence of adjunctive extracorporeal membrane oxygenation (ECMO) support was 73.2%. Both the C-reactive protein (CRP) and interleukin-6 (IL-6) levels decreased after CytoSorb treatment. The pooled mean of the CRP level decreased from 147.55 (95% CI 91.14-203.96) to 92.36 mg/L (95% CI 46.74-137.98), while that of IL-6 decreased from 339.49 (95% CI 164.35-514.63) to 168.83 pg/mL (95% CI 82.22-255.45). Conclusions: The majority of the COVID-19 patients treated with CytoSorb received ECMO support. In-hospital mortality was 42.1% for the COVID-19 patients who had CytoSorb treatment. Both CRP and IL-6 levels decreased after Cytosorb treatment.

Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used in high-risk acute myocardial infarction (AMI) patients with promising outcomes. However, the underlying molecular mechanisms remain unknown and a VA-ECMO animal model has not yet been established. The purpose of this study was to establish a VA-ECMO model in AMI rats and evaluate long-term cardiac function. METHODS: We first established AMI in 20 Sprague-Dawley (SD) rats by ligating the left anterior descending coronary artery, while five rats underwent a thoracotomy to form the sham group. VA-ECMO was established after 30mins of AMI in 10 rats through the right jugular vein for venous drainage and right femoral artery for arterial infusion. Arterial blood pressure was monitored using a catheter in the left femoral artery, blood gas parameters were measured using a blood gas analyzer, while myocardial enzymes were detected using an ELISA Kit. Cardiac function was assessed through echocardiography on day 15. Masson staining and Western Blot were used for evaluating myocardial fibrosis, while histological injury was evaluated using hematoxylin and eosin staining. RESULTS: VA-ECMO support stabilized blood pressure, decreased the levels of myocardial enzymes including cTnI, cTnT, CK-MB, and was associated with a higher survival rate. In the long term, the VA-ECMO group showed improved cardiac function, significantly increased EF and FS but significantly decreased EDV and ESV compared to the AMI group. Furthermore, VA-ECMO significantly alleviated pathological damage and myocardial fibrosis. CONCLUSION: We established an economical, reliable, and reproducible VA-ECMO animal model in AMI rats, and demonstrated that VA-ECMO support prevents deteriorated cardiac function.

Venovenous extracorporeal membrane oxygenation for coronavirus disease 2019 patients: A systematic review and meta-analysis.

OBJECTIVE: Although the application of venovenous extracorporeal membrane oxygenation (VV-ECMO) in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS) is accumulating, the feasibility and safety of this therapy remain controversial. We aimed to evaluate the effect of VV-ECMO in the treatment of these patients. METHODS: A comprehensive literature search was performed using PubMed, Embase, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2021. According to the inclusion and exclusion criteria, the included studies were screened, and meta-analysis was performed by R software (version 4.0.2). RESULTS: Forty-two studies including 2037 COVID-19 patients supported with VV-ECMO due to ARDS were identified. The pooled analysis revealed that 30-, 60-, and 90-day mortality among patients were respectively 46% (95% CI 37%-57%, I2 = 66%), 46% (95% CI 30%-70%, I2 = 93%), and 49% (95% CI 43%-58%, I2 = 52%), and the pooled incidence rate of in-hospital mortality, major bleeding, hemorrhagic stroke, thrombosis, pulmonary embolism, deep venous thrombosis, and renal replacement therapy were respectively 35%, 39%, 11%, 40%, 15%, 21%, and 44%. CONCLUSION: Although COVID-19 patients may have a higher risk of bleeding, hemorrhagic stroke, and acute kidney injury during ECMO therapy, the survival rate was more than half of the cases. Our data may support the application of VV-ECMO in COVID-19 patients.

Del Nido cardioplegia for myocardial protection in adult cardiac surgery: a systematic review and update meta-analysis.

OBJECTIVE: Although the application of del Nido cardioplegia solution (DNC) in adult cardiac surgery is accumulating, the feasibility and safety of this myocardial protection strategy in adults remains controversial. We aimed to update our previous meta-analysis to determine the myocardial protective effect of DNC versus conventional cardioplegia (CC) in adult cardiac surgery. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2020. RESULTS: Thirty-seven observational studies and four randomized controlled trials (RCTs) including 21,779 patients were identified. The DNC group was associated with decreased postoperative cardiac enzymes [troponin T (cTnT) and creatine kinase-MB (CK-MB)] [standardized mean differences (SMD): -0.59, 95% confidence interval (CI): -0.99 to -0.19, p = 0.004], cardiopulmonary bypass (CPB) time (MD: -9.31, 95% CI: -13.10 to -5.51, p < 0.00001), aortic cross-clamp (ACC) time (MD: -7.20, 95% CI: -10.31 to -4.09, p < 0.00001), and cardioplegia volume (SMD: -1.95, 95% CI: -2.46 to -1.44, p < 0.00001). Intraoperative defibrillation requirement was less in the DNC group [relative risk (RR): 0.50, 95% CI: 0.33 to 0.75, p = 0.0007]. The pooled analysis revealed no significant difference in operative mortality among the patients assigned to DNC and those undergoing CC. CONCLUSION: In adult cardiac surgery, compared to CC, myocardial protection used with DNC yield similar or better short-term clinical outcomes. More high-quality trials and RCTs reflecting long-term follow-up morbidity and mortality are required in the future to confirm these findings.

Oroxin A ameliorates the oleic acid-induced A549 cell injury through the suppression of pyroptosis and degradation of alveolar surfactant.

