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Citrus oil (CO) is a commonly used natural flavor with high volatility, which is not conducive to sustained release under food environmental stress. This study constructed novel ß-cyclodextrin/cationic cellulose nanocrystal (ß-CD/C-CNC) complexes via noncovalent interaction, which were used to stabilize CO-loaded Pickering emulsions (PEß-CD/C-CNC). The C-CNC greatly improved the physical stability, droplet dispersion and viscoelasticity of PEß-CD/C-CNC by forming a tight network structure, as verified by rheological behavior. Moreover, C-CNC improved the wettability of ß-CD/C-CNC complexes and enhanced the interaction between adjacent ß-CD/C-CNC complexes. C-CNC also contributed to the interfacial viscoelasticity, hydrated mass, and layer thickness via the interfacial dilational modulus and QCM-D. ß-CD/C-CNC complexes adsorbed on the oil-water interface gave rise to a dense filling layer as a physical barrier, enhancing the sustained-release performance of PEß-CD/C-CNC by limiting diffusion of citrus essential oil into the headspace. This study provides new technical approaches for aroma retention in the food industry.
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Compressed ternary alloy superhydrides are currently considered to be the most promising competitors for high-temperature superconducting materials. Here, the stable stoichiometries in the Y-Hf-H ternary system under pressure are comprehensively explored in theory and four fresh phases are predicted: Pmna-YHfH6 and P4/mmm-YHfH7 at 200 GPa, P4/mmm-YHfH8 at 300 GPa and P-6m2-YHfH18 at 400 GPa. The four Y-Hf-H ternary phases are thermodynamically and dynamically stable at corresponding pressure. In addition, structural features, bonding characteristics, electronic properties, and superconductivity of the four ternary Y-Hf-H phases are systematically calculated and discussed. As the hydrogen content and the density of states of H atoms at the Fermi level increase, the superconducting transition temperatures (Tc) of Y-Hf-H system are significantly enhanced. The P-6m2-YHfH18 with high hydrogen content exhibits a high calculated Tc value of 130 K at 400 GPa.
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Background: Limited and conflicting evidence exists for the associations between tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease (AD). This meta-analysis aimed to elucidate these associations and quantify potential dose-response relationships. Methods: PubMed, EMBASE, and Web of Science were searched up to 11 June 2024 for cohort studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs), with the dose-response relationship assessed using restricted cubic splines. The Grading of Recommendations Assessment Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: Our analysis encompassed 38 cohorts, totalling 751 824 participants and 13 017 dementia and 17 341 AD cases. For dementia, compared with the lowest category, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine were 0.84 (0.74-0.96, n = 6), 0.95 (0.87-1.02, n = 9), and 0.94 (0.70-1.25, n = 5), with all rated as low certainty in GRADE. For AD, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine compared to the lowest category were 0.93 (0.87-1.00, n = 6), 1.01 (0.90-1.12, n = 10), and 1.34 (1.04-1.74, n = 2), with certainty ratings of low, low, and very low, respectively. Dose-response analysis indicated a non-linear relationship between coffee intake (Poverall = 0.04 and Pnonlinear = 0.01) and dementia risk, showing the protective association of risk of dementia with 1 to 3 cups per day of coffee intake. There is a linear association between tea intake and risk of dementia, with a significantly decreased risk of dementia for each 1 cup per day increase in tea consumption (0.96, 95% CI 0.94-0.99, Poverall = 0.01 and Pnonlinear = 0.68). Conclusion: Increased tea consumption was associated with a decreased risk of dementia and AD, and a non-linear relationship was found between coffee and dementia, supporting public health recommendations for dementia prevention.
