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1.
N Engl J Med ; 388(7): 621-634, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36791162

RESUMO

BACKGROUND: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. METHODS: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-µg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-µg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 µg of BNT162b2 in the pivotal trial. RESULTS: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-µg dose) and 48 children 2 to 4 years of age (3-µg or 10-µg dose). The 3-µg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). CONCLUSIONS: A three-dose primary series of 3-µg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).


Assuntos
Vacina BNT162 , COVID-19 , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Adulto Jovem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacina BNT162/administração & dosagem , Vacina BNT162/efeitos adversos , Vacina BNT162/imunologia , Vacina BNT162/uso terapêutico , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinas/efeitos adversos , Vacinas/uso terapêutico , Imunogenicidade da Vacina , Resultado do Tratamento , Eficácia de Vacinas
2.
N Engl J Med ; 386(1): 35-46, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34752019

RESUMO

BACKGROUND: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. METHODS: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-µg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. RESULTS: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 µg, 20 µg, or 30 µg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 µg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). CONCLUSIONS: A Covid-19 vaccination regimen consisting of two 10-µg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

3.
N Engl J Med ; 385(3): 239-250, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34043894

RESUMO

BACKGROUND: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. METHODS: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 µg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed. RESULTS: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). CONCLUSIONS: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.).


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Adolescente , Adulto , Fatores Etários , Vacina BNT162 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Criança , Feminino , Humanos , Imunoglobulina G/sangue , Injeções Intramusculares/efeitos adversos , Masculino , Dor/etiologia , Resultado do Tratamento , Adulto Jovem
4.
Environ Sci Technol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904350

RESUMO

The frequency and intensity of global wildfires are escalating, leading to an increase in derived pyrogenic dissolved organic matter (pyDOM), which potentially influences the riverine carbon reservoir and poses risks to drinking water safety. However, changes in pyDOM properties as it traverses through soil to water bodies are highly understudied due to the challenges of simulating such processes under laboratory conditions. In this study, we extracted soil DOM along hillslope gradients and soil depths in both burned and unburned catchments post wildfire. Using high-resolution mass spectrometry and a substrate-explicit model, we observed significant increases in the relative abundance of condensed aromatics (ConAC) and tannins in wildfire-affected soil DOM. Wildfire-affected soil DOM also displayed a broader spectrum of molecular and thermodynamic properties, indicative of its diverse composition and reactivity. Furthermore, as the fire-induced weakening of topsoil microbial reprocessing abilities hindered the transformation of plant-derived DOM, the relative abundance of lignin-like compounds increased with soil depth in the fire regions. Meanwhile, the distribution of shared molecular formulas along the hillslope gradient (from shoulder to toeslope) exhibited analogous patterns in both burned and unburned catchments. Although there was an increased prevalence of ConAC and tannin in the burned catchments, the relative abundance of these fractions diminished along the hillslope in all three catchments. Based on the substrate-explicit model, the biodegradability exhibited by wildfire-affected DOM fractions offers the possibility of its conversion along hillslopes. Our findings reveal the spatial distribution of DOM properties after a wildfire, facilitating accurate evaluation of dissolved organic carbon composition involved in the watershed-scale carbon cycle.

5.
Arch Gynecol Obstet ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951259

RESUMO

PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.

6.
J Am Chem Soc ; 145(38): 20825-20836, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37589185

RESUMO

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small-molecule magnetic resonance probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis non-invasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that, for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, makes them strong candidates for clinical translation.


Assuntos
Ácido 2-Aminoadípico , Aldeídos , Camundongos , Animais , Ácido 2-Aminoadípico/química , Imageamento por Ressonância Magnética , Pulmão
7.
Anal Chem ; 95(8): 4024-4032, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36799513

