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1.
Molecules ; 29(13)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38998938

RESUMO

The mechanics of capillary force in biological systems have critical roles in the formation of the intra- and inter-cellular structures, which may mediate the organization, morphogenesis, and homeostasis of biomolecular condensates. Current techniques may not allow direct and precise measurements of the capillary forces at the intra- and inter-cellular scales. By preserving liquid droplets at the liquid-liquid interface, we have discovered and studied ideal models, i.e., interfacial liquids and marbles, for understanding general capillary mechanics that existed in liquid-in-liquid systems, e.g., biomolecular condensates. The unexpectedly long coalescence time of the interfacial liquids revealed that the Stokes equation does not hold as the radius of the liquid bridge approaches zero, evidencing the existence of a third inertially limited viscous regime. Moreover, liquid transport from a liquid droplet to a liquid reservoir can be prohibited by coating the droplet surface with hydrophobic or amphiphilic particles, forming interfacial liquid marbles. Unique characteristics, including high stability, transparency, gas permeability, and self-assembly, are observed for the interfacial liquid marbles. Phase transition and separation induced by the formation of nanostructured materials can be directly observed within the interfacial liquid marbles without the need for surfactants and agitation, making them useful tools to research the interfacial mechanics.

2.
Molecules ; 29(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39202840

RESUMO

Polyglycolic acid (PGA) is a biologically friendly material with a wide range of applications. The production of dimethyl oxalate using coal-based syngas and the hydrogenation of dimethyl oxalate can produce the polymerization raw material of PGA, glycolide, which requires a methyl glycolate polymerization and depolymerization process. The intermediate products of the production process were analyzed using gas chromatogram-mass spectrometry (GC-MS) and Orbitrap mass spectrometry (Orbitrap MS), which revealed the presence of cyclic and linear PGAs with different capped ends. The impurities present in the oligomer were mostly methyl-capped PGA and were retained in the subsequent depolymerization process to glycolide, solvent washing can be used to remove this part of the impurity and ultimately obtain a refined glycolide product. Furthermore, it is proposed that the use of the specialized Kendrick Mass Defect (KMD) to plot and analyze PGA compounds obtained using mass spectrometry can enable the direct classification of PGAs without the need for exact molecular formula assignment.

3.
Angew Chem Int Ed Engl ; : e202412794, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291306

RESUMO

The widespread application of photocatalysis for converting solar energy and seawater into hydrogen is generally hindered by limited catalyst activity and the lack of sustainable large-scale platforms. Here, a multi-scale hierarchical organic photocatalytic platform was developed, combining a photosensitive molecular heterojunction with a molecular-scale gradient energy level alignment and micro-nanoscale hierarchical pore structures. The ternary system facilitates efficient charge transfer and enhances photocatalytic activity compared to conventional donor-acceptor pairs. Meanwhile, the super-wetted hierarchical interfaces of the platform endow it with the ability to repeatedly capture light and self-suspend below the water surface, which simultaneously improves the light utilization efficiency, and reduces the adverse effects of salt deposition. Under a Xe lamp illumination, the hydrogen evolution rate of this organic platform utilizing a sacrificial agent can reach 165.8 mmol h-1 m-2, exceeding that of mostly inorganic systems as reported. And upon constructing a scalable system, the platform produced 80.6 ml m-2 of hydrogen from seawater within five hours at noon. More importantly, the outcomes suggest an innovative multi-scale approach that bridges disciplines, advancing the frontier of sustainable seawater hydrogen production driven by solar energy.

