ABSTRACT
Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , SARS-CoV-2 , mRNA Vaccines , Adult , Animals , Female , Humans , Male , Mice , 2019-nCoV Vaccine mRNA-1273/administration & dosage , 2019-nCoV Vaccine mRNA-1273/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Antibodies, Viral/blood , China , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cross Reactions/immunology , Epitopes, B-Lymphocyte/immunology , mRNA Vaccines/administration & dosage , mRNA Vaccines/genetics , mRNA Vaccines/immunology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , VaccinationABSTRACT
Transition metals and related compounds are known to exhibit high catalytic activities in various electrochemical reactions thanks to their intriguing electronic structures. What is lesser known is their unique role in storing and transferring electrons in battery electrodes which undergo additional solid-state conversion reactions and exhibit substantially large extra capacities. Here, a full dynamic picture depicting the generation and evolution of electrochemical interfaces in the presence of metallic nanoparticles is revealed in a model CoCO3/Li battery via an in situ magnetometry technique. Beyond the conventional reduction to a Li2CO3/Co mixture under battery operation, further decomposition of Li2CO3 is realized by releasing interfacially stored electrons from its adjacent Co nanoparticles, whose subtle variation in the electronic structure during this charge transfer process has been monitored in real time. The findings in this work may not only inspire future development of advanced electrode materials for next-generation energy storage devices but also open up opportunities in achieving in situ monitoring of important electrocatalytic processes in many energy conversion and storage systems.
ABSTRACT
Interfacial catalysis occurs ubiquitously in electrochemical systems, such as batteries, fuel cells, and photocatalytic devices. Frequently, in such a system, the electrode material evolves dynamically at different operating voltages, and this electrochemically driven transformation usually dictates the catalytic reactivity of the material and ultimately the electrochemical performance of the device. Despite the importance of the process, comprehension of the underlying structural and compositional evolutions of the electrode material with direct visualization and quantification is still a significant challenge. In this work, we demonstrate a protocol for studying the dynamic evolution of the electrode material under electrochemical processes by integrating microscopic and spectroscopic analyses, operando magnetometry techniques, and density functional theory calculations. The presented methodology provides a real-time picture of the chemical, physical, and electronic structures of the material and its link to the electrochemical performance. Using Co(OH)2 as a prototype battery electrode and by monitoring the Co metal center under different applied voltages, we show that before a well-known catalytic reaction proceeds, an interfacial storage process occurs at the metallic Co nanoparticles/LiOH interface due to injection of spin-polarized electrons. Subsequently, the metallic Co nanoparticles act as catalytic activation centers and promote LiOH decomposition by transferring these interfacially residing electrons. Most intriguingly, at the LiOH decomposition potential, electronic structure of the metallic Co nanoparticles involving spin-polarized electrons transfer has been shown to exhibit a dynamic variation. This work illustrates a viable approach to access key information inside interfacial catalytic processes and provides useful insights in controlling complex interfaces for wide-ranging electrochemical systems.
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Nanofluidic channels impose extreme confinement on water and ions, giving rise to unusual transport phenomena strongly dependent on the interactions at the channel-wall interface. Yet how the electronic properties of the nanofluidic channels influence transport efficiency remains largely unexplored. Here we measure transport through the inner pores of sub-1 nm metallic and semiconducting carbon nanotube porins. We find that water and proton transport are enhanced in metallic nanotubes over semiconducting nanotubes, whereas ion transport is largely insensitive to the nanotube bandgap value. Molecular simulations using polarizable force fields highlight the contributions of the anisotropic polarizability tensor of the carbon nanotubes to the ion-nanotube interactions and the water friction coefficient. We also describe the origin of the proton transport enhancement in metallic nanotubes using deep neural network molecular dynamics simulations. These results emphasize the complex role of the electronic properties of nanofluidic channels in modulating transport under extreme nanoscale confinement.
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Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.
