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1.
Nature ; 565(7737): 67-72, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30568304

RESUMO

Although abundant in organic molecules, carbon-hydrogen (C-H) bonds are typically considered unreactive and unavailable for chemical manipulation. Recent advances in C-H functionalization technology have begun to transform this logic, while emphasizing the importance of and challenges associated with selective alkylation at a sp3 carbon1,2. Here we describe iron-based catalysts for the enantio-, regio- and chemoselective intermolecular alkylation of sp3 C-H bonds through carbene C-H insertion. The catalysts, derived from a cytochrome P450 enzyme in which the native cysteine axial ligand has been substituted for serine (cytochrome P411), are fully genetically encoded and produced in bacteria, where they can be tuned by directed evolution for activity and selectivity. That these proteins activate iron, the most abundant transition metal, to perform this chemistry provides a desirable alternative to noble-metal catalysts, which have dominated the field of C-H functionalization1,2. The laboratory-evolved enzymes functionalize diverse substrates containing benzylic, allylic or α-amino C-H bonds with high turnover and excellent selectivity. Furthermore, they have enabled the development of concise routes to several natural products. The use of the native iron-haem cofactor of these enzymes to mediate sp3 C-H alkylation suggests that diverse haem proteins could serve as potential catalysts for this abiological transformation, and will facilitate the development of new enzymatic C-H functionalization reactions for applications in chemistry and synthetic biology.


Assuntos
Biocatálise , Carbono/química , Carbono/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Hidrogênio/química , Ferro/química , Alquilação , Animais , Coenzimas/química , Coenzimas/metabolismo , Cisteína/metabolismo , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Evolução Molecular Direcionada , Heme/química , Heme/metabolismo , Hidrogênio/metabolismo , Ferro/metabolismo , Masculino , Metano/análogos & derivados , Metano/química , Serina/metabolismo , Especificidade por Substrato , Vitamina B 12/química , Vitamina B 12/metabolismo
2.
Proteomics ; : e2300359, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522029

RESUMO

Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.

3.
J Proteome Res ; 23(3): 1118-1128, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319990

RESUMO

The immune response is considered essential for pathology of ischemic stroke (IS), but it remains unclear which immune response-related proteins exhibit altered expression in IS patients. Here, we used Olink proteomics to examine the expression levels of 92 immune response-related proteins in the sera of IS patients (n = 88) and controls (n = 88), and we found that 59 of these proteins were differentially expressed. Feature variables were screened from the differentially expressed proteins by the least absolute shrinkage and selection operator (LASSO) and the random forest and by determining whether their proteins had an area under the curve (AUC) greater than 0.8. Ultimately, we identified six potential protein biomarkers of IS, namely, MASP1, STC1, HCLS1, CLEC4D, PTH1R, and PIK3AP1, and established a logistic regression model that used these proteins to diagnose IS. The AUCs of the models in the internal validation and the test set were 0.962 (95% confidence interval (CI): 0.895-1.000) and 0.954 (95% CI: 0.884-1.000), respectively, and the same protein detection method was performed in an external independent validation set (AUC: 0.857 (95% CI: 0.801-0.913)). These proteins may play a role in immune regulation via the C-type lectin receptor signaling pathway, the PI3K-AKT signaling pathway, and the B-cell receptor signaling pathway.


Assuntos
AVC Isquêmico , Humanos , Fosfatidilinositol 3-Quinases , Proteômica , Biomarcadores , Imunidade
4.
Plant Biotechnol J ; 22(1): 200-215, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37752705