RESUMO

Liver injury can result from various risk factors including diabetes, virus, alcohol, drugs, and other toxins, which is mainly responsible for global mortality and morbidity. Selenocysteine (Sec), as the main undertaker of selenium function in the life system, features prominently in a series of hepatic injuries and has close association with the pathological progression of liver injuries. Here, we report a mitochondria-targetable lanthanide complex-based probe, Mito-NPTTA-Tb3+/Eu3+, that can be used for accurately determining Sec in live cells and laboratory animals via the ratiometric time-gated luminescence (TGL) technique. This probe is composed of 2,2':6',2″-terpyridine-Tb3+/Eu3+ mixed complexes as the luminophore, 2,4-dinitrophenyl (DNP) as the responsive moiety and a lipophilic triphenylphosphonium cation (PPh3+) as the mitochondria-targeting moiety. Upon reaction with Sec, accompanied by the cleavage of DNP from the probe molecule, the I540/I690 ratio of the probe increased by 55 times, which enabled Sec to be detected with the ratiometric TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in mitochondria to allow the mitochondrial Sec to be successfully imaged under the ratiometric TGL mode. Importantly, using this probe coupled with the ratiometric TGL imaging technique, the fluctuations of liver Sec in various liver injuries of model mice induced by diabetes, drug, toxin, and alcohol were precisely monitored, revealing that Sec plays an important antioxidant role during the oxidative stress process in liver injury, and the Sec levels have a close interrelationship with the degree of liver injury. All the results suggest that the new probe Mito-NPTTA-Tb3+/Eu3+ could be a potential tool for the accurate diagnosis of liver injury.


Assuntos
Elementos da Série dos Lantanídeos , Selenocisteína , Camundongos , Animais , Luminescência , Fígado , Mitocôndrias , Corantes Fluorescentes
8.
Cytotherapy ; 25(6): 625-639, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36868991

RESUMO

BACKGROUND AIMS: Sepsis is a potentially life-threatening disease that results from a severe systemic inflammatory response due to infection. Mesenchymal stromal cell-derived small extracellular vesicles (MSC sEVs) are able to transfer bioactive molecules and have been demonstrated to play an important role in the pathophysiological process of sepsis. Herein the authors aimed to investigate the potential role and downstream molecular mechanism of MSC sEVs in sepsis. METHODS: MSC sEVs were acquired by ultracentrifugation and then injected into a cecal ligation and puncture mouse model. The efficacy of MSC sEVs in both in vitro and in vivo models of sepsis was evaluated. RESULTS: MSC sEV therapy improved survival, reduced sepsis-induced inflammation, attenuated pulmonary capillary permeability and improved liver and kidney function in septic mice. In addition, the authors found that microRNA-21a-5p (miR-21a-5p) was highly enriched in MSC sEVs, could be transferred to recipient cells, inhibited inflammation and increased survival in septic mice. Furthermore, the authors demonstrated that MSC sEV miR-21a-5p suppressed inflammation by targeting toll-like receptor 4 and programmed cell death 4. The therapeutic efficacy of MSC sEVs was partially abrogated by transfection with miR-21a-5p inhibitors. CONCLUSIONS: Collectively, the authors' data suggest that miR-21a-5p-bearing MSC sEVs may be a prospective and effective sepsis therapeutic strategy.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Sepse , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Estudos Prospectivos , Vesículas Extracelulares/metabolismo , Inflamação/terapia , Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Sepse/terapia
9.
J Biochem Mol Toxicol ; 37(3): e23270, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36593721

RESUMO

Myocardial infarction (MI) is an instant ischemic death of cardiomyocytes that remains a major global cause of mortalities. MI is accompanied by oxidative, inflammatory, apoptotic, and fibrotic insults. Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)-mediated MI. Rats were either injected with ISO (85 mg/kg, subcutaneously) or pretreated with PCA (100 or 200 mg/kg, orally). PCA supplementation markedly normalized ISO-induced disturbed cardiac function markers (creatine kinase-MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase-3, transforming growth factor-ß1 and matrix metalloproteinase-9, and enhancing B-cell lymphoma 2 and tissue inhibitors of metalloproteinase-3. The cardiac histological screening further confirmed the PCA's protective action. The obtained data recommend PCA as an alternative therapeutic agent to attenuate the molecular, biochemical, and histological alterations associated with MI development.


