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BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.
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Asma , Plaquetas , Nanopartículas , Polifenóis , Chá , Animais , Camundongos , Polifenóis/administração & dosagem , Polifenóis/farmacologia , Asma/tratamento farmacológico , Asma/metabolismo , Nanopartículas/administração & dosagem , Chá/química , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Administração por Inalação , Humanos , Camundongos Endogâmicos BALB C , Feminino , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Sepsis is a critical condition with a significant risk of mortality. Advanced age is one factor in increasing mortality in intensive care. OBJECTIVES: The aim of this study is to investigate the association between mean heart rate (MHR) and 30-day mortality among older patients with sepsis in the intensive care unit (ICU). METHODS: All older patients (age 65 or older) with sepsis for first time in ICU admission in Medical Information Mart for Intensive Care-IV (MIMIC-IV) were included in this retrospective study. The effect of MHR within 24 h of ICU admission on 30-day mortality was assessed according to multivariable Cox regression models, restricted cubic splines and two-piecewise Cox regression models. RESULTS: The total number of participants was 6598 (mean heart rate, 83.8±14.3 bpm). A total of 1295 (19.6%) patients died within 30 days after ICU admission. MHR within 24 h of admission was associated with 30-day mortality (J-shaped association) in older patients with sepsis in the ICU, with an inflection point at about 74 bpm and a minimal risk observed at 73 to 82 bpm of MHR. CONCLUSIONS: In this retrospective cohort study, there was a J-shaped association between MHR and 30-day mortality in older patients with sepsis admitted to the ICU and a minimal risk observed at 73 to 82 bpm of MHR. If further confirmed, this association may provide a theoretical basis for formulating the target strategy of heart rate therapy for these patients.
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The construction of doped molecular clusters is an intriguing way to perform bimetallic doping for electrocatalysts. However, efficiently harnessing the benefits of a doping strategy and alloy engineering to create a nanostructure for electrocatalytic application at the molecular level has consistently posed a challenge. Here we propose an in situ reconstruction strategy aimed at producing an alloy nanostructure through a pyrolysis process, originating from bowknot-like heterometallic clusters. The Schiff base, denoted as ligand L1 (o-vanillin ethylenediamine), was introduced as a precursor to coordinate Fe and Co metals, thereby yielding a heteronuclear metal cluster [(FeCo)(L1)2O]CH3CN. Subsequently, a comprehensive investigation of the in situ reconstruction process [(FeCo)(L1)2O](CH3CN) â [(FeCo)(L1)2O] â [M-O-M/M-O] [CH3+/CH3O+/H2CâN/C2H5+/C4H4+] â [FeCo/Fe3O4/Fe2O3/Co3O4][carbon layer] led to the formation of MOx/CoFe@NC-700 during the pyrolysis. This process reveals that the metals Fe and Co in the clusters undergo partly in situ evolution into FeCo alloys, resulting in the successful preparation of MOx/CoFe@NC (M = Fe, Co) nanomaterials that leverage the advantages of both doping strategies and alloy engineering. The synergistic interaction between alloy particles and metal oxides establishes active sites that contribute to the excellent oxygen evolution (OER) and hydrogen evolution (HER) catalytic behaviors. Notably, these materials exhibit outstanding OER and HER properties under alkaline conditions, with overpotentials of 191 and 88 mV for OER and HER, respectively, at 10 mA cm-2. Investigation of the in situ conversion of Schiff base bimetal clusters into alloy materials through pyrolysis offers a novel strategy for advancing electrocatalytic applications.
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Energy-intensive load benefits from low electricity tariff and carbon emission, since they occupy certain amounts in the total cost of the product. This paper considers energy-intensive load participation in the electricity as well as carbon trading to reduce the cost. Firstly, an electricity-carbon model is established based on the correlation value method to calculate the carbon emissions of energy-intensive load based on their electricity consumption to realize the carbon amount. Afterwards, the baseline method is used to allocate free carbon emission quotas to energy-intensive load and a reward-penalty carbon trading price mechanism considering offset is proposed. Next, the objective function to achieve maximum benefits, and to reduce output fluctuation, and to improve new energy accommodation is proposed. The case studies show that, by comparing multi-objective function optimization, the optimization target proposed in this paper can effectively reduce wind power output fluctuations and improve wind power accommodation. Through the total participation in carbon trading and electricity market income, multi-objective optimization can increase the system income while ensuring that energy-intensive load meets production requirements under the premise of reducing carbon emissions, verifying the effectiveness of the low-carbon optimal operation model proposed in this paper.
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PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.
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DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Nivolumabe , Carga Viral , Humanos , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , DNA Viral/sangue , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/sangue , Estudos Retrospectivos , Adulto , Recidiva Local de Neoplasia/virologia , Nivolumabe/uso terapêutico , Genoma Viral , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. METHODS AND STUDY DESIGN: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.