RESUMO

Grain size is one of the important traits in wheat breeding programs aimed at improving yield, and cytokinins, mainly involved in cell division, have a positive impact on grain size. Here, we identified a novel wheat gene TaMADS-GS encoding type I MADS-box transcription factor, which regulates the cytokinins signalling pathway during early stages of grain development to modulate grain size and weight in wheat. TaMADS-GS is exclusively expressed in grains at early stage of seed development and its knockout leads to delayed endosperm cellularization, smaller grain size and lower grain weight. TaMADS-GS protein interacts with the Polycomb Repressive Complex 2 (PRC2) and leads to repression of genes encoding cytokinin oxidase/dehydrogenases (CKXs) stimulating cytokinins inactivation by mediating accumulation of the histone H3 trimethylation at lysine 27 (H3K27me3). Through the screening of a large wheat germplasm collection, an elite allele of the TaMADS-GS exhibits higher ability to repress expression of genes inactivating cytokinins and a positive correlation with grain size and weight, thus representing a novel marker for breeding programs in wheat. Overall, these findings support the relevance of TaMADS-GS as a key regulator of wheat grain size and weight.


Assuntos
Endosperma , Fatores de Transcrição , Fatores de Transcrição/genética , Endosperma/metabolismo , Triticum/metabolismo , Melhoramento Vegetal , Grão Comestível , Citocininas/metabolismo , Regulação da Expressão Gênica de Plantas/genética
5.
Metabolomics ; 20(1): 13, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180633

RESUMO

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical. OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension. METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension. RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957). CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.


Assuntos
Hipertensão , Lipidômica , Humanos , Estudos de Casos e Controles , Metabolômica , Biomarcadores , Ésteres do Colesterol , Triglicerídeos
6.
Plant Cell ; 33(3): 603-622, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955492

RESUMO

In wheat (Triticum aestivum L.), breeding efforts have focused intensively on improving grain yield and quality. For quality, the content and composition of seed storage proteins (SSPs) determine the elasticity of wheat dough and flour processing quality. Moreover, starch levels in seeds are associated with yield. However, little is known about the mechanisms that coordinate SSP and starch accumulation in wheat. In this study, we explored the role of the endosperm-specific NAC transcription factor TaNAC019 in coordinating SSP and starch accumulation. TaNAC019 binds to the promoters of TaGlu-1 loci, encoding high molecular weight glutenin (HMW-GS), and of starch metabolism genes. Triple knock-out mutants of all three TaNAC019 homoeologs exhibited reduced transcript levels for all SSP types and genes involved in starch metabolism, leading to lower gluten and starch contents, and in flour processing quality parameters. TaNAC019 directly activated the expression of HMW-GS genes by binding to a specific motif in their promoters and interacting with the TaGlu-1 regulator TaGAMyb. TaNAC019 also indirectly regulated the expression of TaSPA, an ortholog of maize Opaque2 that activates SSP accumulation. Therefore, TaNAC019 regulation of starch- and SSP-related genes has key roles in wheat grain quality. Finally, we identified an elite allele (TaNAC019-BI) associated with flour processing quality, providing a candidate gene for breeding wheat with improved quality.


Assuntos
Endosperma/metabolismo , Proteínas de Plantas/metabolismo , Amido/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Endosperma/genética , Glutens/genética , Glutens/metabolismo , Proteínas de Plantas/genética , Amido/genética , Fatores de Transcrição/genética , Triticum/genética , Triticum/metabolismo
7.
Environ Sci Technol ; 58(15): 6682-6692, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38547356

RESUMO

The atmospheric deposition of anthropogenic active nitrogen significantly influences marine primary productivity and contributes to eutrophication. The form of nitrogen deposition has been evolving annually, alongside changes in human activities. A disparity arises between observation results and simulation conclusions due to the limited field observation and research in the ocean. To address this gap, our study undertook three field cruises in the South China Sea in 2021, the largest marginal sea of China. The objective was to investigate the latest atmospheric particulate inorganic nitrogen deposition pattern and changes in nitrogen sources, employing nitrogen-stable isotopes of nitrate (δ15N-NO3-) and ammonia (δ15N-NH4+) linked to a mixing model. The findings reveal that the N-NH4+ deposition generally surpasses N-NO3- deposition, attributed to a decline in the level of NOx emission from coal combustion and an upswing in the level of NHx emission from agricultural sources. The disparity in deposition between N-NH4+ and N-NO3- intensifies from the coast to the offshore, establishing N-NH4+ as the primary contributor to oceanic nitrogen deposition, particularly in ocean background regions. Fertilizer (33 ± 21%) and livestock (20 ± 6%) emerge as the primary sources of N-NH4+. While coal combustion continues to be a significant contributor to marine atmospheric N-NO3-, its proportion has diminished to 22 (Northern Coast)-35% (background area) due to effective NOx emission controls by the countries surrounding the South China Sea, especially the Chinese Government. As coal combustion's contribution dwindles, the significance of vessel and marine biogenic emissions grows. The daytime higher atmospheric N-NO3- concentration and lower δ15N-NO3- compared with nighttime further underscore the substantial role of marine biogenic emissions.


