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1.
Plant Cell ; 35(1): 529-551, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36200865

RESUMO

RNA C-to-U editing in organelles is essential for plant growth and development; however, the underlying mechanism is not fully understood. Here, we report that pentatricopeptide repeat (PPR)-E subclass proteins carry out RNA C-to-U editing by recruiting the trans deaminase PPR motifs, coiled-coil, and DYW domain-containing protein 1 (PCW1) in maize (Zea mays) mitochondria. Loss-of-function of bZIP and coiled-coil domain-containing PPR 1 (bCCP1) or PCW1 arrests seed development in maize. bCCP1 encodes a bZIP and coiled-coil domain-containing PPR protein, and PCW1 encodes an atypical PPR-DYW protein. bCCP1 is required for editing at 66 sites in mitochondria and PCW1 is required for editing at 102 sites, including the 66 sites that require bCCP1. The PCW1-mediated editing sites are exclusively associated with PPR-E proteins. bCCP1 interacts with PCW1 and the PPR-E protein Empty pericarp7 (EMP7). Two multiple organellar RNA editing factor (MORF) proteins, ZmMORF1 and ZmMORF8, interact with PCW1, EMP7, and bCCP1. ZmMORF8 enhanced the EMP7-PCW1 interaction in a yeast three-hybrid assay. C-to-U editing at the ccmFN-1553 site in maize required EMP7, bCCP1, and PCW1. These results suggest that PPR-E proteins function in RNA editing by recruiting the trans deaminase PCW1 and bCCP1, and MORF1/8 assist this recruitment through protein-protein interactions.


Assuntos
Edição de RNA , Zea mays , Zea mays/metabolismo , Edição de RNA/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Organelas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA
2.
Plant Physiol ; 195(1): 430-445, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38198212

RESUMO

The essential role of plastid translation in embryogenesis has been established in many plants, but a retrograde signal triggered by defective plastid translation machinery that may leads to embryogenesis arrest remains unknown. In this study, we characterized an embryo defective27 (emb27) mutant in maize (Zea mays), and cloning indicates that Emb27 encodes the plastid ribosomal protein S13. The null mutant emb27-1 conditions an emb phenotype with arrested embryogenesis; however, the leaky mutant emb27-2 exhibits normal embryogenesis but an albino seedling-lethal phenotype. The emb27-1/emb27-2 trans-heterozygotes display varying phenotypes from emb to normal seeds but albino seedlings. Analysis of the Emb27 transcription levels in these mutants revealed that the Emb27 expression level in the embryo corresponds with the phenotypic expression of the emb27 mutants. In the W22 genetic background, an Emb27 transcription level higher than 6% of the wild-type level renders normal embryogenesis, whereas lower than that arrests embryogenesis. Mutation of Emb27 reduces the level of plastid 16S rRNA and the accumulation of the plastid-encoded proteins. As a secondary effect, splicing of several plastid introns was impaired in emb27-1 and 2 other plastid translation-defective mutants, emb15 and emb16, suggesting that plastome-encoded factors are required for the splicing of these introns, such as Maturase K (MatK). Our results indicate that EMB27 is essential for plastid protein translation, embryogenesis, and seedling development in maize and reveal an expression threshold of Emb27 for maize embryogenesis.


Assuntos
Regulação da Expressão Gênica de Plantas , Mutação , Proteínas de Plantas , Plastídeos , Plântula , Sementes , Zea mays , Zea mays/genética , Zea mays/embriologia , Plântula/genética , Plântula/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Plastídeos/genética , Plastídeos/metabolismo , Fenótipo , Splicing de RNA/genética , Íntrons/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
3.
Stroke ; 55(6): 1543-1553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38591228

RESUMO

BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.


