ABSTRACT
Cathepsin G (CTSG) plays an important role in the regulation of immune processes. Accumulated studies show that CTSG is involved in the onset and development of type 1 diabetes mellitus (T1DM). As the genetic background of T1DM varies widely among populations, we aimed to study the relationship between genetic polymorphisms in CTSG and T1DM susceptibility in Chinese populations. A total of 141 patients with T1DM and 200 healthy controls were enrolled in the study. Serum CTSG expression was detected using enzyme-linked immunosorbent assay (ELISA). Genotyping of two selected single nucleotide polymorphisms (SNPs) (rs2236742 and rs2070697) of CTSG was performed using PCR and Sanger sequencing. CTSG expression in patients with T1DM was significantly higher than in the control group. Alleles C and T of CTSG SNP rs2236742 were increased in T1DM. No significant associations were found for the SNP rs2070697. Our results indicate that the CTSG rs2236742 allele (C/T) is associated with T1DM in Chinese children and may serve as a new biomarker for predicting T1DM susceptibility.
Subject(s)
Alleles , Asian People , Diabetes Mellitus, Type 1 , Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , Humans , Diabetes Mellitus, Type 1/genetics , Female , Male , Child , Case-Control Studies , Asian People/genetics , China/epidemiology , Child, Preschool , Gene Frequency , Enzyme-Linked Immunosorbent Assay , Adolescent , Polymerase Chain Reaction , Biomarkers/blood , East Asian PeopleABSTRACT
Persistent infection with high-risk human papillomavirus (HPV) types can lead to the development of cancer in HPV-infected tissues, including the cervix, oropharynx, anus, penis, vagina, and vulva. While current HPV vaccines cover approximately 90 % of cervical cancers, nearly 10 % of cases associated with HPV types not included in the vaccines remain unaddressed, notably HPV59. This study describes the development of a chimeric virus-like particle (VLP) targeting HPV18/45/59, proposed as a vaccine candidate for high-risk HPV type (HPV59) currently lacking commercial vaccines. Given that the majority of neutralizing antibody epitopes are located on the surface loops, we engineered a strategic swap of these loops between the closely related HPV18 and HPV45. This methodology was then extended to incorporate surface loops of HPV59, resulting in the lead candidate construct of the H18-45BCEF-59HI chimeric VLP with two surface loops swapping from HPV45 to HPV18. Characterization confirmed that H18-45BCEF-59HI closely resembled the wild-type (WT) backbone types in particle size and morphology, as verified by Transmission Electron Microscopy (TEM), High-Performance Size-Exclusion Chromatography (HPSEC), and Analytical Ultracentrifugation (AUC), and demonstrated similar thermal stability as evidenced by Differential Scanning Calorimetry (DSC). Immunization studies in mice with the chimeric VLPs assessed their immunogenicity, revealing that the H18-45EF-59HI chimeric VLP exhibited optimal cross-neutralization. Additionally, when produced in a Good Manufacturing Practice (GMP)-like facility, the H18-45BCEF-59HI VLP was selected as a promising vaccine candidate for the prevention of HPV18/45/59 infection. This study not only offers a potential solution to the current vaccination gap but also provides a foundational approach for the design of vaccines targeting viruses with multiple subtypes or variants.
ABSTRACT
Ascorbic acid (AsA) is an indicator of the nutritional value of freshly cut kiwifruit during storage at 4â, and its degradation can be inhibited after ozone treatment (1 mg/L, 10 min). The aim of this study was to elucidate the regulatory mechanism affecting AsA metabolism in fresh-cut kiwifruit after ozone treatment. In this study, ozone treatment not only prevented the decrease in AsA/dehydroascorbic acid and delayed the accumulation of total soluble solids/titratable acidity, but also altered phytohormone levels differently. Transcriptomic profiling combined with cis-acting element and correlation analysis were performed to reveal that abscisic acid and salicylic acid synergistically delay AsA degradation under ozone-treatment conditions. Actinidia03760, encoding ascorbate peroxidase, could be specifically recognized by the bZIP transcription factor and is considered a key candidate gene for further research. Collectively, ozone treatment is a promising method for preserving AsA content and improving the nutrition of fresh-cut kiwifruit.
