ABSTRACT
Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treat thrombotic disorders. It is also known to improve outcomes in sepsis, a leading cause of mortality resulted from infection-induced immune dysfunction. Whereas it is relatively clear how heparin exerts its anticoagulant effect, the immunomodulatory mechanisms enabled by heparin remain enigmatic. Here, we show that heparin prevented caspase-11-dependent immune responses and lethality in sepsis independent of its anticoagulant properties. Heparin or a chemically modified form of heparin without anticoagulant function inhibited the alarmin HMGB1-lipopolysaccharide (LPS) interaction and prevented the macrophage glycocalyx degradation by heparanase. These events blocked the cytosolic delivery of LPS in macrophages and the activation of caspase-11, a cytosolic LPS receptor that mediates lethality in sepsis. Survival was higher in septic patients treated with heparin than those without heparin treatment. The identification of this previously unrecognized heparin function establishes a link between innate immune responses and coagulation.
Subject(s)
Anticoagulants/therapeutic use , Caspases/metabolism , Heparin/therapeutic use , Macrophages/immunology , Sepsis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Caspases/genetics , Cell Line , Female , Glucuronidase/genetics , Glucuronidase/metabolism , Glycocalyx/metabolism , HMGB1 Protein/metabolism , Humans , Immunomodulation , Lipopolysaccharides/metabolism , Male , Mice , Mice, Knockout , Middle Aged , Sepsis/mortality , Survival Analysis , Young AdultABSTRACT
Plants respond to cold stress at multiple levels, including increasing cytosolic calcium (Ca2+) influx and triggering the expression of cold-responsive genes. Here we show that the Ca2+-permeable channel CYCLIC NUCLEOTIDE GATED CHANNEL20 (CNGC20) positively regulates freezing tolerance in Arabidopsis (Arabidopsis thaliana) by mediating cold-induced Ca2+ influx. Moreover, we demonstrate that the leucine-rich repeat receptor-like kinase PLANT PEPTIDE CONTAINING SULFATED TYROSINE1 RECEPTOR (PSY1R) is activated by cold, phosphorylating and enhancing the activity of CNGC20. The psy1r mutant exhibited decreased cold-evoked Ca2+ influx and freezing tolerance. Conversely, COLD-RESPONSIVE PROTEIN KINASE1 (CRPK1), a protein kinase that negatively regulates cold signaling, phosphorylates and facilitates the degradation of CNGC20 under prolonged periods of cold treatment, thereby attenuating freezing tolerance. This study thus identifies PSY1R and CRPK1 kinases that regulate CNGC20 activity and stability, respectively, thereby antagonistically modulating freezing tolerance in plants.
ABSTRACT
Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2â¢-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2â¢-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.
Subject(s)
Atherosclerosis , Cyclohexylamines , Ferroptosis , Phenylenediamines , Animals , Mice , Humans , Phospholipids , Phosphorylcholine , Phospholipid Ethers/metabolism , Phospholipid Ethers/pharmacology , Mice, Inbred C57BL , Human Umbilical Vein Endothelial Cells/metabolism , Endothelium/metabolism , Glutathione/metabolism , Iron/metabolism , Fatty Acid Binding Protein 3ABSTRACT
Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to investigate the mechanism by which ARMC10 regulation of mitochondrial dynamics affects mitochondrial function involved in ischaemic stroke (IS). Mitochondrial morphology was detected by laser scanning confocal microscopy (LSCM), and mitochondrial ultrastructural alterations were detected by electron microscopy. The expression of mitochondrial dynamics-related genes Drp1, Mfn1, Mfn2, Fis1, OPA1 and ARMC10 and downstream target genes c-Myc, CyclinD1 and AXIN2 was detected by RT-qPCR. Western blot was used to detect the protein expression of ß-catenin, GSK-3ß, p-GSK-3ß, Bcl-2 and Bax. DCFH-DA fluorescent probe was to detect the effect of ARMC10 on mitochondrial ROS level, Annexin V-FITC fluorescent probe was to detect the effect of ARMC10 on apoptosis, and ATP assay kit was to detect the effect of ARMC10 on ATP production. Mitochondrial dynamics was dysregulated in clinical IS samples and in the OGD/R cell model, and the relative expression of ARMC10 gene was significantly decreased in IS group (p < 0.05). Knockdown and overexpression of ARMC10 could affect mitochondrial dynamics, mitochondrial function and neuronal apoptosis. Agonist and inhibitor affected mitochondrial function and neuronal apoptosis by targeting Wnt/ß-Catenin signal pathway. In the OGD/R model, ARMC10 affected mitochondrial function and neuronal apoptosis through the mechanism that regulates Wnt/ß-catenin signalling pathway. ARMC10 regulates mitochondrial dynamics and protects mitochondrial function by activating Wnt/ß-catenin signalling pathway, to exert neuroprotective effects.