Assuntos
Infarto do Miocárdio , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Infarto do Miocárdio/metabolismo , Antioxidantes/metabolismo , Isoproterenol/efeitos adversos , Agonistas Adrenérgicos beta/efeitos adversos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo
10.
Mar Drugs ; 21(4)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37103373

RESUMO

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3-36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC50 values of 5.5 and 3.5 µM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC50 values of 11.6, 7.2, 11.8, and 2.2 µM, respectively.


Assuntos
Ferroptose , Penicillium , Penicillium/química , Linhagem Celular Tumoral , Análise Espectral , Estrutura Molecular
11.
Chem Biodivers ; 20(7): e202300753, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269045

RESUMO

Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A (1) and 25 known secondary metabolites (2-26). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC50 values of 1.4 µM and 6.7 µM, respectively.


Assuntos
Hypocrea , Trichoderma , Humanos , Lactonas/farmacologia , Esteroides/farmacologia , Estrutura Molecular , Dicroísmo Circular
12.
Zhonghua Nan Ke Xue ; 29(3): 269-274, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38597710

RESUMO

Long non-coding RNA (lncRNA) is an RNA molecule transcribed by RNA polymerase II, longer than 200 nt, and not translated into proteins. During gonadal development and spermatogenesis, lncRNAs are involved in epigenetic mechanisms, including DNA methylation, chromatin remodeling, and histone tail modification, which play important regulatory roles at the transcriptional or post-transcriptional level. Epigenomics including lncRNA is considered to be the second dimension of DNA sequence that can be adapted to environmental factors to specifically regulate gene expressions in some cells. Based on the functional action mechanism of lncRNAs, we reviewed the advances in the studies of lncRNAs in the direction of spermatogenesis and male infertility and analyzed the potential of lncRNAs as a biomarker of male infertility. The potential application of lncRNA in the treatment of male infertility diseases can be further explored based on the lncRNA target, RNA interference, competitive binding closed target and structural disruption of lncRNAs.


Assuntos
Infertilidade Masculina , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Espermatogênese/genética , Epigênese Genética , Metilação de DNA , Infertilidade Masculina/genética
13.
Zhongguo Zhong Yao Za Zhi ; 48(22): 5993-6002, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114205

RESUMO

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.


Assuntos
Isquemia Encefálica , Demência Vascular , Humanos , Demência Vascular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , NF-kappa B/metabolismo , Antioxidantes , Colinérgicos
14.
Opt Express ; 30(3): 4492-4503, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35209684

RESUMO

Materials with both excellent frequency selective characteristic and ultralight mechanical properties are highly urgent demanded for its potential applications such as absorbing materials, artificial magnetic conductors, antenna and so on. However, although the research about materials with only excellent frequency selective characteristic or ultralight mechanical properties is advanced, in most cases, it is still a challenge that making a material possesses excellent frequency selective characteristic and ultralight mechanical properties simultaneously. So how to make the two properties achieving a high level simultaneously is a hot topic which remains to be solved. Herein, we proposed a novel and feasible strategy for achieving simultaneously excellent frequency selective characteristic and ultralight mechanical properties material. According to our strategy, the composite we designed behaviors as a FSS which can realize highly efficiency stop bands in 16.09-16.4GHz and 17.11-17.36GHz. At the same time, the composite can be regarded as an ultralight mechanical metamaterial. The relativity density of the composite can reduce to 431.99 Kg/m3, which have a distinct advantage compared with the dielectric layers that conversional FSS used. Moreover, Its elasticity modulus can reach 112.25 MPa and its bending stiffness can reach 90.54 N/mm. These performances show that although the density of the composite is reduced, the composite can still keep well mechanical properties. The strategy we proposed gives a good solution to the problem existing in the materials which desire both excellent frequency selective characteristic and ultralight mechanical properties. The composite is a designing example which can be applied in engineering. So the strategy is a guideline for researchers to achieve composite which owns both excellent frequency selective characteristic and ultralight mechanical properties.