Assuntos
Carga Global da Doença , Acidente Vascular Cerebral , Humanos , Adolescente , Criança , Pré-Escolar , Feminino , Masculino , Lactente , Acidente Vascular Cerebral/epidemiologia , Carga Global da Doença/tendências , Adulto Jovem , Incidência , Recém-Nascido , Saúde Global , Fatores de Risco , Prevalência , Acidente Vascular Cerebral Hemorrágico/epidemiologia , AVC Isquêmico/epidemiologia , Hemorragia Cerebral/epidemiologia , Efeitos Psicossociais da Doença
4.
J Am Chem Soc ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025826

RESUMO

Asymmetric soft-stiff patch nanohybrids with small size, spatially separated organics and inorganics, controllable configuration, and appealing functionality are important in applications, while the synthesis remains a great challenge. Herein, based on polymeric single micelles (the smallest assembly subunit of mesoporous materials), we report a dynamic surface-mediated anisotropic assembly approach to fabricate a new type of small asymmetric organic/inorganic patch nanohybrid for the first time. The size of this asymmetric organic/inorganic nanohybrid is ∼20 nm, which contains dual distinct subunits of a soft organic PS-PVP-PEO single micelle nanosphere (12 nm in size and 632 MPa in Young' modulus) and stiff inorganic SiO2 nanobulge (∼8 nm, 2275 MPa). Moreover, the number of SiO2 nanobulges anchored on each micelle can be quantitatively controlled (from 1 to 6) by dynamically tuning the density (fluffy or dense state) of the surface cap organic groups. This small asymmetric patch nanohybrid also exhibits a dramatically enhanced uptake level of which the total amount of intracellular endocytosis is about three times higher than that of the conventional nanohybrids.

5.
N Engl J Med ; 385(12): 1067-1077, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34459569

RESUMO

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Hipossódica , Hipertensão/dietoterapia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Doenças Cardiovasculares/epidemiologia , China , Dieta Hipossódica/efeitos adversos , Feminino , Humanos , Hiperpotassemia/complicações , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Potássio na Dieta/efeitos adversos , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
6.
New Phytol ; 241(4): 1662-1675, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38058237

RESUMO

Ribosome biogenesis is a highly dynamic and orchestrated process facilitated by hundreds of ribosomal biogenesis factors and small nucleolar RNAs. While many of the advances are derived from studies in yeast, ribosome biogenesis remains largely unknown in plants despite its importance to plant growth and development. Through characterizing the maize (Zea mays) defective kernel and embryo-lethal mutant dek58, we show that DEK58 encodes an Rrp15p domain-containing protein with 15.3% identity to yeast Rrp15. Over-expression of DEK58 rescues the mutant phenotype. DEK58 is localized in the nucleolus. Ribosome profiling and RNA gel blot analyses show that the absence of DEK58 reduces ribosome assembly and impedes pre-rRNA processing, accompanied by the accumulation of nearly all the pre-rRNA processing intermediates and the production of an aberrant processing product P-25S*. DEK58 interacts with ZmSSF1, a maize homolog of the yeast Ssf1 in the 60S processome. DEK58 and ZmSSF1 interact with ZmCK2α, a putative component of the yeast UTP-C complex involved in the small ribosomal subunit processome. These results demonstrate that DEK58 is essential to seed development in maize. It functions in the early stage of pre-rRNA processing in ribosome biogenesis, possibly through interacting with ZmSSF1 and ZmCK2α in maize.


Assuntos
RNA Ribossômico , Zea mays , Zea mays/genética , Zea mays/metabolismo , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Ribossomos/metabolismo , Sementes/genética , Sementes/metabolismo , Processamento Pós-Transcricional do RNA/genética
7.
Reprod Biol Endocrinol ; 22(1): 58, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778410

RESUMO

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.