Subject(s)
Actinidia , Ascorbic Acid , Fruit , Gene Expression Profiling , Ozone , Plant Growth Regulators , Signal Transduction , Actinidia/genetics , Actinidia/chemistry , Actinidia/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Fruit/metabolism , Fruit/chemistry , Fruit/drug effects , Signal Transduction/drug effects , Gene Expression Regulation, Plant/drug effects , Transcriptome , Salicylic Acid , Abscisic Acid/metabolismABSTRACT
Aggression is one of the public social issues affecting campus harmony and stability, and social exclusion is an important interpersonal contextual factor among many factors affecting aggression. However, studies examining the influence of social exclusion on aggression and its mediating mechanism are not systematic enough. Based on the general aggression model (GAM), we intend to explore the role of hostile attribution bias (HAB) in both trait and state levels of social exclusion, which leads to aggression through a combination of questionnaire and experimental methods. Study 1 surveyed 388 current high school students (Mage = 16.09, SD = 1.01) and found that HAB mediates the relationship between long-term social exclusion (trait level) and aggression tendency. Study 2 experimented with 181 high school students (Mage = 16.95, SD = 1.13) to examine whether short-term social exclusion (state level) after initiating the Cyberball paradigm could still influence aggressive behavior through the mediating role of HAB. Results found that the mediating role of HAB still holds. The findings of the study further enrich the GAM and have important implications for a more targeted approach to aggression prevention and intervention.
Subject(s)
Aggression , Hostility , Psychological Distance , Humans , Aggression/psychology , Male , Female , Adolescent , Students/psychology , Social Perception , Adolescent Behavior/psychologyABSTRACT
In this paper, a compact silicon-based photonic microwave frequency downconverter with broadband operation capability and continuous phase shift tunability is proposed and experimentally demonstrated. The photonic converter mainly comprises two micro-ring modulators (MRMs) connected in parallel and a cascaded resonator-based optical bandpass filter (OBPF) whose size is merely 200 × 700â µm2. In the proposed device, a radio frequency (RF) signal and a local oscillator (LO) signal drive the two MRMs for realizing the electro-optic conversion. The OBPF is utilized for selecting the first-order sidebands of both RF and LO signals. By manipulating the phase difference between the RF and LO optical sidebands through thermal-optic effect, the phase of the obtained intermediate frequency (IF) signal from a photodiode can be tuned continuously. Experimental results demonstrate a 137° phase shift while the RF signals of 20 and 40â GHz are downconverted to an IF signal of 0.4â GHz, which indicates the photonic microwave downconverter can be used in the Ka-band phased-array receiver.
ABSTRACT
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a common phenotype in children with myelin oligodendrocyte glycoprotein IgG (MOG-IgG)-associated disease. We aimed to identify novel genetic variants that distinguish children with MOG-IgG-positive ADEM (MOG-IgG+ ADEM) from children with MOG-IgG-negative ADEM (MOG-IgG- ADEM) using whole exome sequencing (WES) analysis. METHODS: We conducted a two-stage study design. First, we performed WES on five patients with MOG-IgG+ ADEM and five patients with MOG-IgG- ADEM. Following bioinformatics analysis, the candidate variant list was constructed. Second, 29 children with MOG-IgG+ ADEM and 27 children with MOG-IgG- ADEM, together with discovery cohort, were genotyped to identify the novel variants. RESULTS: WES resulted in 33,999 variants, and 5388 nonsynonymous variants were selected for downstream analysis. In total, 118 protein-affecting variants that were significantly different between the two groups were identified. Together with the five variants extracted from the literature, 49 variants were selected as the candidate variant list for genotyping in the replication cohort. Finally, we identified three variants: rs11171951 in NACα, rs231775 in CTLA4, and rs11171951 in GOLGA5, which were significantly different between MOG-IgG+ ADEM and MOG-IgG- ADEM. Only rs12440118 in NACα remained significant after Bonferroni correction for multiple testing (Padj < 0.001). CONCLUSIONS: We identified strong associations between NACα, CTLA4, and GOLGA5 variants and MOG-IgG+ ADEM in a Han Chinese population of Northern China, which may present novel genetic risk factor distinguishing patients with MOG-IgG+ ADEM from those with MOG-IgG- ADEM.