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Enfermedad de Alzheimer , Cafeína , Café , Demencia , Té , Té/química , Café/química , Humanos , Enfermedad de Alzheimer/prevención & control , Cafeína/administración & dosificación , Demencia/epidemiología , Demencia/prevención & control , Estudios de Cohortes , Femenino , Anciano , Masculino , Factores de RiesgoRESUMEN
Objective: To explore the impact of Liraglutide, a GLP-1 receptor agonist, on glycolipid metabolism and microinflammatory status in patients with abdominal obesity and type 2 diabetes. Methods: This study consecutively enrolled 60 patients with abdominal obesity and type 2 diabetes at Jiande Hospital of Traditional Chinese Medicine from October 2020 to December 2021. They were randomly divided into a control group (30 cases) receiving routine treatment and a liraglutide group (30 cases) receiving Liraglutide in addition to routine treatment for 3 months. The control group received routine treatment, which included metformin at a dose of 1g twice daily, along with dietary and exercise guidance. The liraglutide group received an initial dose of 0.6 mg daily for the first week, increased to 1.2 mg daily in the second week, and further increased to 1.8 mg daily in the third week, continuing at this dose until the end of the 12-week treatment period, with adjustments based on tolerance. Results: Significant improvements were observed in SBP, DBP, BMI, waist-to-hip ratio, and various glycolipid and microinflammatory indexes in the Liraglutide group compared to controls (P < .05). Specifically, SBP, DBP, BMI, waist-to-hip ratio, FPG, 2hPG, HbA1c, TG, TC, hs-CRP, TNF-α, and IL-6 levels decreased more significantly in the liraglutide group. Conversely, C-peptide and fasting insulin levels increased more in the liraglutide group. No significant difference in the incidence of adverse reactions was observed between the two groups (P > .05). Conclusion: Liraglutide can improve glycolipid metabolism and microinflammatory status in patients with abdominal obesity and type 2 diabetes, which has high medication safety.
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Deep network fault diagnosis methods heavily rely on abundant labeled data for effective model training. However, small-sized samples and imbalanced samples often lead to insufficient features, resulting in accuracy degradation and even instability in the diagnosis model. To address this challenge, this paper introduces a coupled adversarial autoencoder (CoAAE) based on the Bayesian method. This model aims to solve the issue of insufficient samples by generating fake samples and integrating them with the original ones. Within the CoAAE framework, the probability density distribution of the original data is captured using an encoder and fake samples are generated by random sampling from this distribution and decoding them. This process is the adversarial interaction between the encoder and a classifier to obtain the prior distribution of the encoder's parameters. The encoder's parameters are updated through the decoder's reconstruction process, leading to the posterior distribution. Concurrently, the decoder is trained to enhance its ability to reconstruct samples accurately. To address the imbalance in the original samples, a parallel coupled network is employed. This network shares the weights of the extraction layer in the encoder, enabling it to learn the joint distribution between fault-related and normal samples. To evaluate the effectiveness of the proposed data augmentation method, experiments were conducted on a bearing database from Case Western Reserve University using ResNet18 as the deep learning diagnosis model representative. The results demonstrate that CoAAE can effectively augment imbalanced datasets and outperform other advanced methods.
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Background: Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum. When severe, it greatly increases risk for later postpartum depression. This trial compared a dietary supplement to placebo on PPB severity. The supplement was designed to counter downstream effects of elevated monoamine oxidase A level, implicated in causing PPB. Methods: Participants recruited by advertisement from the Toronto region completed procedures at CAMH, Canada and/or participants' homes. Oral supplement or identical appearing relatively inert placebo were administered in randomised, double-blind fashion. Supplement was blueberry juice and extract given four times between nighttime day 3 and morning day 5 postpartum; tryptophan 2 g nighttime day 4 postpartum, and tyrosine 10 g morning day 5 postpartum. On day 5, depressed mood induction procedure (MIP) and postpartum blues were assessed. All data is presented (NCT03296956 closed, clinicaltrials.gov). Findings: Between January 2019 and December 2022, participants took supplement (n = 51) or placebo (n = 52). There was no significant effect on primary outcome MIP on visual analogue scale for depressed mood (mean difference = -0.39 mm, 95% CI: -6.42 to 5.65 mm). Stein Maternity Blues scores, exploratory PPB measure, was lower in the active group (effect size 0.62; median, interquartile range (IQR): active 2.00 (IQR 1, 4); placebo 4.00 (IQR 1.5, 6); regression with general linear model, supplement effect, ß coefficient = -1.50 (95%: CI -2.60, -0.40), p = 0.008; effect of CES-D crying category before supplement, p = 0.03-0.00000023). Twenty-six and 40 different adverse events occurred within 25% and 42% of supplement and placebo cases respectively (Chi-Square, p = 0.06). Interpretation: The primary outcome was negative for effect on depressed mood induction, however the supplement moderately reduced PPB. Funding: CAMH/Exeltis.