Assuntos
Aneuploidia , Blastocisto , Aprendizado Profundo , Diagnóstico Pré-Implantação , Humanos , Estudos Retrospectivos , Feminino , Diagnóstico Pré-Implantação/métodos , Adulto , Gravidez , Blastocisto/citologia , Testes Genéticos/métodos , Fertilização in vitro/métodos
8.
Ear Hear ; 45(3): 658-665, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38178304

RESUMO

OBJECTIVES: Otitis media is one of the most important causes of hearing loss at an early age. Effective vaccination with the routine 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in 2000. It has been gradually replaced by the pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine or the higher-valent 13-valent PCV (PCV-13) since 2010. Data on the change in otitis media burden in recent years are sparse at the global, regional, and national levels. DESIGN: The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates, and the average annual percentage changes (AAPCs) in otitis media in geographic populations worldwide from 1990 to 2019. These global trends were further analyzed by subgroup (age, sex, and sociodemographic index [SDI]). RESULTS: Globally, the all-age rate of prevalence (AAPC = -0.7, 95% confidence interval [CI] = -0.7 to -0.8), DALYs (AAPC = -1.0, 95% CI = -1.1 to -1.0), and mortality (AAPC = -6.8, 95% CI = -7.3 to -6.4) from otitis media decreased constantly between 1990 and 2019. The all-age rate of incidence decreased sharply between 2000 and 2009 with an AAPC of -1.2 (95% CI = -1.4 to -0.9) and continued the downward trend between 2010 and 2019 (AAPC = -0.2, 95% CI = -0.3 to -0.1). In 2019, children aged 1 to 4 years old had the highest incidence at 29,127.3 per 100,000 population, while young adults under 30 years old accounted for 91.3% of the incident cases. Individuals living in middle-SDI countries had the largest increase in the incidence of otitis media, with an AAPC of 0.3 (95% CI = 0.3 to 0.3) between 1990 and 2019. The incidence and DALYs from otitis media decreased with increasing SDI. Regionally, the largest increase in incidence was observed in high-income Asia Pacific, Eastern Europe, and Western Sub-Saharan Africa between 1990 and 2019. Nationally, the largest increase in the incidence of otitis media was observed in the Republic of Korea, with an AAPC of 0.8 (95% CI = 0.6 to 1.1) in the same time period. CONCLUSIONS: There have been successful previous endeavors to reduce DALYs and mortality attributed to otitis media on a global scale. The worldwide incidence of otitis media experienced a sharp decline following the introduction of PCV-7 in 2000, and this downward trend persisted in subsequent years with the adoption of PCV-13/pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Continual epidemiological surveillance of otitis media's global trends, pathogen distribution, and resistance patterns remains imperative.


Assuntos
Otite Média , Criança , Adulto Jovem , Humanos , Lactente , Pré-Escolar , Adulto , Vacinas Conjugadas , Otite Média/epidemiologia , Incidência , Pesquisa , República da Coreia , Anos de Vida Ajustados por Qualidade de Vida
9.
J Toxicol Environ Health A ; 87(11): 471-479, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38590254

RESUMO

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.


Assuntos
Doença de Alzheimer , Canabidiol , Disfunção Cognitiva , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Eixo Encéfalo-Intestino , Cognição , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças
10.
Mar Drugs ; 22(1)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38248665

RESUMO

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.


Assuntos
Quitosana , Neoplasias Pulmonares , Polietilenoglicóis , Polietilenoimina , Polifosfatos , Humanos , Animais , Camundongos , Nanogéis , Antioxidantes/farmacologia , Cloreto de Amônio , Benzimidazóis , Doxorrubicina/farmacologia , Compostos de Amônio Quaternário/farmacologia
11.
Angew Chem Int Ed Engl ; 63(23): e202403245, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38578838