Subject(s)
Encephalomyelitis, Acute Disseminated , Immunoglobulin G , Myelin-Oligodendrocyte Glycoprotein , Humans , Myelin-Oligodendrocyte Glycoprotein/immunology , Myelin-Oligodendrocyte Glycoprotein/genetics , Encephalomyelitis, Acute Disseminated/genetics , Child , Male , Female , China , Child, Preschool , Immunoglobulin G/blood , Exome Sequencing , Genetic Variation , Adolescent , Infant , Autoantibodies/bloodABSTRACT
Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.
Subject(s)
Brain , Child Development , Child , Child, Preschool , Humans , Brain/growth & development , Brain/diagnostic imaging , China , Cognition , Databases, Factual , NeuroimagingABSTRACT
Emotional recognition is a pivotal research domain in computer and cognitive science. Recent advancements have led to various emotion recognition methods, leveraging data from diverse sources like speech, facial expressions, electroencephalogram (EEG), electrocardiogram, and eye tracking (ET). This article introduces a novel emotion recognition framework, primarily targeting the analysis of users' psychological reactions and stimuli. It is important to note that the stimuli eliciting emotional responses are as critical as the responses themselves. Hence, our approach synergizes stimulus data with physical and physiological signals, pioneering a multimodal method for emotional cognition. Our proposed framework unites stimulus source data with physiological signals, aiming to enhance the accuracy and robustness of emotion recognition through data integration. We initiated an emotional cognition experiment to gather EEG and ET data alongside recording emotional responses. Building on this, we developed the Emotion-Multimodal Fusion Neural Network (E-MFNN), optimized for multimodal data fusion to process both stimulus and physiological data. We conducted extensive comparisons between our framework's outcomes and those from existing models, also assessing various algorithmic approaches within our framework. This comparison underscores our framework's efficacy in multimodal emotion recognition. The source code is publicly available at https://figshare.com/s/8833d837871c78542b29.
ABSTRACT
Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T10 on the surface of cross-linked lipoic acid vesicles (T10@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe2+ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe2+ to further boost the ferroptosis. The results disclosed that T10@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.
Subject(s)
Ferroptosis , Nanoparticles , Neoplasms , Mice , Animals , Transferrin/metabolism , Mice, Nude , Iron/metabolism , Ferritins , Nanoparticles/chemistryABSTRACT
Many organic contaminated sites require on-site remediation; excavation remediation processes can release many volatile organic compounds (VOCs) which are key atmospheric pollutants. It is therefore important to rapidly identify VOCs during excavation and map their risk areas for human health protection. In this study, we developed a rapid analysis and assessment method, aiming to and reveal the real-time distribution of VOCs, evaluate their human health risks by quantitative models, and design appropriate control measures. Through on-site diagonal distribution sampling and analysis, VOCs concentration showed a decreasing trend within 5 m from the excavation point and then increased after 5 m with the increase in distance from the excavation point (p < 0.05). The concentrations of VOCs near the dominant wind direction were higher than the concentrations of surrounding pollutants. In contrast with conventional solid-phase adsorption (SPA) and thermal desorption gas chromatography-mass spectrometry (TD-GC/MS) methods for determining the composition and concentration of VOCs, the rapid measurement of VOCs by photo-ionization detector (PID) fitted well with the chemical analysis and modeling assessment of cancer/non-cancer risk. The targeting area was assessed as mild-risk (PID < 10 ppm), moderate-risk (PID from 10 to 40 ppm), and heavy-risk (PID > 40 ppm) areas. Similarly, the human health risks also decreased gradually with the distance from the excavation point, with the main risk area located in the dominant wind direction. The results of rapid PID assessment were comparable to conventional risk evaluation, demonstrating its feasibility in rapidly identifying VOCs releases and assessing the human health risks. This study also suggested appropriate control measures that are important guidance for personal protection during the remediation excavation process.