Assuntos
Poluentes Atmosféricos , Carvão Mineral , Humanos , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Nitrogênio/análise , Isótopos de Nitrogênio/análise , China , Nitratos/análise , Poeira
8.
Orthod Craniofac Res ; 27(2): 220-227, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37578004

RESUMO

OBJECTIVES: To evaluate alveolar bone dimensions and its relationship with tooth movement (retraction, intrusion and torque) during orthodontic treatment with fixed appliance and clear aligners. METHODS: Thirty-two patients were included in this retrospective clinical study. Cone beam computed tomography (CBCT) was collected before and after treatment to measure the volume of dehiscence and fenestrations in the maxillary anterior region, anterior alveolar bone thickness and height and degree of tooth movement. Rank-sum tests were used to compare the differences in alveolar bone defect volumes between clear aligners and fixed appliance, multiple linear regression analysis was used for study evaluation, and kappa statistics were used to assess internal consistency and test-retest reliability. RESULTS: Post-operatively, most alveolar bone defects occurred on the labial side. The incidence of bone fenestration was 23.96% in the clear aligner group and 26.18% in the fixed appliance group, which was higher than the incidence of bone dehiscence (5.21%). The labial bone height decreased by 0.272 mm, and the palatal bone height increased by 0.617 mm for every 1 mm downward intrusion of the anterior tooth apex in the fixed appliance group. In the clear aligner group, there was no significant change in the labial bone height, and the palatal bone height decreased by 0.447 mm for every 1 mm of anterior tooth retraction coronally. CONCLUSIONS: In the fixed appliance group, anterior tooth intrusion and retraction may have led to alveolar bone resorption by its compression at the cervical level. This study provides a three-dimensional tooth movement evaluation method by using CBCT.


Assuntos
Incisivo , Aparelhos Ortodônticos Removíveis , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Maxila/cirurgia , Extração Dentária , Tomografia Computadorizada de Feixe Cônico , Remodelação Óssea , Técnicas de Movimentação Dentária , Aparelhos Ortodônticos Fixos
9.
Cardiol Young ; : 1-16, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602085

RESUMO

BACKGROUND: Kawasaki disease is a systemic vascular disease with an unclear pathophysiology that primarily affects children under the age of five. Research on immune control in Kawasaki disease has been gaining attention. This study aims to apply a bibliometric analysis to examine the present and future directions of immune control in Kawasaki disease. METHODS: By utilizing the themes "Kawasaki disease," "Kawasaki syndrome," and "immune control," the Web of Science Core Collection database was searched for publications on immune control in Kawasaki disease. This bibliometric analysis was carried out using VOSviewers, CiteSpace, and the R package "bibliometrix." RESULTS: In total, 294 studies on immune control in Kawasaki disease were published in Web of Science Core Collection. The three most significant institutions were Chang Gung University, the University of California San Diego, and Kaohsiung Chang Gung Memorial Hospital. China, the United States, and Japan were the three most important countries. In this research field, Clinical and Experimental Immunology was the top-referred journal, while the New England Journal of Medicine was the most co-cited journal. The Web of Science Core Collection document by McCrindle BW et al. published in 2017 was the most cited reference. Additionally, the author keywords concentrated on "COVID-19," "SARS-CoV-2," and "multisystem inflammatory syndrome in children" in recent years. CONCLUSION: The research trends and advancements in immune control in Kawasaki disease are thoroughly summarised in this bibliometric analysis, which is the first to do so. The data indicate recent research frontiers and hot directions, making it easier for researchers to study the immune control of Kawasaki disease.

