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The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1a-h), dithiocarbamate-Cu(II) complexes (2a-hCu) and disulfide derivatives (2a-e, 2i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7 and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1g may be a partial reversible inhibitor, while 2d and 2f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2d, 2f-Cu and 1g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2f-Cu and 2d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2d and 1g exhibit low cytotoxicity, whereas 2f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.
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"Green-covering and red-heart" Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the "green-covering" formed on the surface of Guanyin Tuqu (SQ) and the "red-heart" in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of "green-covering and red-heart" characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of "green" outside and "red" inside. This study provides fundamental information support for optimizing the production process of GRTQ.
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Ulcerative colitis (UC) is characterized by chronic non-recessive inflammation of the intestinal mucosa involving both innate and adaptive immune responses. Currently, new targeted therapies are urgently needed for UC, and neutrophil extracellular traps (NETs) are new therapeutic options. NETs are DNA-based networks released from neutrophils into the extracellular space after stimulation, in which a variety of granule proteins, proteolytic enzymes, antibacterial peptides, histones, and other network structures are embedded. With the deepening of the studies on NETs, their regulatory role in the development of autoimmune and autoinflammatory diseases has received extensive attention in recent years. Increasing evidence indicates that excess NETs exacerbate the inflammatory response in UC, disrupting the structure and function of the intestinal mucosal barrier and increasing the risk of thrombosis. Although NETs are usually assigned a deleterious role in promoting the pathological process of UC, they also appear to have a protective role in some models. Despite such progress, comprehensive reviews describing the therapeutic promise of NETs in UC remain limited. In this review, we discuss the latest evidence for the formation and degradation of NETs, focusing on their double-edged role in UC. Finally, the potential implications of NETs as therapeutic targets for UC will be discussed. This review aims to provide novel insights into the pathogenesis and therapeutic options for UC.
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Colite Ulcerativa , Armadilhas Extracelulares , Neutrófilos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Humanos , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colite Ulcerativa/terapia , Animais , Neutrófilos/imunologia , Neutrófilos/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismoRESUMO
Direct dehydrogenation of carboxylic acids to their unsaturated counterparts represents a valuable transformation for complex molecule synthesis, which, however, has been challenging to achieve. In addition, the current carbonyl desaturation methods are almost all based on oxidative conditions. Here we report an Ir-catalyzed redox-neutral transfer dehydrogenation approach to directly convert carboxylic acids to either α,ß- or ß,γ-unsaturated counterparts. These reactions avoid using oxidants or strong bases, thus, tolerating various functional groups. The combined experimental and computational mechanistic studies suggest that this transfer hydrogenation reaction involves directed C-H oxidative addition, ß-H elimination, and dihydride transfer to an alkene acceptor with C(sp3)-H reductive elimination as the turnover-limiting step.
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Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.
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A novel, to the best of our knowledge, approach to generate frequency-tunable microwave sources with low-phase-noise based on a Brillouin laser frequency comb is proposed and experimentally demonstrated. The Brillouin laser frequency comb is generated by combining stimulated Brillouin scattering, frequency shifting optical injection locking, modulation sideband optical injection locking (MSOIL), and four-wave mixing effects. By beating the generated comb lines, the microwave is generated with an extremely low-level phase noise of -120 dBc/Hz at a 10-kHz offset. The frequency of the microwave signal can be finely tuned in steps of a Brillouin cavity mode spacing (i.e., 2â MHz) and coarsely adjusted to integer times the applied RF signal frequency in the MSOIL unit. Remarkably, the phase noise of the microwave source can be kept at almost the same low level during the whole tuning process over the frequency range of 30-75â GHz. The proposed tunable low-phase-noise microwave generation approach has great potential applications in communications, radars, and metrology.
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We presented a case of a 34-year-old male with postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and secondary hypertrophic olivary degeneration (HOD). Due to recurrent dizziness and headache, the patient was diagnosed as brainstem cavernous malformations with recurrent hemorrhage and underwent resection. He subsequently developed unexplained abnormal mental behavior 1 month after the surgery, and diagnosed with LGI1 encephalitis. Six months later, cranial MRI showed HOD. This condition is rare in clinical practice,and a complex mechanism underlies the occurrence.