Subject(s)
Air Pollutants , Environmental Pollutants , Volatile Organic Compounds , Humans , Air Pollutants/analysis , Environmental Monitoring/methods , Volatile Organic Compounds/analysis , Gas Chromatography-Mass Spectrometry , Environmental Pollutants/analysisABSTRACT
Introduction: Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Methods: Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. Results: PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. Conclusion: PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.
Subject(s)
Cell-Penetrating Peptides , Choroidal Neovascularization , Macular Degeneration , Mice , Animals , Humans , Liposomes/therapeutic use , Angiogenesis Inhibitors/pharmacology , Hyaluronic Acid , Vascular Endothelial Growth Factor A , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/metabolism , Macular Degeneration/drug therapy , Ophthalmic Solutions/therapeutic use , Intravitreal InjectionsABSTRACT
Coal mining is one of the human activities that has the greatest impact on the global carbon (C) cycle and biodiversity. Biochar and plant growth-promoting bacteria (PGPB) have been both used to improve coal mining degraded soils; however, it is uncertain whether the effects of biochar application on soil respiration and microbial communities are influenced by the presence or absence of PGPB and soil nitrogen (N) level in coal mining degraded soils. A pot experiment was carried out to examine whether the effects of biochar addition (0, 1, 2 and 4% of soil mass) on soil properties, soil respiration, maize growth, and microbial communities were altered by the presence or absence of PGPB (i.e. Sphingobium yanoikuyae BJ1) (0, 200 mL suspension (2 × 106 colony forming unit (CFU) mL-1)) and two soil N levels (N0 and N1 at 0 and 0.2 g kg-1 urea- N, respectively). The results showed the presence of BJ1 enhanced the maize biomass relative to the absence of BJ1, particularly in N1 soils, which was related to the discovery of Lysobacter and Nocardioides that favor plant growth in N1 soils. This indicates a conversion in soil microbial communities to beneficial ones. The application of biochar at a rate of 1% decreased the cumulative CO2 regardless of the presence or absence of BJ1; BJ1 increased the ß-glucosidase (BG) activities, and BG activities were also positively correlated with RB41 strain with high C turnover in N1 soils, which indicates that the presence of BJ1 improves the C utilization rates of RB41, decreasing soil C mineralization. Our results highlight that biochar addition provided environmental benefits in degraded coal mining soils, and the direction and magnitude of these effects are highly dependent on the presence of PGPB and the soil N level.
Subject(s)
Coal Mining , Zea mays , Humans , Carbon Dioxide/metabolism , Soil , Soil Microbiology , Charcoal/metabolism , BacteriaABSTRACT
Heat stress (HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides (SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde (MDA) content of thigh muscle, whereas decreased the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 (Nrf2), selenoprotein S (SELENOS), solute carrier family 7 member 11 (SLC7A11), GPX4, and ferroportin 1 (Fpn1) of thigh muscle (P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase (GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 (FTH1), and Fpn1 of thigh muscle in broilers under HS (P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis (P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.