RESUMO

The encapsulation of functional colloidal nanoparticles (100 nm) into single-crystalline ZSM-5 zeolites, aiming to create uniform core-shell structures, is a highly sought-after yet formidable objective due to significant lattice mismatch and distinct crystallization properties. In this study, we demonstrate the fabrication of a core-shell structured single-crystal zeolite encompassing an Fe3O4 colloidal core via a novel confinement stepwise crystallization methodology. By engineering a confined nanocavity, anchoring nucleation sites, and executing stepwise crystallization, we have successfully encapsulated colloidal nanoparticles (CN) within single-crystal zeolites. These grafted sites, alongside the controlled crystallization process, compel the zeolite seed to nucleate and expand along the Fe3O4 colloidal nanoparticle surface, within a meticulously defined volume (1.5×107≤V≤1.3×108 nm3). Our strategy exhibits versatility and adaptability to an array of zeolites, including but not restricted to ZSM-5, NaA, ZSM-11, and TS-1 with polycrystalline zeolite shell. We highlight the uniformly structured magnetic-nucleus single-crystalline zeolite, which displays pronounced superparamagnetism (14 emu/g) and robust acidity (~0.83 mmol/g). This innovative material has been effectively utilized in a magnetically stabilized bed (MSB) reactor for the dehydration of ethanol, delivering an exceptional conversion rate (98 %), supreme ethylene selectivity (98 %), and superior catalytic endurance (in excess of 100 hours).

12.
J Am Chem Soc ; 145(44): 24284-24293, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37888942

RESUMO

Zinc metal-based aqueous batteries (ZABs) offer a sustainable, affordable, and safe energy storage alternative to lithium, yet inevitable dendrite formation impedes their wide use, especially under long-term and high-rate cycles. How the battery can survive after dendrite formation remains an open question. Here, we pivot from conventional Zn dendrite growth suppression strategies, introducing proactive dendrite-digesting chemistry via a mesoporous Ti3C2 MXene (MesoTi3C2)-wrapped polypropylene separator. Spectroscopic characterizations and electrochemical evaluation demonstrate that MesoTi3C2, acting as an oxidant, can revive the formed dead Zn0 dendrites into electroactive Zn2+ ions through a spontaneous redox process. Density functional theory reveals that the abundant edge-Ti-O sites in our MesoTi3C2 facilitate high oxidizability and electron transfer from Zn0 dendrites compared to their in-plane counterparts. The resultant asymmetrical cell demonstrates remarkable ultralong cycle life of 2200 h at a practical current of 5 mA cm-2 with a low overpotential (<50 mV). The study reveals the unexpected edge effect of mesoporous MXenes and uncovers a new proactive dendrite-digesting chemistry to survive ZABs, albeit with inevitable dendrite formation.

13.
BMC Microbiol ; 23(1): 394, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38066426

RESUMO

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.


Assuntos
Tacrolimo , Animais , Camundongos , Imunossupressores/farmacologia , Metaboloma , Metabolômica
14.
Ophthalmology ; 130(6): 575-587, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36758807

RESUMO

PURPOSE: To provide estimates for regional and national burdens of blindness and vision loss among children and adolescents between 1990 and 2019 by disease, age, and sociodemographic index (SDI). DESIGN: This was a retrospective demographic analysis based on aggregated data. METHODS: This was a population-based study using 1990-2019 data on the burden of vision loss and blindness from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of vision loss and blindness was evaluated in terms of case numbers, rates per 100 000 population, and average annual percentage changes (AAPCs) in prevalence rates and years lived with disability (YLDs). RESULTS: Globally, the rates of blindness and vision loss per 100 000 population decreased in all age groups between 1990 and 2019, with prevalence rates decreasing from 1091.4 (95% uncertainty interval [UI], 895.2-1326.1) to 1036.9 (95% UI, 847.8-1265.9, AAPC, -0.2) and YLDs decreasing from 44.5 (95% UI, 28.1-66.5) to 40.2 (95% UI, 25.1-60.7, AAPC, -0.4). Most of these reductions in prevalence rates (AAPC, -0.2, 95% confidence interval [CI], -0.2 to -0.1) and YLDs (AAPC, -0.2, 95% CI, -0.3 to -0.2) were due to decreases in refractive disorder. Notably, near-vision loss prevalence (AAPC, 0.3, 95% CI, 0.2-0.4) and YLDs (AAPC, 0.3, 95% CI, 0.2-0.4) substantially increased in all age groups. Children and adolescents in low- and low-middle SDI countries exhibited substantial decreases in the prevalence rates and YLDs of blindness and vision loss, but their counterparts in high- and middle-high SDI countries experienced a substantial increase in prevalence. CONCLUSIONS: Globally, efforts in the past 3 decades have substantially decreased the burdens of blindness and vision loss among children and adolescents. However, there is extensive variation according to the kind of impairment, age group, and country SDI. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Carga Global da Doença , Saúde Global , Humanos , Criança , Adolescente , Estudos Retrospectivos , Prevalência , Cegueira/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida
15.
Clin Endocrinol (Oxf) ; 99(3): 342-349, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36806120