Subject(s)
Embryo, Mammalian , Fertilization in Vitro , Embryo, Mammalian/metabolism , Epigenesis, Genetic , Histones/metabolism , Humans , Zygote/metabolismABSTRACT
Confined fluids and electrolyte solutions in nanopores exhibit rich and surprising physics and chemistry that impact the mass transport and energy efficiency in many important natural systems and industrial applications. Existing theories often fail to predict the exotic effects observed in the narrowest of such pores, called single-digit nanopores (SDNs), which have diameters or conduit widths of less than 10 nm, and have only recently become accessible for experimental measurements. What SDNs reveal has been surprising, including a rapidly increasing number of examples such as extraordinarily fast water transport, distorted fluid-phase boundaries, strong ion-correlation and quantum effects, and dielectric anomalies that are not observed in larger pores. Exploiting these effects presents myriad opportunities in both basic and applied research that stand to impact a host of new technologies at the water-energy nexus, from new membranes for precise separations and water purification to new gas permeable materials for water electrolyzers and energy-storage devices. SDNs also present unique opportunities to achieve ultrasensitive and selective chemical sensing at the single-ion and single-molecule limit. In this review article, we summarize the progress on nanofluidics of SDNs, with a focus on the confinement effects that arise in these extremely narrow nanopores. The recent development of precision model systems, transformative experimental tools, and multiscale theories that have played enabling roles in advancing this frontier are reviewed. We also identify new knowledge gaps in our understanding of nanofluidic transport and provide an outlook for the future challenges and opportunities at this rapidly advancing frontier.
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BACKGROUND AND AIMS: Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, previous studies only focused on baseline frailty status, not taking into consideration the changes in frailty status during follow-up. The aim of this study was to investigate the associations of changes in frailty status with incident CVD. METHODS: This study used data of three prospective cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), and Health and Retirement Study (HRS). Frailty status was evaluated by the Rockwood frailty index and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty status at baseline and the second survey which was two years after the baseline. Cardiovascular disease was ascertained by self-reported physician-diagnosed heart disease (including angina, heart attack, congestive heart failure, and other heart problems) or stroke. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. RESULTS: A total of 7116 participants from CHARLS (female: 48.6%, mean age: 57.4 years), 5303 from ELSA (female: 57.7%, mean age: 63.7 years), and 7266 from HRS (female: 64.9%, mean age: 65.1 years) were included according to inclusion and exclusion criteria. The median follow-up periods were 5.0 years in the CHARLS, 10.7 years in the ELSA, and 9.5 years in the HRS. Compared with stable robust participants, robust participants who progressed to pre-frail or frail status had increased risks of incident CVD (CHARLS, HR = 1.84, 95% CI: 1.54-2.21; ELSA, HR = 1.53, 95% CI: 1.25-1.86; HRS, HR = 1.59, 95% CI: 1.31-1.92). In contrast, frail participants who recovered to robust or pre-frail status presented decreased risks of incident CVD (CHARLS, HR = 0.62, 95% CI: 0.47-0.81; ELSA, HR = 0.49, 95% CI: 0.34-0.69; HRS, HR = 0.70, 95% CI: 0.55-0.89) when compared with stable frail participants. These decreased risks of incident CVD were also observed in pre-frail participants who recovered to robust status (CHARLS, HR = 0.66, 95% CI: 0.52-0.83; ELSA, HR = 0.65, 95% CI: 0.49-0.85; HRS, HR = 0.71, 95% CI: 0.56-0.91) when compared with stable pre-frail participants. CONCLUSIONS: Different changes in frailty status are associated with different risks of incident CVD. Progression of frailty status increases incident CVD risks, while recovery of frailty status decreases incident CVD risks.
Subject(s)
Cardiovascular Diseases , Frailty , Humans , Female , Aged , Middle Aged , Frailty/epidemiology , Cardiovascular Diseases/epidemiology , Longitudinal Studies , Prospective Studies , Frail ElderlyABSTRACT
Simultaneous detection of the concentration variations of microRNA-221 (miRNA-221) and PTEN mRNA molecules in the PI3K/AKT signaling pathway is of significance to elucidate cancer cell migration and invasion, which is useful for cancer diagnosis and therapy. In this work, we show the biodegradable MnO2 nanosheet-assisted and target-triggered DNAzyme recycling signal amplification cascaded approach for the specific detection of the PI3K/AKT signaling pathway in live cells via simultaneous and sensitive monitoring of the variation of intracellular miRNA-221 and PTEN mRNA. Our nanoprobes enable highly sensitive and multiplexed sensing of miRNA-221 and PTEN mRNA with low detection limits of 23.6 and 0.59 pM in vitro, respectively, due to the signal amplification cascades. Importantly, the nanoprobes can be readily delivered into cancer cells and the MnO2 nanosheets can be degraded by intracellular glutathione to release the Mn2+ cofactors to trigger multiple DNAzyme recycling cycles to show highly enhanced fluorescence at different wavelengths to realize sensitive and multiplexed imaging of PTEN mRNA and miRNA-221 for detecting the PI3K/AKT signaling pathway. Moreover, the regulation of PTEN mRNA expression by miRNA-221 upon stimulation by various drugs can also be verified by our method, indicating its promising potentials for both disease diagnosis and drug screening.