Subject(s)
Apoptosis , Armadillo Domain Proteins , Ischemic Stroke , Mitochondria , Mitochondrial Dynamics , Wnt Signaling Pathway , Humans , Armadillo Domain Proteins/metabolism , Armadillo Domain Proteins/genetics , beta Catenin/metabolism , beta Catenin/genetics , Brain Ischemia/metabolism , Brain Ischemia/genetics , Brain Ischemia/pathology , Ischemic Stroke/metabolism , Ischemic Stroke/genetics , Ischemic Stroke/pathology , Mitochondria/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Orphan nuclear estrogen-related receptor γ (ERRγ) has been recognized as a potential therapeutic target for cancer, inflammation and metabolic disorder. The ERRγ contains a regulatory AF2 helical tail linked C-terminally to its ligand-binding domain (LBD), which is a self-binding peptide (SBP) and serves as molecular switch to dynamically regulate the receptor alternation between active and inactive states by binding to and unbinding from the AF2-binding site on ERRγ LBD surface, respectively. Traditional ERRγ modulators are all small-molecule chemical ligands that can be classified into agonists and inverse agonists in terms of their action mechanism; the agonists stabilize the AF2 in ABS site with an agonist conformation, while the inverse agonists lock the AF2 out of the site to largely abolish ERRγ transcriptional activity. Here, a class of ERRγ peptidic antagonists was described to compete with native AF2 for the ABS site, thus blocking the active state of AF2 binding to ERRγ LBD domain. Self-inhibitory peptide was derived from the SBP-covering AF2 region and we expected it can rebind potently to the ABS site by reducing its intrinsic disorder and entropy cost upon the rebinding. Hydrocarbon stapling was employed to do so, which employed an all-hydrocarbon bridge across the [i, i + 4]-anchor residue pair in the N-terminal, middle or C-terminal region of the self-inhibitory peptide. As might be expected, it is revealed that the stapled peptides are good binders of ERRγ LBD domain and can effectively compete with the native AF2 helical tail for ERRγ ABS site, which exhibit a basically similar binding mode with AF2 to the site and form diverse noncovalent interactions with the site, thus conferring stability and specificity to the domain-peptide complexes.
ABSTRACT
BACKGROUND: We aimed to develop and validate a model to predict 1-year mortality risk among patients hospitalized for acute heart failure (AHF), build a risk score and interpret its application in clinical decision making. METHODS: By using data from China Patient-Centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for AHF in 52 hospitals across 20 provinces, we used multivariate Cox proportional hazard model to develop and validate a model to predict 1-year mortality. RESULTS: There were 4,875 patients included in the study, 857 (17.58%) of them died within 1-year following discharge of index hospitalization. A total of 13 predictors were selected to establish the prediction model, including age, medical history of chronic obstructive pulmonary disease and hypertension, systolic blood pressure, Kansas City Cardiomyopathy Questionnaire-12 score, angiotensin converting enzyme inhibitor or angiotensin receptor blocker at discharge, discharge symptom, N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, serum creatine, albumin, blood urea nitrogen, and highly sensitive C-reactive protein. The model showed a high performance on discrimination (C-index was 0.759 [95% confidence interval: 0.739, 0.778] in development cohort and 0.761 [95% confidence interval: 0.731, 0.791] in validation cohort), accuracy, calibration, and outperformed than several existed risk scores. A point-based risk score was built to stratify low- (0-12), intermediate- (13-16), and high-risk group (≥17) among patients. CONCLUSIONS: A prediction model using readily available predictors was developed and internal validated to predict 1-year mortality risk among patients hospitalized for AHF. It may serve as a useful tool for individual risk stratification and informing decision making to improve clinical care.