10.
Sensors (Basel) ; 24(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38793855

RESUMO

Recently, due to physical aging, diseases, accidents, and other factors, the population with lower limb disabilities has been increasing, and there is consequently a growing demand for wheelchair products. Modern product design tends to be more intelligent and multi-functional than in the past, with the popularization of intelligent concepts. This supports the design of a new, fully functional, intelligent wheelchair that can assist people with lower limb disabilities in their day-to-day life. Based on the UCD (user-centered design) concept, this study focused on the needs of people with lower limb disabilities. Accordingly, the demand for different functions of intelligent wheelchair products was studied through a questionnaire survey, interview survey, literature review, expert consultation, etc., and the function and appearance of the intelligent wheelchair were then defined. A brain-machine interface system was developed for controlling the motion of the intelligent wheelchair, catering to the needs of disabled individuals. Furthermore, ergonomics theory was used as a guide to determine the size of the intelligent wheelchair seat, and eventually, a new intelligent wheelchair with the features of climbing stairs, posture adjustment, seat elevation, easy interaction, etc., was developed. This paper provides a reference for the design upgrade of the subsequently developed intelligent wheelchair products.


Assuntos
Interfaces Cérebro-Computador , Estudos de Viabilidade , Cadeiras de Rodas , Humanos , Pessoas com Deficiência , Desenho de Equipamento , Ergonomia/métodos , Design Centrado no Usuário , Inquéritos e Questionários
11.
Stroke ; 54(5): 1330-1339, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37094034

RESUMO

BACKGROUND: We projected global trends in ischemic stroke from 2020 to 2030 according to age, sex, and socio-demographic index (SDI) quintile. METHODS: Estimated annual percentage changes (EAPCs) were used to project trends in the incidence of deaths from and disability-adjusted life years (DALYs) due to ischemic stroke between 2020 and 2030. EAPCs were computed using generalized additive models and data from the Global Burden of Disease study during the 1990 to 2019 period. RESULTS: The global age-standardized incidence rate of ischemic stroke was projected to increase to 89.32 per 100 000 population in 2030 (EAPC=0.89), whereas the associated global age-standardized death and DALY rates were projected to decrease to 18.28 (EAPC, -3.58) and 500.37 per 100 000 (EAPC=-1.75), respectively, in 2030. The projections indicated a higher age-standardized incidence rate of ischemic stroke among women than among men in 2030 (90.70 versus 87.64 per 100 000). The incidence rate of ischemic stroke was projected to increase across all age groups and SDI quintiles between 2020 and 2030. At the national level, the greatest increase in the age-standardized incidence rate of ischemic stroke between 2020 and 2030 was projected to occur in Cyprus (EAPC=4.16), followed by Palestine (EAPC=3.50) and South Africa (EAPC=2.64). Additionally, the projections suggested increases in the age-standardized death and DALY rates due to ischemic stroke for countries in low-SDI quintiles (EAPC=3.68 and EAPC=5.30, respectively). CONCLUSIONS: The projections indicated that the incidence rate of ischemic stroke will increase both sexes, all age groups, and all SDI quintiles and in some countries between 2020 and 2030. Furthermore, countries with a low SDI should be aware of potential increases in the age-standardized death and DALY due to ischemic stroke.