15.
Opt Express ; 30(25): 45426-45435, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522948

RESUMO

In this work, a high temperature infrared (IR) and radar compatible stealthy metamaterial based on ultrathin high-entropy alloy are proposed. From room temperature to 600°C, the fabricated radar absorption layer (RAL) can have wideband absorption in X-band (8.2-12.4 GHz) with average absorption 78% owing to magnetic resonance and ohmic loss. The ultrathin high-entropy alloy film is further design as infrared shielding layer (ISL) due to low-emissivity property. The ISL and RAL consist of the IR-microwave compatible stealth metamaterial. It can give rise to the strong reduction of both radar wave reflection and infrared thermal emission. Its bandwidth (absorption over 90%) is 2.15 GHz. In the infrared atmosphere window, it can suppress a half of thermal radiation. This is realized by the subtle combination between the RAL and specifically designed ISL that control the infrared emission and microwave absorption. These results show that they are practically very promising for the application of a radar-infrared bi-stealth technology in high temperature environment.

16.
Opt Express ; 30(12): 20750-20761, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224812

RESUMO

The combination of metasurface and holographic technology is the most cutting-edge development, but most of the proposed designs are static and do not allow active changes through external stimulation after fabrication, which takes only a limited part of the advantage provided by metasurface. Here, we propose and demonstrate a switchable hybrid active metasurface hologram in the terahertz (THz) regime composed of dynamic pixels (VO2-CSRR) and static pixels (Au-CSRR) based on an intelligent algorithm, which can display some/all information in different temperature ranges. In particular, such performance shows excellent potential in the field of optical communication security, making it a promising candidate. To prove this possibility, we propose a scheme for optical information encryption/decryption and transmission, which takes metasurfaces as carriers of encrypted information and state/polarization/positions as the secret key components. Only when the two matches correctly can we get the hidden real information. The security of our proposed scheme has reached an unprecedented level, providing a new road for communication security.

17.
Opt Express ; 30(5): 7124-7136, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35299482

RESUMO

A multifunctional metasurface is capable of manipulating electromagnetic waves and achieving kaleidoscopic functions flexibly, which significantly improves the integration and utilization of a single metasurface and has become one of the hotspots in electromagnetics. However, the majority of designs to date can only operate for limited polarization states in half-space and are difficult to show diverse functions at the same time, which restrict the widespread applications of multifunctional metadevices. Herein, an inspiring strategy of a chiral transmission-reflection-selective bifunctional metasurface is proposed to generate two independent functions in co-polarized reflection channel for left-handed circular polarized (LCP) incidence utilizing rotation-induced geometric phase modulation and in co-polarized transmission channel for right-handed circular polarized (RCP) incidence utilizing scaling-induced propagation phase modulation, and both functions appear concurrently under arbitrary linear polarized (LP) incident waves. To verify the feasibility of this methodology, three proof-of-concept metadevices composed of a dual-mode orbital angular momentum (OAM) generator, a bifocal metalens and an integrated metadevice of OAM generator and metalens are constructed and their performances in simulations and experiments are in good accordance with the theoretical ones. This exotic design of bifunctional metasurface will open up a promising way for multifunctional metadevices in engineering applications.

18.
Environ Sci Technol ; 56(18): 13439-13448, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36069735

RESUMO

The rapid proliferation of planktonic algae induced by eutrophication and climate warming make algae dissolved organic matter (AOM) an important source of dissolved organic matter (DOM) in surface waters, but the understanding of the link between AOM composition and photo-reactivity/photo-transformation of DOM in aquatic systems is limited. Here, intracellular organic matter (IOM) from Microcystis aeruginosa was extracted and subjected to molecular weight (MW) fractionation. Results indicated that IOM had lower aromaticity and higher photosensitive activity compared to Suwannee River fulvic acid (SRFA). The photosensitive activity of IOM relied on both its molecular weight distribution and fluorescence components. The IOM fraction with the highest MW proteins had the lowest quantum yields of reactive intermediates (ΦRIs), which increased with the decrease of MW, while the fractions with more low-excitation tyrosine-like components had relatively higher ΦRIs. Parallel factor analysis and high-resolution mass spectrometry revealed that light radiation of IOM resulted in the composition transformation from tryptophan-like and tyrosine-like components to humic-like components, forming less aromatic and more saturated recalcitrant dissolved organic carbon. Our findings provide new insights into the photo-reactivity and photo-transformation of algae-derived organic matters and help to predict DOM formation involved in carbon cycling in water environment.