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Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.
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Desayuno , Enfermedades Cardiovasculares , Neoplasias , Humanos , Neoplasias/mortalidad , Enfermedades Cardiovasculares/mortalidad , Estudios Prospectivos , Adulto , Conducta Alimentaria , Masculino , Factores de Riesgo , Femenino , Persona de Mediana Edad , Ayuno IntermitenteRESUMEN
Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.
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Fluorodesoxiglucosa F18 , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , AdultoRESUMEN
This paper calculates the acoustic shadow zone of the guided wave in a variable thickness plate. The variable thickness plate has a wide range of applications in bridges, ships, etc., and the guided wave is often used for its nondestructive testing. The velocity gradient induced by thickness variations will deflect the guided wave towards lower phase velocities. Both frequency and thickness variation play crucial roles in determining the extent of path bending. In particular, the guided wave can undergo reverse propagation at the non-boundary of the plate. This curved propagation path results in an acoustic shadow zone, inaccessible to direct waves. This article calculates and experimentally verifies the curved propagation path of dispersive guided waves. Experiments show that the degree of propagation path bending increases with the increase of frequency in a certain frequency range. On the path that varies along the thickness, the experiment observes an acoustic shadow zone that accounts for nearly 25% of the total path. Additionally, a practical case study involving a guided wave with a curved path is presented. Consideration of the curved path improves the positioning accuracy, offering insights into damage location in variable thickness plates. This research on the propagation path and acoustic shadow zone contributes to advancing the understanding of guided wave propagation characteristics and enhancing their application in nondestructive testing for variable thickness structures.
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Two types of isostructural iron-cobalt/nickel-antimony-oxo tartrate cluster-based compounds, namely (H3O)(Me2NH2)[M(H2O)6]2[FeII2SbIII12(µ4-O)3(µ3-O)8(tta)6]·6H2O (M = Co (1); Ni (3)), H5/3[Co2.5FeII4/3FeIII3(H2O)13SbV1/3FeIII2/3(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (2) and H2[Ni2.25FeII1.5FeIII3(H2O)14SbV0.25FeIII0.75(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (4) (H4tta = tartaric acid) were synthesized via simple solvothermal reactions. All the clusters in the structures adopt sandwich configurations, that is, bilayer sandwich configuration in 1 and 3 and monolayer sandwich configuration in 2 and 4. Interestingly, the monolayer sandwiched compounds 2 and 4 represent rare examples of cluster-based compounds containing mixed-valence Sb(III, V), whose center of the intermediate layer is the co-occupied [FexSbV1-x]. This is different from that of previously reported sandwich-type antimony-oxo clusters in which the center position is either occupied by a transition metal ion or a Sb(V) alone. Thus, the discovery of title compounds 2 and 4 makes the evolution of center metal ion more complete, that is, from M, MxSbV1-x to SbV. All the title compounds were fully characterized, and the photocatalysis, proton conduction and magnetism of compounds 2 and 4 were studied.
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Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were -6.7% (SE 0.7) with mazdutide 3 mg, -10.4% (0.7) with 4.5 mg, -11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from -7.7% to -12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction.
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Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Humanos , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/inducido químicamente , Peso Corporal , Péptido 1 Similar al Glucagón/uso terapéutico , Método Doble Ciego , Resultado del TratamientoRESUMEN
To address the fuzzy reconstruction effect on distant objects in unbounded scenes and the difficulty in feature matching caused by the thin structure of power lines in images, this paper proposes a novel image-based method for the reconstruction of power transmission lines (PTLs). The dataset used in this paper comprises PTL progressive motion sequence datasets, constructed by a visual acquisition system carried by a developed Flying-walking Power Line Inspection Robot (FPLIR). This system captures close-distance and continuous images of power lines. The study introduces PL-NeRF, that is, an enhanced method based on the Neural Radiance Fields (NeRF) method for reconstructing PTLs. The highlights of PL-NeRF include (1) compressing the unbounded scene of PTLs by exploiting the spatial compression of normal L∞; (2) encoding the direction and position of the sample points through Integrated Position Encoding (IPE) and Hash Encoding (HE), respectively. Compared to existing methods, the proposed method demonstrates good performance in 3D reconstruction, with fidelity indicators of PSNR = 29, SSIM = 0.871, and LPIPS = 0.087. Experimental results highlight that the combination of PL-NeRF with progressive motion sequence images ensures the integrity and continuity of PTLs, improving the efficiency and accuracy of image-based reconstructions. In the future, this method could be widely applied for efficient and accurate 3D reconstruction and inspection of PTLs, providing a strong foundation for automated monitoring of transmission corridors and digital power engineering.