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Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Masculino , Adulto , Encefalite/complicações , Encefalite/diagnóstico por imagem , Núcleo Olivar/patologia , Núcleo Olivar/diagnóstico por imagem , Proteínas , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Hipertrofia , Degeneração OlivarRESUMO
Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
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Valvas Cardíacas , Hidrogéis , Ratos Sprague-Dawley , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Animais , Alicerces Teciduais/química , Anisotropia , Ratos , Hidrogéis/química , Materiais Biocompatíveis/química , Próteses Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , MasculinoRESUMO
Development of carbon materials with high activity was important for rapid degradation of emerging pollutants. In this paper, a novel nanoscale zero-valent iron-copper bimetallic biochar (nZVIC-BC) was synthesized by carbothermal reduction of waste pine wood and copper-iron layered double hydroxides (LDHs). Characterization and analysis of its structural, elemental, crystalline, and compositional aspects using XRD, FT-IR, SEM, and TEM confirmed the successful preparation of nZVIC-BC and the high dispersion of Fe-Cu nanoparticles in an ordered carbon matrix. The experimental results showed that the catalytic activity of nZVIC-BC (Kobs of 0.0219 min-1) in the degradation of tetracycline (TC) in anoxic water environment was much higher than that of Fe-BC and Cu-BC; the effective degradation rate reached 85%. It was worth noting that the negative effects of Ca2+, Mg2+, and H2PO4- on TC degradation at ionic strengths greater than 15 mg/L were due to competition for active sites. Good stability and reusability were demonstrated in five consecutive cycle tests for low leaching of iron and copper. Combined with free radical quenching experiments and XPS analyses, the degradation of TC under air conditions was only 62%, with hydroxyl radicals (·OH) playing a dominant role. The synergistic interaction between Fe2+/Fe3+ and Cu0/Cu+/Cu2+ under nitrogen atmosphere enhances the redox cycling process; π-π adsorption, electron transfer processes, and active [H] were crucial for the degradation of TC; and possible degradation pathways of TC were deduced by LC-MS, which identified seven major aromatic degradation by-products. This study will provide new ideas and materials for the treatment of TC.
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Carvão Vegetal , Cobre , Água Subterrânea , Ferro , Tetraciclina , Poluentes Químicos da Água , Cobre/química , Carvão Vegetal/química , Ferro/química , Poluentes Químicos da Água/química , Tetraciclina/química , Água Subterrânea/químicaRESUMO
Objective: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective. Methods: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain. Results: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD. Conclusion: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the mucosa of the colon and rectum. UC is characterized by recurrent episodes, often necessitating lifelong medication use, imposing a significant burden on patients. Current conventional and advanced treatments for UC have the disadvantages of insufficient efficiency, susceptibility to drug resistance, and notable adverse effects. Therefore, developing effective and safe drugs has become an urgent need. Autophagy is an intracellular degradation process that plays an important role in intestinal homeostasis. Emerging evidence suggests that aberrant autophagy is involved in the development of UC, and modulating autophagy can effectively alleviate experimental colitis. A growing number of studies have established that autophagy can interplay with endoplasmic reticulum stress, gut microbiota, apoptosis, and the NLRP3 inflammasome, all of which contribute to the pathogenesis of UC. In addition, a variety of intestinal epithelial cells, including absorptive cells, goblet cells, and Paneth cells, as well as other cell types like neutrophils, antigen-presenting cells, and stem cells in the gut, mediate the development of UC through autophagy. To date, many studies have found that natural products hold the potential to exert therapeutic effects on UC by regulating autophagy. This review focuses on the possible effects and pharmacological mechanisms of natural products to alleviate UC with autophagy as a potential target in recent years, aiming to provide a basis for new drug development.
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Autofagia , Produtos Biológicos , Colite Ulcerativa , Autofagia/efeitos dos fármacos , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Animais , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.
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Fibrinólise , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Coagulação Sanguínea , Adulto , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Biomarcadores/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismoRESUMO
Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It is mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for the development of more effective UC therapies remains a pressing task for current research. Ferroptosis is a newly identified form of regulated cell death characterized by iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in the pathological processes of numerous diseases. A growing body of evidence suggests that the pathogenesis of UC is associated with ferroptosis, and the regulation of ferroptosis provides new opportunities for UC treatment. However, the specific mechanisms by which ferroptosis participates in the development of UC remain to be more fully and thoroughly investigated. Therefore, in this review, we focus on the research advances in the mechanism of ferroptosis in recent years and describe the potential role of ferroptosis in the pathogenesis of UC. In addition, we explore the underlying role of the crosslinked pathway between ferroptosis and other mechanisms such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, and gut microbiota in UC. Finally, we also summarize the potential compounds that may act as ferroptosis inhibitors in UC in the future.