Assuntos
Anos de Vida Ajustados por Deficiência , AVC Isquêmico , Masculino , Humanos , Feminino , Incidência , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Saúde Global
12.
Biochem Biophys Res Commun ; 667: 25-33, 2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37207561

RESUMO

OBJECTIVES: Changes of macrophage in the local immune microenvironment of periodontitis cause alveolar bone resorption. This study aims to investigate the effect of a new drug delivery method of aspirin on the immune microenvironment of periodontitis to promote alveolar bone repair, and to explore mechanism of aspirin's effect on macrophage. METHODS: We isolated extracellular vesicles (EVs) from periodontal stem cells (PDLSCs) and loaded with aspirin by sonication, and then evaluated the treatment efficacy of aspirin-loaded vesicles (EVs-ASP) in periodontitis model in mice. In vitro, we explored the role of EVs-ASP in the regulation of LPS-induced macrophages. The underlying mechanism by which EVs-ASP regulates phenotypic remodeling of macrophages in periodontitis was further investigated. RESULTS: EVs-ASP inhibited the inflammatory environment of LPS-induced macrophage, and promoted anti-inflammatory macrophages formation both in vivo and in vitro, and reduced bone loss in periodontitis models. Moreover, EVs-ASP enhanced oxidative phosphorylation and suppressed glycolysis in macrophages. CONCLUSIONS: Consequently, EVs-ASP improves the periodontal immune microenvironment by enhancing oxidative phosphorylation (OXPHOS) in macrophages, resulting in a certain degree of regeneration of alveolar bone height. Our study provides a new potential strategy for bone repair in periodontitis therapy.


Assuntos
Vesículas Extracelulares , Periodontite , Camundongos , Animais , Aspirina/farmacologia , Aspirina/metabolismo , Lipopolissacarídeos/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Macrófagos/metabolismo , Vesículas Extracelulares/metabolismo , Fenótipo
13.
Opt Express ; 31(19): 30932-30946, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710625

RESUMO

In this paper, we investigate the singular multi-wavelength and multi-waveband transparencies generated by P T-symmetric dumbbell optical waveguide networks composed of two materials, and obtain the number regularity for the transparency wavelengths of one-unit-cell system and the general relationships for the transmission and reflection coefficients of multi-unit-cell systems. Consequently, three types of exact transparencies produced by multi-unit-cell systems are found based on the aforementioned formulas: (i)exact multi-wavelength unidirectional or bidirectional transparency as the same as those of one-unit-cell system; (ii)exact multi-wavelength bidirectional transparency at which one-unit-cell system cannot produce exact transparency, generated by adjusting the number of unit cells; (iii)exact multi-wavelength bidirectional transparency at which one-unit-cell system produces exact transparency, also generated by adjusting the number of unit cells. It provides theoretical foundations for developing highly sensitive and multi-wavelength optical filters. On the other hand, we also discover that multi-unit-cell systems can create approximate multi-waveband bidirectional transparencies by adjusting the number of unit cells, which provides scientific support for developing high-performance optical stealth devices.

14.
Cardiovasc Diabetol ; 22(1): 34, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797706

RESUMO

BACKGROUND: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations. METHODS: A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations. RESULTS: During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index's association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio's association with CVD, respectively. CONCLUSIONS: Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Dislipidemias , Hipertensão , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Triglicerídeos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol , Glucose , Bancos de Espécimes Biológicos , Glicemia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Reino Unido/epidemiologia , Fatores de Risco , Biomarcadores
15.
J Nutr ; 153(6): 1730-1741, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37003507

RESUMO

BACKGROUND: Although dietary factors play a crucial role in the incidence of cardiovascular disease (CVD), the specific dietary risk factors vary across regions and require further investigation. OBJECTIVE: We aimed to analyze the burden of CVD due to different dietary factors by sex, age, and sociodemographic index (SDI) for 204 countries and territories between 1990 and 2019. METHODS: Data were extracted from the Global Burden of Disease 2019 and analyzed to determine population attributable fractions (PAFs), mortality, disability-adjusted life years (DALYs), and trends thereof, for CVDs attributable to dietary risk factors from 1990 to 2019. We used a generalized linear model with a Gaussian distribution to calculate the estimated annual percentage changes (EAPCs) in CVD mortality and DALY rates attributable to dietary risk factors. We also used a comparative risk-assessment framework to estimate CVD mortality and DALYs attributable to dietary risk factors. RESULTS: Approximately 40% of CVD mortality and DALY rates were attributable to dietary risk factors, with high-sodium intake, low whole grain intake, and low legume intake being the greatest dietary risk factors globally. Moreover, high SDI regions had the highest PAFs for CVD mortality and DALYs associated with high red and processed meat intake, middle SDI regions had the highest PAFs with high-sodium intake, and low SDI regions had the highest PAFs with low fruit and vegetable intake. The highest PAFs for CVD mortality and DALYs were associated with low whole grain intake in 13 and 9 regions, respectively. CONCLUSION: Reducing sodium intake and increasing whole grain and legume intake should be the top priority worldwide for improving regional diets and thereby decreasing CVD burdens. Other priorities should be set for regions with different SDIs, depending on the predominant dietary risk factors for CVDs in the respective regions.