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This study investigates the utilization of a stepped wave frequency modulation jamming technique in radar systems. The objective is to enhance the effectiveness and robustness of false target jamming in the presence of linear frequency modulation (LFM) radars employing constant false alarm rate (CFAR) detection. The proposed method combines stepped frequency modulation with full pulse delay/sum repeat jamming to enhance resilience against uncertainties in target parameters. Theoretical analysis and simulation experiments are conducted to establish relationships between key jammer parameters, such as frequency slope and power compensation, and performance metrics, like false target distribution and CFAR masking. The results demonstrate that the proposed technique effectively maintains a dense distribution of false targets surrounding the protected target, even in the presence of uncertainties in position and signal-to-noise ratio. In comparison to existing methods, the utilization of stepped-waveform modulation enables improved control over target distribution and CFAR masking. Adaptive power allocation compensates for parameter errors, thereby enhancing robustness. Simulation results reveal that the proposed approach significantly reduces the probability of detecting the true target by over 95% under uncertain conditions, while previous methods experienced degradation. The integration of stepped waveforms optimizes false target jamming, thereby advancing electronic warfare capabilities in countering advanced radar threats. This study establishes design principles for resilient jamming architectures and supports enhanced survivability against radars employing pulse compression and CFAR detection. Moreover, the concepts proposed in this study have the potential for extension to emerging radar waveforms.
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A novel composite (nZVI/HNTs) was prepared via incorporating nano zero-valent iron (nZVI) on halloysite nanotubes (HNTs) for degrading tetracycline hydrochloride (TCH) with existence of persulfate (PS). The adsorption process of nZVI/HNTs to TCH conformed to the Freundlich isotherm model and pseudo-second-order kinetic model, and its maximum adsorption capacity was 76.62 mg·g-1. Furthermore, the nZVI/HNTs + PS system exhibited satisfactory degradation efficiency (84.21%) for TCH, and stable nZVI/HNTs (Fe leaching < 0.001 mg·L-1) could be reused. When nZVI/HNTs dosage, PS dosage and temperature increased, TCH degradation could be enhanced. After four cycling, nZVI/HNTs + PS system had still 65.8% degradation for TCH. The quenching tests and EPR analysis evidenced that SO4â¢- was predominant instead of â¢OH in such system. Three possible pathways of TCH degradation were provided through the liquid chromatograph-mass spectrometer (LC-MS) determination. Meanwhile, the biological toxicity prediction analysis indicated that the nZVI/HNTs + PS system would be an environment friendly treatment method toward TCH pollution.
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Nanotubos , Contaminantes Químicos del Agua , Tetraciclina/análisis , Arcilla , Hierro/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Introduction: Although there is extended research on the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in adult cancer patients (ACP), the immunogenicity to the variants of concern (VOCs) in childhood cancer patients (CCP) and safety profiles are now little known. Methods: A prospective, multi-center cohort study was performed by recruiting children with a solid cancer diagnosis and childhood healthy control (CHC) to receive standard two-dose SARS-CoV-2 vaccines. An independent ACP group was included to match CCP in treatment history. Humoral response to six variants was performed and adverse events were followed up 3 months after vaccination. Responses to variants were compared with ACP and CHC by means of propensity score-matched (PSM) analysis. Results: The analysis included 111 CCP (27.2%, median age of 8, quartile 5.5-15 years), 134 CHC (32.8%), and 163 ACP (40.0%), for a total 408 patients. Pathology included carcinoma, neural tumors, sarcoma, and germ cell tumors. Median chemotherapy time was 7 (quartile, 5-11) months. In PSM sample pairs, the humoral response of CCP against variants was significantly decreased, and serology titers (281.8 ± 315.5 U/ml) were reduced, as compared to ACP (p< 0.01 for the rate of neutralization rate against each variant) and CHC (p< 0.01 for the rate of neutralization against each variant) groups. Chemotherapy time and age (Pearson r ≥ 0.8 for all variants) were associated with the humoral response against VOCs of the CHC group. In the CCP group, less than grade II adverse events were observed, including 32 patients with local reactions, and 29 patients had systemic adverse events, including fever (n = 9), rash (n = 20), headache (n = 3), fatigue (n = 11), and myalgia (n = 15). All reactions were well-managed medically. Conclusions: The humoral response against VOCs after the CoronaVac vaccination in CCP was moderately impaired although the vaccine was safe. Age and chemotherapy time seem to be the primary reason for poor response and low serology levels.