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Colite Ulcerativa , Ferroptose , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Animais , Microbioma Gastrointestinal , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Transdução de Sinais , Peroxidação de Lipídeos/efeitos dos fármacos , Terapia de Alvo MolecularRESUMO
BACKGROUND: The incidence of inflammatory bowel disease (IBD) is rising worldwide, but epidemiological data on children and adolescents are lacking. Understanding the global burden of IBD among children and adolescents is essential for global standardization of methodology and treatment options. METHODS: This is a cross-sectional study based on aggregated data. We estimated the prevalence and incidence of IBD in children and adolescents between 1990 and 2019 according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were used to compare the burden and trends between different regions and countries. RESULTS: In 2019, there were 25,659 new cases and 88,829 prevalent cases of IBD among children and adolescents globally, representing an increase of 22.8% and 18.5%, respectively, compared to 1990. Over the past 30 years, the incidence and prevalence of IBD among children and adolescents have been highest in high SDI regions, with the most significant increases in East Asia and high-income Asia Pacific. At the age level, incidence and prevalence were significantly higher in the 15-19-year-old age group, while the < 5-year-old group showed the most significant increase in incidence and prevalence. CONCLUSION: The incidence of IBD in children and adolescents is significantly on the rise in some countries and regions, and IBD will remain an important public health issue with extensive healthcare and economic costs in the future. The reported IBD burden in children and adolescents at the global, regional, and national levels will assist in the development of more precise health policies.
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Doenças Inflamatórias Intestinais , Humanos , Adolescente , Criança , Doenças Inflamatórias Intestinais/epidemiologia , Incidência , Prevalência , Pré-Escolar , Masculino , Feminino , Estudos Transversais , Adulto Jovem , Saúde Global , LactenteRESUMO
In angiosperms, the pollen tube enters the receptive synergid cell, where it ruptures to release its cytoplasm along with two sperm cells. This interaction is complex, and the exact signal transducers that trigger the bursting of pollen tubes are not well understood. In this study, we identify three homologous receptor-like cytoplasmic kinases (RLCKs) expressed in pollen tubes of Arabidopsis, Delayed Burst 1/2/3 (DEB1/2/3), which play a crucial role in this process. These genes produce proteins localized on the plasma membrane, and their knockout causes delayed pollen tube burst and entrance of additional pollen tubes into the embryo sac due to fertilization recovery. We show that DEBs interact with the Ca2+ pump ACA9, influencing the dynamics of cytoplasmic Ca2+ in pollen tubes through phosphorylation. These results highlight the importance of DEBs as key signal transducers and the critical function of the DEB-ACA9 axis in timely pollen tube burst in synergids.
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Proteínas de Arabidopsis , Arabidopsis , Tubo Polínico , Tubo Polínico/genética , Tubo Polínico/metabolismo , Tubo Polínico/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Pólen/genética , Pólen/metabolismo , Proteínas Quinases/metabolismo , Proteínas Quinases/genéticaRESUMO
With the proposal of the "biological-psychological-social" model, clinical decision-makers and researchers have paid more attention to the bidirectional interactive effects between psychological factors and diseases. The brain-gut-microbiota axis, as an important pathway for communication between the brain and the gut, plays an important role in the occurrence and development of inflammatory bowel disease. This article reviews the mechanism by which psychological disorders mediate inflammatory bowel disease by affecting the brain-gut-microbiota axis. Research progress on inflammatory bowel disease causing "comorbidities of mind and body" through the microbiota-gut-brain axis is also described. In addition, to meet the needs of individualized treatment, this article describes some nontraditional and easily overlooked treatment strategies that have led to new ideas for "psychosomatic treatment".
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Transtornos Mentais , Microbiota , Humanos , Encéfalo/metabolismo , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/metabolismo , Transtornos Mentais/metabolismoRESUMO
Exposure to endocrine-disrupting chemicals (EDCs) in freshwater systems has garnered increasing attention. A comprehensive analysis of the migration patterns, bioaccumulation, and consumer health risk of EDCs along the Xiangjiang River due to fish consumption from the river ecosystem was provided. Twenty natural and synthetic target EDCs were detected and analyzed from the water, sediments, and fish samples collected along the Xiangjiang River. There were significant correlations between the EDC concentrations in fish and the sediments. This revealed that EDCs in sediments play a dominant role in the uptake of EDCs by fish. The bioaccumulation factor and biota-sediment accumulation factor were calculated, with the highest values observed for nonylphenol. Pearson's correlation analysis showed that bisphenol A is the most reliable biological indicator of EDC contamination in fish. Furthermore, based on the threshold of toxicological concerns and the health risk with dietary intake, crucian carp and catfish from the Xiangjiang River pose a certain risk for children and pregnant women compared to grass carp. The Monte Carlo simulation results indicated a certain risk of cumulative ∑EDC exposure for local residents due to fish consumption.