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Diabetes Gestacional , Dieta , Inflamação , Sobrepeso , Humanos , Diabetes Gestacional/epidemiologia , Feminino , Gravidez , Dieta/métodos , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. METHODS: This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). FINDINGS: Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. INTERPRETATION: V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. FUNDING: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).
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The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60â, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2-) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2- were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09-0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %-22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.
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Psoriasis and atopic dermatitis (AD) are both chronic inflammatory skin diseases, which are common and difficult to cure. Currently, the emerging biologics have demonstrated outstanding efficacy, but not all patients are able to benefit from them, and traditional systemic treatments come with many severe side effects. The emergence of immune checkpoints brings new hope to solve this problem. Immune checkpoints regulate T cell activation. Upon damage to the co-inhibitory molecules, the inhibition on T cells is removed, leading to the excessive activation of T cells. In this review, we delineate and highlight the expression and function of immune checkpoint molecules (CTLA-4, PD-1, TIM-3, TIGIT, VISTA, LAG-3, OX40, GITR) in psoriasis and AD. We provide preclinical and clinical studies supporting a potential therapeutic approach of targeting these checkpoints for inflammatory skin diseases. Moreover, the complexity of immune checkpoints and safety of clinical application are discussed.
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Dermatite Atópica , Psoríase , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/tratamento farmacológico , Psoríase/imunologia , Psoríase/tratamento farmacológico , Animais , Proteínas de Checkpoint Imunológico/metabolismo , Proteínas de Checkpoint Imunológico/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos T/imunologiaRESUMO
Ultraviolet B (UVB) radiation accelerates the aging process of skin cells by triggering oxidative stress and inflammatory responses. The aim of this study was to investigate the mechanism of action of sRNAs and protein molecules in the regenerative extracellular vesicles of Lactobacillus plantarum against the UVB-induced photoaging process of human keratinocytes. The extracellular vesicles regenerated by Lactobacillus plantarum were isolated and purified to identify sRNAs and protein components. Human keratinocytes were treated with UVB radiation to simulate the photoaging model. The effects of different concentrations of vesicle extract on cell survival rate, oxidative stress index and inflammatory marker expression were evaluated in control group and treatment group. The results showed that the regenerated extracellular vesicles of L. plantarum significantly improved the survival rate of keratinocytes after UVB radiation, and delayed the aging process of skin cells by reducing oxidative stress and inhibiting inflammatory response.
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Vesículas Extracelulares , Queratinócitos , Lactobacillus plantarum , Envelhecimento da Pele , Raios Ultravioleta , Lactobacillus plantarum/química , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Vesículas Extracelulares/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pequeno RNA não TraduzidoRESUMO
Herein, two poly(3-aminocarbazole) derivatives containing imidazole N-type acceptor were synthesized and reported, which are named PCPI and PCBI respectively. The fluorescence spectrum shows that PCPI (Em = 498 nm) and PCBI (Em = 398 nm) both have a strong fluorescence emission. It is worth noting that PCPI has a larger stokes shift of 153 nm, which is beneficial for improving the sensitivity of the sensor and enhancing its anti-interference ability. As expected, our experimental results indicate that both PCPI and PCBI can cause a specific response of "fluorescence OFF" to Hg2+ compared with other ions. And PCPI and PCBI both have excellent detection capabilities for Hg2+, with detection limits of 69.8 nM and 11.4 nM respectively. Moreover, PCBI exhibits excellent absorption of Hg2+ with a maximum absorption capacity of 477.8 mg/g at 20 °C. It indicates that PCBI can be used as a functional material for the detection and removal of Hg2+ in water.
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Carbazóis , Mercúrio , Poluentes Químicos da Água , Mercúrio/análise , Mercúrio/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Adsorção , Carbazóis/química , Água/química , Espectrometria de Fluorescência , Polímeros/química , Limite de DetecçãoRESUMO
Herein, hydrothermal method was used to prepare a series of multi-color polythiophene modified carbon quantum dots. Under UV excitation, fluorescence their maximum emission wavelengths appear at 612 nm, 570 nm, and 540 nm respectively. The prepared CD-BTH and CD-BN can have specific detection of Au3+ and Hg2+ through fluorescence quenching effect. The detection limits for Au3+ are 3 nM and 5.4 nM respectively, and for Hg2+ are 23 nM and 90 nM respectively. CD-KN detects Au3+ specifically through fluorescence resonance, with a detection limit of 33 nM. Under the interference of other metal ions, three types of polythiophene modified quantum carbon dots exhibit excellent selectivity for the responsive ions. Meanwhile, this article also elucidates the law that as the electron withdrawing ability of the side chains of polythiophene derivatives increasing, the fluorescence emission peaks of the prepared polythiophene modified carbon dots shifts red and the fluorescence quantum yield is higher.