Subject(s)
Heart Failure , Hospitalization , Humans , Heart Failure/mortality , Male , Female , China/epidemiology , Aged , Risk Assessment/methods , Acute Disease , Hospitalization/statistics & numerical data , Prospective Studies , Middle Aged , Prognosis , Risk Factors , Proportional Hazards Models , Natriuretic Peptide, Brain/blood , Troponin T/blood , C-Reactive Protein/analysis , Peptide Fragments/bloodABSTRACT
Photocatalytic technology is a popular research area for converting solar energy into environmentally friendly chemicals and is considered the greenest approach for producing H2O2. However, the corresponding reactive oxygen species (ROS) and pathway involved in the photocatalytic generation of H2O2 by the Bi2.15WO6-glucose system are still not clear. Quenching experiments have established that neither â¢OH nor h+ contribute to the formation of H2O2, and show that the formed surface superoxo (≡Bi-OOâ¢) and peroxo (≡Bi-OOH) species are the predominant ROS in H2O2 generation. In addition, various characterizations indicate the enhanced electron-transfer on the surface of Bi2.15WO6 with increasing contents of glucose via the ligand-to-metal charge transfer pathway, confirming H-transfer from glucose to ≡Bi-OO⢠or ≡Bi-OOH. The increased production of H2O2 with decreasing bond dissociation energy (BDEO-H) values of various phenolic compounds again supports the H-transfer mechanism from phenolic compounds to ≡Bi-OO⢠and then to ≡Bi-OOH. DFT calculations further reveal that on the Bi2.15WO6 surface, oxygen is sequentially reduced to ≡Bi-OO⢠and ≡Bi-OOH, while H-transfer from H2O or glucose to ≡Bi-OO⢠and ≡Bi-OOH, resulting in the production of H2O2. The lower energy barrier of H-transfer from adsorbed glucose (0.636 eV) than that from H2O (1.157 eV) indicates that H-transfer is more favorable from adsorbed glucose. This work gives new insight into the photocatalytic generation of H2O2 by Bi2.15WO6 in the presence of glucose/phenolic compounds via the H-abstraction pathway.
ABSTRACT
BACKGROUND: To investigate the concurrent, long-term, and future adverse events and assess the trend of adverse events in pediatric patients with patent ductus arteriosus (PDA) after transcatheter closure. METHODS: A total of 1590 patients underwent transcatheter PDA closure were enrolled, including 465 patients (median age = 22 months) in the training group and 1125 patients in the validation group. Logistic regression analysis was used to assess independent risk factors associated with concurrent adverse events after closure. The chi-square test was used to evaluate the 5-year follow-up trend. RESULTS: Multivariable logistic regression analysis indicated that low age, female, and high pulmonary end diameter were independent risk factors for concurrent adverse events after closure. For patients without concurrent adverse events and for those who with concurrent adverse events but return to normal, the Chi-square test showed no abnormal results at the 5-year follow-up. Furthermore, the follow-up data of the validation group were not significantly different from those of the training group. CONCLUSION: The value of long-term follow-up of children may be limited for those who did not have a concurrent adverse event after closure nor for those who had a concurrent adverse event after closure but returned to normal during the 5-year follow-up period. IMPACT: Follow-up monitoring of adverse events tended to be recommended in pediatric patients with PDA after transcatheter closure. However, follow-up in these pediatric patients is expensive and there is a risk of sedation for echocardiography examination frequently. ·Patients who had no concurrent adverse events after closure did not show any abnormality at 5-year follow-up. ·Most of the patients who had concurrent adverse events after closure returned to normal at 5-year follow-up. The value of long-term follow-up may be limited for the above patients after transcatheter PDA closure.