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Disruptores Endócrinos , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Sedimentos Geológicos , Rios , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Disruptores Endócrinos/análise , Rios/química , Animais , Humanos , Sedimentos Geológicos/química , China , Medição de Risco , Bioacumulação , Contaminação de Alimentos/análiseRESUMO
Background: Previous studies have shown conflicting results regarding the impact of circulating antioxidants on the risk of inflammatory bowel disease (IBD). In this study, our intent was to investigate the causal relationship between circulating antioxidants and IBD using Mendelian randomization (MR). Methods: Instrumental variables for absolute circulating antioxidants (ascorbate, retinol, lycopene, and ß-carotene) and circulating antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbate, and retinol) were screened from published studies. We obtained outcome data from two genome-wide association study (GWAS) databases, including the international inflammatory bowel disease genetics consortium (IIBDGC, 14,927 controls and 5,956 cases for Crohn's disease (CD), 20,464 controls and 6,968 cases for ulcerative colitis (UC), and 21,770 controls and 12,882 cases for IBD) and the FinnGen study (375,445 controls and 1,665 cases for CD, 371,530 controls and 5,034 cases for UC, and 369,652 controls and 7,625 cases for IBD). MR analysis was performed in each of the two databases and those results were pooled using meta-analysis to assess the overall effect of exposure on each phenotype. In order to confirm the strength of the findings, we additionally conducted a replication analysis using the UK Biobank. Results: In the meta-analysis of the IIBDGC and FinnGen, we found that each unit increase in absolute circulating level of retinol was associated with a 72% reduction in the risk of UC (OR: 0.28, 95% CI: 0.10 to 0.78, P=0.015). The UC GWAS data from the UK Biobank also confirmed this causal relationship (OR: 0.99, 95% CI: 0.97 to 1.00, P=0.016). In addition, there was suggestive evidence that absolute retinol level was negatively associated with IBD (OR: 0.41, 95% CI: 0.18 to 0.92, P=0.031). No other causal relationship was found. Conclusion: Our results provide strong evidence that the absolute circulating level of retinol is associated with a reduction in the risk of UC. Further MR studies with more instrumental variables on circulating antioxidants, especially absolute circulating antioxidants, are needed to confirm our results.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Antioxidantes , Vitamina A , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Dieta , Doenças Inflamatórias Intestinais/genética , Colite Ulcerativa/genética , Doença de Crohn/genéticaRESUMO
Waveguide bends have become an interesting research direction because they allow highly curved light transmission in a limited space. Here, we propose waveguide bends supporting two TE modes by etching slots and adding germanium arcs in the inner side of a waveguide bend. Simulations show that the bending radius of our proposed base-mode T E 0 waveguide bend drops to 500 nm and its insertion loss (IL) is reduced to 0.13 dB with footprints as small as 0.75µm×0.75µm. For the higher-order T E 1 mode waveguide bend, we adjust the introduced structure in combination with the light field distribution. The IL of the waveguide bend is also reduced to 0.18 dB with footprints as small as 1.85µm×1.85µm. T E 0 mode has 410 nm bandwidth in the optical communication band while T E 1 mode has 330 nm bandwidth by keeping I L<0.5d B. Through the analysis of these structural characteristics, we believe that this method still has great potential in higher-order mode transmission.
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While surface defects and heteroatom doping exhibit promising potential in augmenting the electrocatalytic hydrogen evolution reaction (HER), their performance remains unable to rival that of the costly Pt-based catalysts. Yet, the concurrent modification of catalysts by integrating both approaches stands as a promising strategy to effectively address the aforementioned limitation. In this work, tungsten dopants are introduced into self-supported CoFe-layered double hydroxides (LDH) on nickel foam using a hydrothermal method, and oxygen vacancies (Ov) are further introduced through calcination. The analysis results demonstrated that tungsten doping reduces the Ov formation energy of CoFeW-LDH. The Ov acted as oxophilic sites, facilitating water adsorption and dissociation, and reducing the barrier for cleaving HOâH bonds from 0.64 to 0.14 eV. Additionally, Ov regulated the electronic structure of CoFeW-LDH to endow optimized hydrogen binding ability on tungsten atoms, thereby accelerating alkaline Volmer and Heyrovsky reaction kinetics. Specifically, the abundance of Ov induced a transition of tungsten from a six-coordinated to highly active four-coordinated structure, which becomes the active site for HER. Consequently, an ultra-low overpotential of 41 mV at 10 mA cm-2, and a low Tafel slope of 35 mV dec-1 are achieved. These findings offer crucial insights for the design of efficient HER electrocatalysts.