Assuntos
Matéria Orgânica Dissolvida , Triptofano , Carbono , Substâncias Húmicas/análise , Espectrometria de Massas , Plantas , Espectrometria de Fluorescência/métodos , Tirosina , Água
19.
Environ Sci Technol ; 56(19): 14120-14132, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36151962

RESUMO

Iron (Fe) minerals constitute a major control on organic carbon (OC) storage in soils and sediments. While previous research has mainly targeted Fe (oxyhydr)oxides, the impact of Fe sulfides and their subsequent oxidation on OC dynamics remains unresolved in redox-fluctuating environments. Here, we investigated the impact of dissolved organic matter (DOM) on FeS oxidation and how FeS and its oxidation may alter the retention and nature of DOM. After the anoxic reaction of DOM with FeS, FeS preferentially removed high-molecular-weight and nitrogen-rich compounds and promoted the formation of aqueous sulfurized organic molecules, according to Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS) analysis. When exposed to O2, FeS oxidized to nanocrystalline lepidocrocite and additional aqueous sulfurized organic compounds were generated. The presence of DOM decreased the particle size of the resulting nano-lepidocrocite based on Mössbauer spectroscopy. Following FeS oxidation, most solid-phase OC remained associated with the newly formed lepidocrocite via a monodentate chelating mechanism (based on FTIR analysis), and FeS oxidation caused only a slight increase in the solubilization of solid-phase OC. Collectively, this work highlights the under-appreciated role of Fe sulfides and their oxidation in driving OC transformation and preservation.


Assuntos
Carbono , Matéria Orgânica Dissolvida , Carbono/análise , Compostos Férricos , Ferro , Minerais , Nitrogênio/análise , Compostos de Nitrogênio , Oxirredução , Óxidos/análise , Solo , Sulfetos , Água
20.
Environ Res ; 215(Pt 2): 114406, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36152883

RESUMO

BACKGROUND: Residential greenness may decrease the risk for hyperuricemia in rural areas, but the urban-rural disparities in this association and underlying pathways have not been studied. OBJECTIVES: To investigate the associations and potential pathways between residential greenness and hyperuricemia in urban and rural areas. METHODS: The baseline survey of the China Multi-Ethnic Cohort (CMEC) was used. Hyperuricemia was defined as serum uric acid (SUA) > 417 µmol/L for men and >357 µmol/L for women. The satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were used to capture residential greenness. A propensity score inverse-probability weighting method was used to assess urban-rural differences in the associations between residential greenness and hyperuricemia, with possible mediation effects of physical activity (PA), body mass index (BMI), PM2.5, and NO2 examined by causal mediation analyses. RESULTS: A total of 72,372 participants were included. The increases in the EVI500m and NDVI500m residential greenness were associated with a decreased risk for hyperuricemia and the SUA level in both urban and rural areas. For example, each 0.1-unit increase in EVI500m was associated with a decreased hyperuricemia risk of 7% (OR = 0.93 [0.91, 0.96]) and a decreased SUA level of -1.77 µmol/L [-2.60, -0.93], respectively; such associations were stronger in urban areas for both the risk for hyperuricemia (OR = 0.84 [0.83, 0.86]) and SUA level (-7.18 µmol/L [-7.91, -6.46]). The subgroup analysis showed that the greenness-hyperuricemia/SUA association varied by age, sex, and annual household income. The percentage of the joint mediation effect of PA, BMI, PM2.5, and NO2 on the association between EVI500m and the risk for hyperuricemia was higher in urban (34.92%) than rural areas (15.40%). BMI, PM2.5, and PA showed significantly independently mediation effects for the greenness-hyperuricemia association in both rural and urban areas. CONCLUSIONS: Exposure to residential greenness was associated with a decreased risk for hyperuricemia, partially through the pathways of PA, BMI, PM2.5, and NO2, which varied in urban and rural areas.


Assuntos
Poluição do Ar , Hiperuricemia , Adulto , Feminino , Humanos , Masculino , China/epidemiologia , Hiperuricemia/epidemiologia , Dióxido de Nitrogênio , Material Particulado , Ácido Úrico
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