Subject(s)
Ferroptosis , Selenium , Animals , Antioxidants/metabolism , Selenium/metabolism , Chickens/physiology , Thigh , Dietary Supplements/analysis , Muscle, Skeletal , Heat-Shock Response , Superoxide Dismutase/metabolism , Meat/analysis , RNA, Messenger/metabolism , Animal Feed/analysisABSTRACT
Human behavior often aligns with fairness norms, either voluntarily or under external pressure, like sanctions. Prior research has identified distinct neural activation patterns associated with voluntary and sanction-based compliance or non-compliance with fairness norms. However, an investigation gap exists into potential neural connectivity patterns and sex-based differences. To address this, we conducted a study using a monetary allocation game and functional magnetic resonance imaging to examine how neural activity and connectivity differ between sexes across three norm compliance conditions: voluntary, sanction-based, and voluntary post-sanctions. Fifty-five adults (27 females) participated, revealing that punishment influenced decisions, leading to strategic calculations and reduced generosity in voluntary compliance post-sanctions. Moreover, there were sex-based differences in neural activation and connectivity across the different compliance conditions. Specifically, the connectivity between the right dorsolateral prefrontal cortex and right dorsal anterior insular appeared to mediate intuitive preferences, with variations across norm compliance conditions and sexes. These findings imply potential sex-based differences in intuitive motivation for diverse norm compliance conditions. Our insights contribute to a better understanding of the neural pathways involved in fairness norm compliance and clarify sex-based differences, offering implications for future investigations into psychiatric and neurological disorders characterized by atypical socialization and mentalizing.
Subject(s)
Magnetic Resonance Imaging , Social Behavior , Adult , Female , Humans , Sex Characteristics , Motivation , Insular CortexABSTRACT
Schizophrenia (SCZ) is a heterogeneous psychiatric disorder marked by impaired thinking, emotions, and behaviors. Studies have suggested a strong connection between SCZ and Alzheimer's disease (AD), however, controversies exist and the underlying mechanisms linking these two disorders remain largely unknown. Therefore, systematic studies of SCZ- and AD-related genes will provide valuable insights into the molecular features of these two diseases and their comorbidities. In this study, we obtained 331 SCZ-related genes, 650 AD-related genes, 65 shared genes between SCZ and AD. Enrichment analysis shown that these 65 shared genes were mainly involved in cognition, neural development, synaptic transmission, drug reactions, metabolic processes and immune related processes, suggesting a complex mechanism for the co-existence of SCZ and AD. In addition, we performed pathway enrichment analysis and found a total of 57 common pathways between SCZ and AD, which could be largely grouped into three modules: immune module, neurodevelopment module and cancer module. We eventually identified the potential disease-related genes whose interactions provide clues to the overlapping symptoms between SCZ and AD.
Subject(s)
Alzheimer Disease , Schizophrenia , Humans , Schizophrenia/genetics , Schizophrenia/metabolism , Alzheimer Disease/genetics , Synaptic Transmission , ComorbidityABSTRACT
In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.
Subject(s)
Papillomavirus Vaccines , Animals , Mice , Broadly Neutralizing Antibodies , Capsid Proteins/genetics , Antibodies, Viral , Human papillomavirus 6 , Immunization , Amino AcidsABSTRACT
Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, ß-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers.
ABSTRACT
BACKGROUND: Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood-brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33. METHODS: Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated. RESULTS: We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke. CONCLUSION: Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Mice , Animals , Ischemic Stroke/pathology , Blood-Brain Barrier , Interleukin-33/pharmacology , Lipogenesis , Mice, Inbred C57BL , Stroke/pathology , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , RNA, Small Interfering/metabolism , Atrophy/pathology , Brain Ischemia/metabolismABSTRACT
INTRODUCTION: The objective of this research was to investigate the effect of person-job fit on occupational commitment among Chinese kindergarten teachers, and to identify strategies for improving the occupational commitment of this professional group. METHODS: A survey was conducted among kindergarten teachers utilizing the Occupational Commitment Scale, Person-job Fit Scale, Occupational Well-being Scale, and Perceived Organizational Support Scale, resulting in the acquisition of 1539 valid data. RESULTS: A significant positive correlation was observed between person-job fit and occupational commitment, with occupational well-being serving as a partial mediator in this association. Additionally, the direct effect of person-job fit on occupational commitment was moderated by perceived organizational support. Specifically, a significant positive correlation between person-job fit and occupational commitment was evident when the scores of perceived organizational support were below 0.21, whereas a significant negative correlation was observed when the scores of perceived organizational support were above 1.67. CONCLUSIONS: In order to enhance the degree of occupational commitment among kindergarten teachers, it is imperative to pay attention to their person-job fit, perceived organizational support, and occupational well-being.