Assuntos
Doenças Cardiovasculares , Fabaceae , Sódio na Dieta , Humanos , Doenças Cardiovasculares/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Fatores de Risco , Verduras , Saúde Global
16.
Biomacromolecules ; 24(5): 2063-2074, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37010453

RESUMO

Overcoming cisplatin-based drug resistance in lung cancer remains an enormous challenge in clinical tumor therapy worldwide. Recent studies have reported that some Rab GTPases are involved in multiple aspects of tumor progression, including invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. In particular, Rab26 is essential to vital processes such as vesicle-mediated secretion, cell growth, apoptosis, and autophagy. In this study, we developed a nanosystem based on programmed DNA self-assembly of Rab26 siRNA-loaded nanoparticles (siRNP). We demonstrated that siRNP could be effectively transfected into cisplatin-resistant A549 (A549/DDP) cells. These siRab26-carrying nanoparticles induced apoptosis and inhibited the disruption of autophagy. The combination therapy of siRab26 knockdown with cisplatin could improve the antitumor therapy compared with a single one in vitro. In nude mice, siRNP enhanced the chemosensitivity of cisplatin-resistant cells and inhibited tumor xenograft development. These outcomes suggest that siRNP is an effective platform for lung cancer therapy in cases exhibiting drug resistance.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Nanoestruturas , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proliferação de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/farmacologia
17.
Crit Rev Food Sci Nutr ; 63(15): 2331-2347, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34553667

RESUMO

The efficacy of using time restricted eating (TRE) for weight management and to mitigate metabolic disorders in overweight and obese people remains debatable. This meta-analysis quantified the impact of TRE on weight loss and metabolic health in overweight and obese people. The pooled results were subjected to a random-effects modeling using Hartung-Knapp-Sidik-Jonkman (HKSJ) method. Additionally, subgroup analysis was conducted based on study types, randomized controlled trials (RCTs) vs. non-randomized studies of interventions (NRSIs). Pooled results showed that subjects on TRE regimen (> 4 weeks) achieved a significant weight loss in comparison with unrestricted time regimen (weighted mean difference: -2.32%; 95% CI: -3.50, -1.14%; p < 0.01); however, weight loss was mainly attributed to the loss of lean mass rather than fat mass. The magnitude of weight loss was inversely correlated with daily fasting duration in RCTs. TRE significantly decreased the diastolic blood pressure and fasting insulin. An increase of low-density lipoprotein cholesterol (LDL-C) was observed in the TRE group. Favorable effect of TRE was observed on glucose metabolism but not on lipid profiles independent of weight loss. Hence TRE shall be administered with caution to overweight and obese people who have comorbidities such as dyslipidemia and sarcopenia.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1974335.