ABSTRACT
HfO2-based ferroelectric materials as the most promising candidate for the ferroelectric memories, have been widely studied for more than a decade due to their excellent ferroelectric properties and CMOS compatibility. In order to realize its industrialization as soon as possible, researchers have been devoted to improving the reliability performance, such as wake up, imprint, limited endurance, et al. Among them, the breakdown characteristic is one of main failure mechanisms of HfO2-based ferroelectric devices, which limits the write/read reliability of the devices. Based on this, we systematically studied the effect of thickness on the time-dependent dielectric breakdown (TDDB) tolerate capability of HfO2-ZrO2(HZO) FE films under both forward and reverse electrical stress conditions. The thickness of HZO FE film ranged from 6 to 20 nm. Our findings reveal that decreasing the thickness of the HZO FE film leads to an improvement in TDDB tolerance capability which is attributed to the fact that higher density of oxygen vacancies in thinner HZO FE films can effectively inhibit the generation of new oxygen vacancies and the growth of conductive filaments, thus effectively improving the TDDB characteristics. These results provide a potential solution for mitigating breakdown characteristics of HfO2-based ferroelectric devices in memory applications.
ABSTRACT
Cyclic desulfurization-regeneration-denitrification based on metal-free carbon materials is one of the most promising ways to remove NOx and SO2 simultaneously. However, the impact of S-doping induced by the cyclic desulfurization and regeneration (C-S-R) process on the selective catalytic reduction (SCR) is not well understood. Herein, it is demonstrated that the C-S-R process at 500 °C induces in situ S-doping with a significant accumulation of C-S-C structures. NOx conversion was dramatically enhanced from 18.95% of the original sample to 84.55% of the S-doped sample. Density functional theory calculations revealed that the C-S-C structure significantly regulates the electronic structure of the C atom adjacent to the ketonic carbonyl group, thereby significantly altering the NH3 adsorption configuration with superior adsorption capacity. Moreover, S-doping induces an extra electron transfer between the N atom of the NH3 molecule and the C atom of the carbon plane, thereby promoting the activation of NH3 over the ketonic carbonyl group with a reduced energy barrier. This study elucidates a synergetic promotional mechanism between the ketonic carbonyl group and the C-S-C structure for SCR, offering a novel design strategy for high-performance heteroatom-doped carbon catalysts in industrial applications.
Subject(s)
Ammonia , Carbon , Oxidation-Reduction , Ammonia/chemistry , Metals , Titanium , CatalysisABSTRACT
The byproduct formation in environmental catalysis is strongly influenced by the chemical state and coordination of catalysts. Herein, two Pd/CeO2 catalysts (PdCe-350 and PdCe-800) with varying oxygen vacancies (Ov) and coordination numbers (CN) of Pd were prepared to investigate the mechanism of N2O and NH3 formation during NO reduction by CO. PdCe-350 exhibits a higher density of Ov and Pd sites with higher CN, leading to an enhanced metal-support interaction by electron transformation from the support to Pd. Consequently, PdCe-350 displayed increased levels of byproduct formation. In situ spectroscopies under dry and wet conditions revealed that at low temperatures, the N2O formation strongly correlated with the Ov density through the decomposition of chelating nitro species on PdCe-350. Conversely, at high temperatures, it was linked to the reactivity of Pd species, primarily facilitated by monodentate nitrates on PdCe-800. In terms of NH3 formation, its occurrence was closely associated with the activation of H2O and C3H6, since a water-gas shift or hydrocarbon reforming could provide hydrogen. Both bridging and monodentate nitrates showed activity in NH3 formation, while hyponitrites were identified as key intermediates for both catalysts. The insights provide a fundamental understanding of the intricate relationship among the local coordination of Pd, surface Ov, and byproduct distribution.