The destruction of the pulmonary epithelial barrier in acute respiratory distress syndrome is caused by the damage of the alveolar epithelial cells. Oroxin A is an effective flavonoid component derived from the medicinal plant Oroxylum indicum (L.) Kurz. In this study, the oleic acid (OA)-induced A549 cell injury model was established in vitro to explore the protective mechanism of Oroxin A. The experiment was divided into the following groups: control, OA and OA + Oroxin A group. The OA-induced A549 cell injury was dose (time)-dependent and was detected by the CCK-8 assay. The protein and mRNA expression levels associated with pyroptosis are detected by Western blotting and RT-qPCR. After Oroxin A treatment, the levels of IL-1ß, IL-18 and LDH released were significantly lower than the OA group. In terms of pyroptosis, Oroxin A can inhibit the expression of pyroptosis-related protein and mRNA. Significantly, the surfactant protein C (SPC) level in the OA + Oroxin A group was significantly higher than that in the OA group. The treatment with Oroxin A alleviates the OA-induced injury in the A549 cells, and its mechanism may be related to the inhibition of A549 cells pyroptosis and prevention of the degradation of the SPC.

Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO.

INTRODUCTION: Although venovenous extracorporeal membrane oxygenation (VV ECMO) is a reasonable salvage treatment for acute respiratory distress syndrome (ARDS), it requires sedating the patient. Sevoflurane and propofol have pulmonary protective and immunomodulatory properties. This study aimed to compare the effectiveness of sevoflurane and propofol on rats with induced ARDS undergoing VV ECMO. METHODS: Fifteen sprague-dawley (SD) rats were randomly divided into three groups: Con group, sevoflurane (Sevo) group and propofol (Pro) group. Arterial blood gas tests were performed at time pointsT0 (baseline), T1 (the time to ARDS), and T2 (weaning from ECMO). Oxygenation index (PaO2/FiO2) was calculated, and lung edema assessed by determining the lung wet:dry ratio. The protein concentration in bronchial alveolar lavage fluid (BALF) was determined by using bicinchoninic acid assay. Haematoxylin and eosin staining was used to evaluate the lung pathological scores in each group. IL-1ß and TNF-α were also measured in the BALF, serum and lung. RESULTS: Oxygenation index showed improvement in the Sevo group versus Pro group. The wet:dry ratio was reduced in the Sevo group compared with propofol-treated rats. Lung pathological scores were substantially lower in the Sevo group versus the Pro group. Protein concentrations in the BALF and levels of IL-1ß and TNF-α in the Sevo group were substantially lower versus Pro group. CONCLUSION: This study demonstrates that compared with propofol, sevoflurane was more efficacious in improving oxygenation and decreasing inflammatory response in rat models with ARDS subject to VV ECMO treatment.

Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.

BACKGROUND: The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown. METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated. RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response. CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.

Dexamethasone Alleviates Myocardial Injury in a Rat Model of Acute Myocardial Infarction Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Myocardial ischemia causes myocardial inflammation. Research indicates that the venoarterial extracorporeal membrane oxygenation (VA ECMO) provides cardiac support; however, the inflammatory response caused by myocardial ischemia remains unresolved. Dexamethasone (Dex), a broad anti-inflammatory agent, exhibits a cardioprotective effect. This study aims to investigate the effect of Dex on a rat model of acute myocardial infarction (AMI) supported by VA ECMO. Male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: Sham group (n = 5), ECMO group (n = 6), and ECMO + Dex group (n = 6). AMI was induced by ligating the left anterior descending (LAD) coronary artery. Sham group only thoracotomy was performed but LAD was not ligated. The ECMO and ECMO + Dex groups were subjected to 1 h of AMI and 2 h of VA ECMO. In the ECMO + Dex group, Dex (0.2 mg/kg) was intravenously injected into the rats after 1 h of AMI. Lastly, myocardial tissue and blood samples were harvested for further evaluation. The ECMO + Dex group significantly reduced infarct size and levels of cTnI, cTnT, and CK-MB. Apoptotic cells and the expression levels of Bax, Caspase3, and Cle-Caspase3 proteins were markedly lower in the ECMO + Dex group than that in the ECMO group. Neutrophil and macrophage infiltration was lower in the ECMO + Dex group than in the ECMO group. A significant reduction was noted in ICAM-1, C5a, MMP-9, IL-1ß, IL-6, and TNF-α. In summary, our findings revealed that Dex alleviates myocardial injury in a rat model of AMI supported by VA ECMO.

Gadolinium Changes the Local Electron Densities of Nickel 3d Orbitals for Efficient Electrocatalytic CO2 Reduction.

Generally, in terms of electrocatalytic CO2 reduction, single-atom catalysts show high selectivities yet low current densities whereas conventional nanoparticle catalysts exhibit relatively high current densities but low selectivities. This work combines the advantages of the two classes of catalysts by constructing a Ni-Gd-N-doped carbon black electrocatalyst within which NiI active sites are exposed outside the carbon layers and Ni nanoparticles are encapsulated inside the carbon layers. The Gd atoms can not only influence the local electron densities of Ni 3d orbitals, thus strengthening the electronic activity, but also tailor the sizes of the Ni nanoparticles, thereby minimizing the activity toward hydrogen evolution. Accordingly, this electrocatalyst yields both a high CO faradaic efficiency (97 %) and a large current density (308 mA cm-2 ), alongside an outstanding stability (100 h).