Subject(s)
DNA, Catalytic , MicroRNAs , MicroRNAs/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , DNA, Catalytic/metabolism , RNA, Messenger/genetics , Manganese Compounds , Oxides , Signal Transduction , Cell ProliferationABSTRACT
RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.
Subject(s)
Ischemic Stroke , Non-alcoholic Fatty Liver Disease , Renal Insufficiency, Chronic , Stroke , Humans , Cohort Studies , Overweight , Prospective Studies , Stroke/epidemiology , Stroke/etiology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiologyABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) stands as a persistent systemic inflammatory autoimmune condition. Despite this understanding, the precise impact of the systemic inflammation response index (SIRI) on the prognosis of RA patients remains elusive. This study aims to elucidate the correlation between the inflammatory biomarker SIRI and both all-cause mortality and cardiovascular mortality among RA patients. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020, a retrospective analysis was conducted. Survival data were depicted through Kaplan-Meier survival curves, while the relationship between SIRI and all-cause or cardiovascular mortality in RA patients was scrutinized via multivariable Cox proportional hazards regression analysis and restricted cubic spline plots. Furthermore, subgroup analysis and mediation analysis were also performed. RESULTS: This study encompassed 2656 RA patients with a comprehensive 20-year follow-up, during which 935 all-cause deaths and 273 deaths attributed to cardiovascular disease were recorded. We observed a nonlinear positive correlation between SIRI with both all-cause and cardiovascular mortality in RA patients. Notably, at a SIRI level of 1.12, the hazard ratio reached 1, indicating a shift from low to high mortality risk. Furthermore, mediation analysis revealed that 12.6% of the association between RA and mortality risk was mediated through SIRI. Subgroup analysis indicated a more pronounced association between SIRI and mortality in female patients or those with a high BMI. CONCLUSION: This study underscores a non-linear positive correlation between the biomarker SIRI and both all-cause mortality and cardiovascular mortality in RA patients.
Subject(s)
Arthritis, Rheumatoid , Cardiovascular Diseases , Inflammation , Nutrition Surveys , Humans , Arthritis, Rheumatoid/mortality , Female , Male , Cardiovascular Diseases/mortality , Middle Aged , Retrospective Studies , United States/epidemiology , Cause of Death , Biomarkers/blood , Adult , Proportional Hazards Models , Aged , Risk FactorsABSTRACT
Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata â × Channa argus â), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1ß, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.
Subject(s)
Bacterial Vaccines , Fish Diseases , Nocardia Infections , Nocardia , Vaccines, DNA , Animals , Nocardia/immunology , Nocardia Infections/veterinary , Nocardia Infections/immunology , Nocardia Infections/prevention & control , Fish Diseases/immunology , Fish Diseases/prevention & control , Vaccines, DNA/immunology , Bacterial Vaccines/immunology , Aldehyde-Lyases/genetics , Aldehyde-Lyases/immunology , Fishes/immunology , Bacterial Proteins/immunology , Bacterial Proteins/geneticsABSTRACT
Rare earth (RE) dopants can modulate the bandgap of oxides of indium and gallium and provide extra upconversion luminescence (UCL) abilities. However, relevant UCL fine-tuning strategies and energy mechanisms have been less studied. In this research, InGaO, Ho3+ monodoped and Yb3+/Ho3+ codoped In2O3, and Ho3+ monodoped Yb3Ga5O12 nanoparticles (NPs) were synthesized by a solvothermal method. The effects of Yb3+ and Ho3+ dopants on the crystal structures, UCL properties, and optical bandgaps of the oxides were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UCL spectroscopy, and measurements of decay times, pump power dependence, and transmittance spectra. The crystal structures of oxide products of indium and gallium were significantly modified with RE dopants. In2O3 and Yb3Ga5O12 were selected as the host materials. For Yb3+/Ho3+ codoped In2O3 NPs, there existed energy transfers from the defect states of In2O3 to Ho3+ and from Yb3+ to Ho3+. With a fixed Ho3+ concentration, In2O3:0%Yb3+,2%Ho3+ NPs showed the optimal UCL properties mainly due to In2O3-Ho3+ energy transfer and Ho3+-Yb3+ energy-back-transfer, while with a fixed Yb3+ concentration, In2O3:5%Yb3+,3%Ho3+ NPs with a slight Yb2O3 impurity and Yb3Ga5O12:2%Ho3+ NPs did mainly due to Ho3+-Ho3+ cross-relaxation. Besides, the optical bandgaps of In2O3 and Yb3Ga5O12 were noticeably broadened with RE dopants. These findings can offer feasible directions for the synthesis and UCL fine-tuning of RE-doped oxides of indium and gallium and improve their multifunction application prospects in the fields of semiconductor and UCL nanomaterials.