Subject(s)
Oxygen , Water , Oxidation-Reduction , Spectrum Analysis , Nitrates/chemistry , CatalysisABSTRACT
Carbon materials are regarded as a promising adsorbent for the adsorption of volatile organic compounds (VOCs). However, their adsorption behaviors are usually compromised at ambient conditions, attributed to the competitive VOCs adsorption with water vapor. In this study, we demonstrated that the selectivity for toluene than water of carbon can be effectively enhanced by introducing more sp2-carbon with two-dimensional nanosheets stacked. The multilayer carbon nanosheets enriched with sp2-carbon (CNS-MCA) exhibit a 151° H2O-contact angle, indicating hydrophobicity. Dynamic adsorption behaviors revealed that CNS-MCA retain 71% of their toluene adsorption capacity (91 mg/g) even at 60% relative humidity. Density functional theory (DFT) calculations, static adsorption studies, in situ Raman spectroscopy, and time-resolved in situ nuclear magnetic resonance (NMR) spectroscopy collectively indicate that toluene exhibits enhanced adsorption and selectivity due to π-π* interactions between its aromatic rings and the sp2-carbon. Conversely, water adsorption is attenuated, attributed to the reduced availability of surface-exposed hydrogen bonds associated with sp2-carbon and the inherent hydrophobic nature of multilayer graphene. This study extends a novel solution for the enhancement of VOCs adsorption under humid conditions.
ABSTRACT
The impact of water on catalyst activity remains inconclusive due to its dependence on the specific reaction environment. To maximize the exploitation of water's promoting effect, we employed ammonia selective catalytic reduction (NH3-SCR) as a probe reaction and proposed a phosphorus modification strategy for Cu-ZSM-5 catalysts. The objective of this approach was to construct water-adaptive microstructures through directional arrangement. To investigate the effect of phosphorus on the transformation of framework copper sites in humid environments, we conducted comprehensive characterizations and density functional theory calculation. Results reveal that water molecules cleave the oxygen bridges between phosphorus oxide and copper, leading to the formation of active isolated [Cu(OH)]+ groups and phosphate. The phosphate species weaken the interaction between exchanged Cu2+ groups and the zeolite framework, leading to the generation of highly migratory hydrated Cu2+ species. This work will potentially guide the rational design of water-adaptive catalysts for gas pollution abatement in a humid environment.
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BACKGROUND: Previous studies have examined anesthetics to improve postoperative prognosis after knee arthroscopic surgery. However, it is currently unknown whether perioperative anesthetics can influence postoperative hospital stay. We investigated the impact of esketamine after knee arthroscopic surgery on post-operative length of stay, fever and surgical site infection. METHODS: This study included 455 patients who underwent knee surgery between January2020 and August 2021at a tertiary hospital in China. Patient characteristics, preoperative laboratory values, intra-operative anesthetic data, and postoperative outcomes were collected. Univariate and multivariate logistic regression analyses with or without propensity score matching were performed to identify factors related to post-operative discharge within 3 days(PD3). RESULTS: A total of 297 cases met our inclusion criteria. The mean age of patients was 42 ± 14 years, mean body mass index, 24.1 ± 3.5 kg/m2, 157(53%) patients were male. Meniscus-related procedures accounted for the most part of all the procedures with a percentage of 40.4%, followed by combined procedures of 35.4%. After we adjusted for demographic and intraoperative characteristics with propensity score matching, esketamine use was significantly associated with PD3 with the highest odds ratio of 2.28 (95% confidence interval (CI): 1.18-4.41, p = 0.014). CONCLUSION: Esketamine use was associated with PD3 in patients underwent knee arthroscopic surgery. The findings of this study will be useful to anesthesiologists in making informed decisions regarding the choice of anesthetics for knee joint diseases. TRIAL REGISTRATION: This study was approved by the Ethics Committee (Approval No.:2023-041-01) of the Eighth Affiliated Hospital, Sun Yat-sen University and retrospectively registered.