Assuntos
Obesidade , Sobrepeso , Humanos , Sobrepeso/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/terapia , LDL-Colesterol , Redução de Peso
18.
Inorg Chem ; 62(6): 2760-2768, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36724472

RESUMO

A stable metal-organic framework with the formula {[Co(BBZB)(IPA)]·H2O}n (JXUST-23, BBZB = 4,7-bis(1H-benzimidazole-1-yl)-2,1,3-benzothiadiazole and H2IPA = isophthalic acid) was constructed by incorporating Co2+ ions and two conjugated ligands under solvothermal conditions. JXUST-23 takes a dinuclear cluster-based layer structure with a porosity of 2.7%. In this work, JXUST-23 was used to activate peroxymonosulfate (PMS) to degrade rhodamine B (RhB), a difficult-to-degrade pollutant in water. Compared with pure PMS or JXUST-23, the JXUST-23/PMS system displays the best degradation ability of RhB in neutral solution. When the mass ratio of JXUST-23 to PMS was 2:3, 99.72% of RhB (50 ppm) was removed within 60 min, and the reaction rate was 0.1 min-1. Furthermore, free radical quenching experiments show that SO4•- was the main free radical during the process of RhB degradation. In addition, JXUST-23 exhibits good reusability for the degradation of the organic dye RhB, making it a potential candidate for environmental remediation.

19.
Cell Biol Toxicol ; 39(6): 2467-2499, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37491594

RESUMO

The central nervous system regulates all aspects of physiology to some extent. Neurodegenerative diseases (NDDs) lead to the progressive loss and dysfunction of neurons, which are particularly evident in Alzheimer's disease, Parkinson's disease, and many other conditions. NDDs are multifactorial diseases with complex pathogeneses, and there has been a rapid increase in the prevalence of NDDs. However, none of these diseases can be cured, making the development of novel treatment strategies an urgent necessity. Numerous studies have indicated how pyroptosis induces inflammation and affects many aspects of NDD. Therefore, components related to pyroptosis are potential therapeutic candidates and are attracting increasing attention. Here, we review the role of pyroptosis in the pathogenesis of NDDs and potential treatment options. Additionally, several of the current drugs and relevant inhibitors are discussed. Through this article, we provide theoretical support for exploring new therapeutic targets and updating clinical treatment strategies for NDDs. Notably, pyroptosis, a recently widely studied mode of cell death, is still under-researched compared to other traditional forms of cell death. Moreover, the focus of research has been on the onset and progression of NDDs, and the lack of organ-specific target discovery and drug development is a common problem for many basic studies. This urgent problem requires scientists and companies worldwide to collaborate in order to develop more effective drugs against NDDs.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Piroptose , Doença de Parkinson/metabolismo , Desenvolvimento de Medicamentos
20.
Environ Sci Technol ; 57(39): 14602-14610, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37713478

RESUMO

Deep-sea sediments (>1000 m) are often considered to be the ultimate sink for black carbon (BC), and the long-term buried BC in these sediments is believed to potentially provide a negative feedback effect on climate warming. The burial flux of BC in marine sediments is predominantly estimated based on soot BC (SBC) in most studies, frequently ignoring the contribution of char BC (CBC). While this methodology may result in an underestimation of the BC burial flux, the precise extent of this underestimation is yet to be determined. This study used the benzene poly(carboxylic acid) (BPCA) method and chemothermal oxidation (CTO) method to analyze CBC and SBC in four deep-sea sediment cores from the Zhongnan seamount in the South China Sea, respectively. The CBC content increased from 0.026 ± 0.010% at the seamount upper part (1432 m) to 0.039 ± 0.012% at the seamount foot (4278 m), constituting approximately 25 to 42% of the SBC content. The content disparity between CBC and SBC diminishes as depth increases. In deep-sea sediments, biogeochemical factors influence the variation of CBC molecules with depth. In the seamount middle-upper part (1432 and 2465 m), highly condensed CBC gradually accumulated along the core downward profile. In the sediment core profile of the seamount middle-lower part (3497 m), benzenetricarboxylic acid and benzenetetracarboxylic acid content decreased while the BC condensation degree rose, i.e., less condensed CBC was preferentially consumed. Afterward, CBC molecules reached a relatively stable state at the seamount foot. This study reveals that CBC possesses the capacity for long-term carbon sequestration in deep-sea sediments, and its content is not negligible.


Assuntos
Sedimentos Geológicos , Fuligem , Sedimentos Geológicos/química , Fuligem/análise , Ácidos Carboxílicos , Carbono , China , Monitoramento Ambiental/métodos
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