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COVID-19 , Sarcoma , Humanos , Adulto , Niño , Preescolar , Adolescente , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Estudios de Cohortes , Estudios Prospectivos , COVID-19/prevención & control , VacunaciónRESUMEN
Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan-Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were -4.26 ± 8.54 (3rd month), -4.72 ± 11.83 (6th month), -6.16 ± 15.41 (9th month), -6.07 ± 15.71 (12th month), and -7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project.
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Inflammasomes are cytosolic sensors of pathogens. Their activation can lead to the induction of caspase-1-mediated inflammatory responses and the release of several proinflammatory cytokines, including IL-1ß. There is a complex relationship between viral infection and the nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome. The activation of the NLRP3 inflammasome is essential for antiviral immunity, while excessive NLRP3 inflammasome activation may lead to excessive inflammation and pathological damage. Meanwhile, viruses have evolved strategies to suppress the activation of inflammasome signaling pathways, thus escaping immune responses. In this study, we investigated the inhibitory effect of coxsackievirus B3 (CVB3), a positive single-strand RNA virus, on the activation of the NLRP3 inflammasome in macrophages. CVB3-infected mice had significantly lower production of IL-1ß and a lower level of NLRP3 in the small intestine after LPS stimulation. Furthermore, we found that CVB3 infection inhibited NLRP3 inflammasome activation and IL-1ß production in macrophages by suppressing the NF-κB signaling pathway and ROS production. Additionally, CVB3 infection increased the susceptibility of mice to Escherichia coli infection by decreasing IL-1ß production. Collectively, our study revealed a novel mechanism of NLRP3 inflammasome activation by suppressing the NF-κB pathway and ROS production in LPS-induced macrophages. Our findings may provide new ideas for antiviral treatment and drug development for CVB3 infection.
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Inflamasomas , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Antivirales/farmacologíaRESUMEN
Context: Severe acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk. Objectives: We primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk. Methods: The retrospective, multi-center study recruited patients with HT receiving COVID-19-inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score-matched comparisons between the vaccine and control groups were carried out to investigate the difference. Results: Final analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan-Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes. Conclusion: COVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.
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COVID-19 , Enfermedad de Hashimoto , Humanos , Vacunas contra la COVID-19/efectos adversos , Estudios Retrospectivos , COVID-19/prevención & control , COVID-19/complicaciones , Tirotropina , AnticuerposRESUMEN
Global warming is a life-threatening risk to mankind and its survival; to combat this risk, the considerable contribution of renewable energy cannot be overlooked for sustainable growth globally. The aim of this paper is to scrutinize the threshold level and asymmetric connection among renewable energy consumption, foreign direct investment, financial inclusion, and agricultural productivity in dissimilar regimes of the different income levels of 123 countries from 1995 to 2019 by applying an advance technique PSTR (panel smooth transition regression) model. The PSTR model results imply that the connection between renewable energy consumption and agricultural productivity at all the estimates is non-linear. Moreover, in all countries, there is a positive and significant connection among renewable energy consumption, foreign direct investment, financial inclusion, and agricultural productivity in both low and high regimes, except the carbon emission, which has a negative and significant impact on agricultural productivity. Based on the results of this study, the recommendations are as follows: (i) to increase renewable energy consumption, efficient-energy resources should be used by farmers for the agricultural process; (ii) the dependence on non-renewable energy resources should be minimized and shifted towards natural and renewable resources.