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BACKGROUND: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. METHODS AND RESULTS: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co-expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis-related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four-gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. CONCLUSION: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment.
Subject(s)
Ferroptosis , Humans , Ferroptosis/genetics , Alopecia/genetics , Alopecia/pathology , Fibrosis , Scalp/pathology , Gene Expression ProfilingABSTRACT
BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.
Subject(s)
Delirium , Hip Fractures , Hyperglycemia , Postoperative Complications , Humans , Hip Fractures/surgery , Hip Fractures/blood , Hyperglycemia/epidemiology , Hyperglycemia/blood , Female , Male , Retrospective Studies , Aged , Aged, 80 and over , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/blood , Delirium/blood , Delirium/epidemiology , Delirium/diagnosis , Delirium/etiology , Blood Glucose/metabolism , Blood Glucose/analysis , Preoperative Period , Incidence , Risk Factors , Propensity ScoreABSTRACT
BACKGROUND: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization. RESULTS: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05). CONCLUSIONS: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization.
Subject(s)
Endovascular Procedures , Ischemic Stroke , Medical Futility , Humans , Male , Female , Aged , Middle Aged , Ischemic Stroke/immunology , Ischemic Stroke/surgery , Ischemic Stroke/therapy , Registries , Aged, 80 and over , Inflammation/immunology , Prospective StudiesABSTRACT
A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.
Subject(s)
Colorimetry , Limit of Detection , Pesticides , Smartphone , Colorimetry/methods , Pesticides/analysis , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry , Malathion/analysis , Malathion/chemistry , Oxidoreductases/chemistry , Iron/chemistry , Acid Phosphatase/analysis , Acid Phosphatase/chemistry , BenzidinesABSTRACT
Twisted double bilayer graphene (tDBG) has emerged as a rich platform for studying strongly correlated and topological states, as its flat bands can be continuously tuned by both a perpendicular displacement field and a twist angle. Here, we construct a phase diagram representing the correlated and topological states as a function of these parameters, based on measurements of over a dozen tDBG devices encompassing two distinct stacking configurations. We find a hierarchy of symmetry-broken states that emerge sequentially as the twist angle approaches an apparent optimal value of θ ≈ 1.34°. Nearby this angle, we discover a symmetry-broken Chern insulator (SBCI) state associated with a band filling of 7/2 as well as an incipient SBCI state associated with 11/3 filling. We further observe an anomalous Hall effect at zero field in all samples supporting SBCI states, indicating spontaneous time-reversal symmetry breaking and possible moiré unit cell enlargement at zero magnetic field.
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Energy and the environment are the foundations of modern human society [...].
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Zn-MnO2 batteries have attracted extensive attention for grid-scale energy storage applications, however, the energy storage chemistry of MnO2 in mild acidic aqueous electrolytes remains elusive and controversial. Using α-MnO2 as a case study, we developed a methodology by coupling conventional coin batteries with customized beaker batteries to pinpoint the operating mechanism of Zn-MnO2 batteries. This approach visually simulates the operating state of batteries in different scenarios and allows for a comprehensive study of the operating mechanism of aqueous Zn-MnO2 batteries under mild acidic conditions. It is validated that the electrochemical performance can be modulated by controlling the addition of Mn2+ to the electrolyte. The method is utilized to systematically eliminate the possibility of Zn2+ and/or H+ intercalation/de-intercalation reactions, thereby confirming the dominance of the MnO2 /Mn2+ dissolution-deposition mechanism. By combining a series of phase and spectroscopic characterizations, the compositional, morphological and structural evolution of electrodes and electrolytes during battery cycling is probed, elucidating the intrinsic battery chemistry of MnO2 in mild acid electrolytes. Such a methodology developed can be extended to other energy storage systems, providing a universal approach to accurately identify the reaction mechanism of aqueous aluminum-ion batteries as well.
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BACKGROUND: Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS: We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program. RESULTS: In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14-1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35-21.28]). CONCLUSIONS: In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.