Subject(s)
Anesthetics , Arthroscopy , Ketamine , Humans , Male , Adult , Middle Aged , Female , Cohort Studies , Length of Stay , Arthroscopy/methods , Propensity Score , Hospitals , Retrospective Studies , Postoperative Complications/etiologyABSTRACT
Beauveria bassiana is one of the most extensively studied entomopathogenic fungi (EPF) and is widely used as a biocontrol agent against various insect pests. Proteins containing the MARVEL domain are conserved in eukaryotes, typically with four transmembrane structures. In this study, we identified the five MARVEL domain proteins in B. bassiana. Five MARVEL domain proteins were localized to cytomembrane and vacuoles in B. bassiana, but had different roles in maintaining the lipid-droplet homeostasis. These proteins were required for fungal virulence, but differentially contributed to fungal utilization of nutrients, stress tolerance, and development under aerial and submerged conditions. Notably, BbMARVEL2 was essential for conidial surface morphology. Additionally, these five MARVEL domain proteins contributed to fungal interaction with the host immune defense. This study provides new mechanistic insights into the life cycle of B. bassiana as a biocontrol agent.
Subject(s)
Beauveria , Animals , Virulence , Fungal Proteins/metabolism , Insecta/microbiology , MARVEL Domain-Containing Proteins/metabolism , Spores, FungalABSTRACT
Cu-based catalysts possess great potential in the electrocatalytic nitrate (NO3-) reduction reaction for ammonia (NH3) synthesis. However, the low atomic economy limits their further application. Here we report a Cu single-atom (SA) incorporated in nitrogen-doped carbon (Cu SA/NC) with high atomic economy, which exhibits superior NH3 Faradaic efficiency (FE) of 100% along with an impressive NH3 yield rate of 7480 µg h-1 mgcat.-1. As counterparts, Cus+n/NC, with mixed SA and nanoparticles (NPs), shows decreasing NH3 FE with decreasing SA content, but the production of N2 and N2O increases gradually, which reaches the maximum on pure Cu NPs. In situ characterizations and theoretical calculations reveal that a higher NH3 FE of Cu SA/NC is ascribed to a lower free energy of the rate-limiting step (HNO* â N*) and effective inhibition for the N-N coupled process. This work provides the intuitive activity trends of Cu-based catalysts, opening an avenue for subsequent catalysts design.
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PURPOSE: Robot-assisted total knee arthroplasty (TKA) was developed to improve the precision and accuracy of implant placement in conventional TKA. However, the angular differences between referenced axes in robot-assisted TKA and conventional TKA remain unclear. The aim of this study was to investigate the angular differences in sagittal alignment between robot-assisted TKA and conventional TKA for both the femur and the tibia and to discuss their clinical implications. METHODS: We conducted a retrospective analysis of data from 100 patients (97 patients) who underwent computed tomography (CT) for Mako TKA. We measured the angle between the robot femoral axis (RFA) and conventional femoral axis (CFA) in the sagittal plane and the angle between the robot tibial axis (RTA) and the conventional tibial axis (CTA). Angles were compared between the sexes. Correlation analysis was conducted between the angles and height. RESULTS: In the sagittal plane, the mean RFA-CFA angle was 2.2° ± 1.6°, and the mean RTA-CTA angle was 2.3° ± 1.6°. There were no significant differences between the two angles among males and females (p > 0.05). There was a correlation between the RFA-CFA angle and RTA-CTA angle (p < 0.001, r = 0.33), and there was a correlation between height and the combination of the RFA-CFA angle and RTA-CTA angle (p = 0.03, r = 0.22). CONCLUSION: There are angular differences between the axes referenced by robot-assisted TKA and those referenced by conventional TKA, which may be influenced by patient height. Correctly understanding these differences is crucial when evaluating the implant position and surgical outcomes after robot-assisted TKA. Furthermore, caution should be taken when assessing the flexion-extension angle of the knee since the angles displayed in the Mako system are different from the angles measured with intramedullary anatomical axes. After all, sagittal alignment principles differ between robot-assisted and conventional TKA; however, further studies are required to determine which principle is more appropriate or to modify these principles.