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is more prevalent in women, and women show a better prognosis than men; however, the factors contributing to this prognostic difference are confounding. Therefore, we aimed to investigate the effect of the interaction between sex and age on the prognosis of PTC. METHODS: A total of 108,459 patients with PTC were retrospectively analysed, and Cox-regression models were used to assess differences in disease specific survival (DSS) by sex, with inverse probability of treatment weighting (IPTW) to control for between-group differences in prognosis by sex due to age change. Restricted cubic splines were used to analyse prognostic differences between sexes for papillary thyroid microcarcinoma (PTMC) and PTC. Multiple mediation analyses were used to assess the direct or indirect effect of sex on DSS. RESULTS: The DSS was higher for women than men (98.6% vs. 95.4%, χ2 = 458.57, p < .001). After IPTW adjustment, the DSS of women was better than that of men (HR = 0.67, 0.60-0.76). In the subgroup analysis, women had an advantage in DSS across most age intervals (crude HR = 0.166 [0.082-0.337], p < .001, IPTW-adjusted HR = 0.331 [0.161-0.681], p < .001). The difference between the two gradually narrowed with increasing age, and the prognosis of women was better than that of men in PTMC, while this advantage was not obvious in PTC. CONCLUSIONS: The overall PTC prognosis of women is better than that of men, but the prognostic advantage of women diminishes with age and tumour growth. These differences in prognosis may be due to some indirect factors caused by different sexes.


Assuntos
Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Câncer Papilífero da Tireoide , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
16.
Pharmacol Res ; 187: 106625, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563870

RESUMO

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Depressão/tratamento farmacológico , Doenças Neuroinflamatórias , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia
17.
Chem Rev ; 121(23): 14349-14429, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34609850

RESUMO

Functional mesoporous materials have gained tremendous attention due to their distinctive properties and potential applications. In recent decades, the self-assembly of micelles and framework precursors into mesostructures on the liquid-solid, liquid-liquid, and gas-liquid interface has been explored in the construction of functional mesoporous materials with diverse compositions, morphologies, mesostructures, and pore sizes. Compared with the one-phase solution synthetic approach, the introduction of a two-phase interface in the synthetic system changes self-assembly behaviors between micelles and framework species, leading to the possibility for the on-demand fabrication of unique mesoporous architectures. In addition, controlling the interfacial tension is critical to manipulate the self-assembly process for precise synthesis. In particular, recent breakthroughs based on the concept of the "monomicelles" assembly mechanism are very promising and interesting for the synthesis of functional mesoporous materials with the precise control. In this review, we highlight the synthetic strategies, principles, and interface engineering at the macroscale, microscale, and nanoscale for oriented interfacial assembly of functional mesoporous materials over the past 10 years. The potential applications in various fields, including adsorption, separation, sensors, catalysis, energy storage, solar cells, and biomedicine, are discussed. Finally, we also propose the remaining challenges, possible directions, and opportunities in this field for the future outlook.