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Interactions between glycan-binding proteins (GBPs) and glycosphingolipids (GSLs) present in cell membranes are implicated in a wide range of biological processes. However, studying GSL binding is hindered by the paucity of purified GSLs and the weak affinities typical of monovalent GBP-GSL interactions. Native mass spectrometry (nMS) performed using soluble model membranes is a promising approach for the discovery of GBP ligands, but the detection of weak interactions remains challenging. The present work introduces MEmbrane ANchor-assisted nMS (MEAN-nMS) for the detection of low-affinity GBP-GSL complexes. The assay utilizes a membrane anchor, produced by covalent cross-linking of the GBP and a lipid in the membrane, to localize the GBP on the surface and promote GSL binding. Ligands are identified by nMS detection of intact GBP-GSL complexes (MEAN-nMS) or using a catch-and-release (CaR) strategy, wherein GSLs are released from GBP-GSL complexes upon collisional activation and detected (MEAN-CaR-nMS). To establish reliability, a library of purified gangliosides incorporated into nanodiscs was screened against human immune lectins, and the results compared with affinities of the corresponding ganglioside oligosaccharides. Without a membrane anchor, nMS analysis yielded predominantly false negatives. In contrast, all ligands were identified by MEAN-(CaR)-nMS, with no false positives. To highlight the potential of MEAN-CaR-nMS for ligand discovery, a natural library of GSLs was incorporated into nanodiscs and screened against human and viral proteins to uncover elusive ligands. Finally, nMS-based detection of GSL ligands directly from cells is demonstrated. This breakthrough paves the way for shotgun glycomics screening using intact cells.
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Glicoesfingolipídeos , Espectrometria de Massas , Glicoesfingolipídeos/química , Glicoesfingolipídeos/metabolismo , Espectrometria de Massas/métodos , Humanos , Membrana Celular/metabolismo , Membrana Celular/química , Ligantes , Ligação ProteicaRESUMO
BACKGROUND: Pneumococcal diseases (PD) cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from pneumococcal serotypes responsible for the majority of residual PD. This phase 3 study evaluated safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-experienced adults ≥50 years. METHODS: A total of 717 adults were enrolled to receive a single dose of pneumococcal vaccine as follows: Cohort 1 (n=350) previously received PPSV23 and were randomized 2:1 to receive V116 or PCV15, respectively; Cohort 2 (n=261) previously received PCV13 and were randomized 2:1 to receive V116 or PPSV23, respectively; Cohort 3 (n=106) previously received PPSV23+PCV13, PCV13+PPSV23, PCV15+PPSV23, or PCV15 and all received open-label V116. Immunogenicity was evaluated 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) for all V116 serotypes. Safety was evaluated as the proportion of participants with adverse events (AEs). RESULTS: V116 was immunogenic across all 3 cohorts as assessed by serotype-specific OPA GMTs and IgG GMCs postvaccination for all 21 serotypes. V116 elicited comparable immune responses to serotypes shared with PCV15 (Cohort 1) or PPSV23 (Cohort 2), and higher immune responses to serotypes unique to V116. The proportions of participants with solicited AEs were generally comparable across cohorts. CONCLUSIONS: V116 is well tolerated with a safety profile comparable to currently licensed pneumococcal vaccines and generates IgG and functional immune responses to all V116 serotypes, regardless of prior pneumococcal vaccine received.
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Low-energy visible-light-activated carbon dots (CDs)-based afterglow materials are difficult to realize due to the inherent aromatic carbon with high-energy absorption and the lack of effective regulation. Here, a new strategy for visible-light-activated CDs is proposed by combining dual-confinement and surface-ionization, which employs NaOH for additional confinement and surface ionization of CDs in a single boric acid (BA) matrix. The comparison experiments show that: i) shifting the excitation from UV-light to vis-light is realized by enhancing the low-energy surface states nâπ* transition of the CDs by surface ionization of NaOH. ii) CDs are additionally protected by a more stable NaâO ionic bond after NaOH confinement, resulting in a brighter afterglow. iii) the energy gap (ΔEST) between the lowest singlet and triplet states is gradually shortened as increasing NaOH content, facilitating intersystem crossing, prolonging the lifetime of triplet excitons and efficiency. Further, vis-light-excited colorful afterglow powders are fabricated based on Förster Resonant Energy Transfer by combining the fluorescent dye 5-carboxytetramethylrhodamine. Finally, advanced white-light-activated time-resolved anti-counterfeiting and intelligent traffic flashing signs are realized. The work may shed new light on the design of low-energy-activated afterglow materials and broaden the application scenarios in the daily lives of human society.