Subject(s)
Arthroplasty, Replacement, Knee , Femur , Robotic Surgical Procedures , Tibia , Humans , Arthroplasty, Replacement, Knee/methods , Male , Female , Retrospective Studies , Aged , Tibia/surgery , Tibia/diagnostic imaging , Middle Aged , Femur/surgery , Femur/diagnostic imaging , Robotic Surgical Procedures/methods , Tomography, X-Ray Computed/methods , Knee Joint/surgery , Knee Joint/diagnostic imaging , Aged, 80 and over , Osteoarthritis, Knee/surgeryABSTRACT
BACKGROUND: Goat milk is considered a nutritionally superior resource, owing to its advantageous nutritional attributes. Nevertheless, it is susceptible to spoilage and the persistence of pathogens. Electron beam irradiation stands as a promising non-thermal processing technique capable of prolonging shelf life with minimal residue and a high degree of automation. RESULTS: The effects of electron beam irradiation (2, 3, 5, and 7 kGy) on microorganisms, physicochemical properties, and protein structure of goat milk compared with conventional pasteurized goat milk (PGM) was evaluated. It was found that a 2 kGy electron beam irradiation reduces the total microbial count of goat milk by 6-logs, and the irradiated goat milk protein secondary structure showed a significant decrease in É-helix content. Low irradiation doses led to microaggregation and crosslinking. In contrast, high doses (≥ 5 kGy) slightly disrupted the aggregates and decreased the particle size, disrupting the microscopic surface structure of goat milk, verified by scanning electron microscopy and confocal laser scanning microscopy. CONCLUSION: The irradiation of goat milk with a 2 kGy electron beam may effectively inactivate harmful microorganisms in the milk and maintain/or improve the physicochemical quality and protein structure of goat milk compared to thermal pasteurization. © 2024 Society of Chemical Industry.
Subject(s)
Electrons , Food Irradiation , Goats , Milk , Animals , Milk/microbiology , Milk/chemistry , Milk/radiation effects , Food Irradiation/methods , Milk Proteins/chemistry , Bacteria/radiation effects , Pasteurization/methods , Food MicrobiologyABSTRACT
As a traditional method of ammonia (NH3 ) synthesis, Haber-Bosch method expends a vast amount of energy. An alternative route for NH3 synthesis is proposed from nitrate (NO3 - ) via electrocatalysis. However, the structure-activity relationship remains challenging and requires in-depth research both experimentally and theoretically. Here an N-coordinated Cu-Ni dual-single-atom catalyst anchored in N-doped carbon (Cu/Ni-NC) is reported, which has competitive activity with a maximal NH3 Faradaic efficiency of 97.28%. Detailed characterizations demonstrate that the high activity of Cu/Ni-NC mainly comes from the contribution of Cu-Ni dual active sites. That is, (1) the electron transfer (Ni â Cu) reveals the strong electron interaction of Cu-Ni dual-single-atom; (2) the strong hybridizations of Cu 3d-and Ni 3d-O 2p orbitals of NO3 - can accelerate electron transfer from Cu-Ni dual-site to NO3 - ; (3) Cu/Ni-NC can effectively decrease the rate-limiting step barriers, suppress N-N coupling for N2 O and N2 formation and hydrogen production.
ABSTRACT
The present study aims to investigate the role of AKT2 in the pathogenesis of hepatic and cardiac lipotoxicity induced by lipid overload-induced obesity and identify its downstream targets. WT and Akt2 KO mice were fed either normal diet, or high-fat diet (HFD) to induce obesity model in vivo. Human hepatic cell line (L02 cells) and neonatal rat cardiomyocytes (NRCMs) were used as in vitro models. We observed that during HFD-induced obesity, Akt2 loss-of-function mitigated lipid accumulation and oxidative stress in the liver and heart tissue. Mechanistically, down-regulation of Akt2 promotes SIRT6 expression in L02 cells and NRCMs, the latter deacetylates SOD2, which promotes SOD2 activity and therefore alleviates oxidative stress-induced injury of hepatocytes and cardiomyocytes. Furthermore, we also proved that AKT2 inhibitor protects hepatocytes and cardiomyocytes from HFD-induced oxidative stress. Therefore, our work prove that AKT2 plays an important role in the regulation of obesity-induced lipid metabolic disorder in the liver and heart. Our study also indicates AKT2 inhibitor as a potential therapy for obesity-induced hepatic and cardiac injury.