Assuntos
Engenharia , Micelas , Catálise , Porosidade
18.
J Nanobiotechnology ; 21(1): 171, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237292

RESUMO

Certain chemotherapeutics can induce tumor cells' immunogenic cell death (ICD), release tumor antigens, and thereby trigger personalized antitumor immune responses. Co-delivery of adjuvants using nanocarriers could amplify the ICD-induced tumor-specific immunity achieving a synergistic chemo-immunotherapeutic effect. However, complicated preparation, low drug loading efficiency, and potential carrier-associated toxicity are the major challenges that limited its clinical applications. Herein, a carrier-free core-shell nanoparticle (MPLA-CpG-sMMP9-DOX, MCMD NPs) was constructed by facile self-assembly of spherical nucleic acids (SNA) with two adjuvants of CpG ODN and monophosphoryl lipid A (MPLA) as a core and doxorubicin (DOX) radially around the dual-adjuvants SNA as a shell. The results demonstrated that MCMD NPs could enhance drugs accumulation in tumors, and release DOX upon enzymatic degradation of matrix metalloproteinase-9 (MMP-9) peptide in the tumor microenvironment (TME), which enhanced the direct-killing effect of DOX on tumor cells. The core of MPLA-CpG SNA efficiently boosted the ICD-induced antitumor immune response to further attack tumor cells. Thus, MCMD NPs achieved a synergistic therapeutic effect of chemo-immunotherapy with reduced off-target toxicity. This study provided an efficient strategy for the development of a carrier-free nano-delivery system for enhanced cancer chemo-immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Imunoterapia , Neoplasias/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia
19.
Ecotoxicol Environ Saf ; 255: 114742, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37032575

RESUMO

Cadmium (Cd) pollution in crops seriously affects the ecosystem and human health. Effective measures should be employed to reduce the absorption and accumulation of cadmium in crops. Currently, there are many pieces of research on the application of biochar (BC) and selenium (Se) alone to the remediation of soil Cd pollution; however, few investigations have been devoted to the application of BC and Se together to the remediation of soil Cd pollution. The peanut was taken as the target crop to explore the effects of exogenous selenium and biochar on the remediation of soil Cd pollution. The response of the soil bacterial community to two levels of Cd concentration and its relationship with soil properties and Cd availability are methodically investigated. This study sets two cadmium pollution concentrations of low Cd (5 mg/ kg) and high Cd (20 mg/kg), as well as six treatments: blank, BC, soil Se, soil Se-BC, leaf Se, and leaf Se-BC. The achieved results revealed that both Se and BC could noticeably enhance the yield of peanut seeds and reduce the Cd content in peanut seeds. Among them, Se-BC treatment on soil exhibits the most influence, which reduces the Cd content by 47.86%. Se and BC also affect the physical and chemical properties of soil and remarkably magnify the content of soil available phosphorus, organic matter, soil pH, and soil conductivity. For instance, then effect is detected in the case of applying selenium biochar to soil, leading to an increase of about 64.38%, 72.62%, 2.64%, and 61.15%, respectively, and reducing the content of soil available cadmium by 21.02%. Redundancy analysis confirms that these properties enhance the abundance of dominant bacteria Actinobacteria, Proteobacteria, and Chloroflexi. The correlation analysis also indicates that Saccharimonadales, Bacillus, Arthrobacter, and other bacteria with the function of reducing the bioavailability of cadmium in soil reveal a considerable positive correlation with the variations of physical and chemical properties. In general, exogenous Se and BC incorporate to drop the content of available Cd in the soil through direct passivation, passivation caused by soil environmental change, and passivation caused by altering the soil microbial community structure; as a result, the migration and enrichment of Cd in peanut seeds are blocked and reduced. Moreover, the mixed application of BC and soil Se exhibits the best effect.


Assuntos
Selênio , Poluentes do Solo , Humanos , Arachis/química , Cádmio/análise , Selênio/farmacologia , Selênio/análise , Solo/química , Ácido Selenioso , Ecossistema , Poluentes do Solo/análise , Carvão Vegetal/farmacologia , Carvão Vegetal/química , Bactérias , Produtos Agrícolas
20.
Ecotoxicol Environ Saf ; 267: 115662, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37939554

RESUMO

Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.


Assuntos
Monitoramento Biológico , Chumbo , Adsorção , Transporte Biológico , Biomineralização
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