4.
Crit Rev Food Sci Nutr ; : 1-25, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37493455

RESUMO

Tea contains a variety of bioactive components, including catechins, amino acids, tea pigments, caffeine and tea polysaccharides, which exhibit multiple biological activities. These functional components in tea provide a variety of unique flavors, such as bitterness, astringency, sourness, sweetness and umami, which meet the demand of people for natural plant drinks with health benefits and pleasant flavor. Meanwhile, the traditional process of tea plantation, manufacturing and circulation are often accompanied by the safety problems of pesticide residue, heavy metal, organic solvents and other exogenous risks. High-quality tea extract refers to the special tea extract obtained by enriching the specific components of tea. Through green and efficient extraction technologies, diversed high-quality tea extracts such as high-fragrance and high-amino acid tea extracts, low-caffeine and high-catechin tea extracts, high-bioavailability and high-theaflavin tea extracts, high-antioxidant and high-tea polysaccharide tea extracts, high-umami-taste and low-bitter and astringent taste tea extracts are produced. Furthermore, rapid detection, green control and intelligent processing are applied to monitor the quality of tea in real-time, which guarantee the stability and safety of high-quality tea extracts with enhanced efficiency. These emerging technologies will realize the functionalization and specialization of high-quality tea extracts, and promote the sustainable development of tea industry.


Main high-quality tea extracts and their preparation methods were introduced.Potential pollutants in the processing of tea extracts and their detection methods were proposed.Emerging intelligent processing technologies of tea extract were summarized.The applications of high-quality tea extracts in food industry were explored.Future trends of tea extracts and relevant suggestions were presented.

5.
Crit Rev Food Sci Nutr ; 63(25): 7598-7626, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35266837

RESUMO

Sleep disorders have received widespread attention nowadays, which have been promoted by the accelerated pace of life, unhealthy diets and lack of exercise in modern society. The chemical medications to improve sleep has shown serious side effects and risks with high costs. Therefore, it is urgent to develop efficient nutraceuticals from natural sources to ensure sleep quality as a sustainable strategy. As the second most consumed beverage worldwide, the health-promoting effects of tea have long been widely recognized. However, the modulatory effect of teas on sleep disorders has received much less attention. Tea contains various natural sleep-modulating active ingredients such as L-theanine (LTA), caffeine, tea polyphenols (TPP), tea pigments, tea polysaccharides (TPS) and γ-aminobutyric acid (GABA). This review focuses on the potential influence and main regulating mechanisms of different tea active ingredients on sleep, including being absorbed by the small intestine and then cross the blood-brain barrier to act on neurons in the brain as neurotransmitters, manipulating the immune system and further affect sleep-wake cycle by regulating the levels of cytokines, and controlling the gut microbes to maintain the homeostasis of circadian rhythm. Current research progress and limitations are summarized and several future development directions are also proposed. This review hopes to provide new insights into the future elucidation of the sleep-regulating mechanisms of different teas and their natural active ingredients and the development of tea-based functional foods for alleviating sleep disorders. HighlightsNatural sleep-modulating active ingredients in tea have been summarized.Influences of drinking tea or tea active ingredients on sleep are reviewed.Three main regulating mechanisms of tea active ingredients on sleep are explained.The associations among nervous system, immune system and intestinal microbiota are investigated.The potential of developing delivery carriers for tea active ingredients is proposed.


Assuntos
Microbioma Gastrointestinal , Transtornos do Sono-Vigília , Humanos , Chá , Sono , Polifenóis/farmacologia , Sistema Imunitário
6.
Compr Rev Food Sci Food Saf ; 22(4): 2945-2976, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37166996

RESUMO

Due to its rich health benefits and unique cultural charm, tea drinking is increasingly popular with the public in modern society. The safety of tea is the top priority that affects the development of tea industry and the health of consumers. During the process of tea growth, pesticides are used to prevent the invasion of pests and diseases with maintaining high quality and stable yield. Because hot water brewing is the traditional way of tea consumption, water is the main carrier for pesticide residues in tea into human body accompanied by potential risks. In this review, pesticides used in tea gardens are divided into two categories according to their solubility, among which water-soluble pesticides pose a greater risk. We summarized the methods of the sample pretreatment and detection of pesticide residues and expounded the migration patterns and influencing factors of tea throughout the process of growth, processing, storage, and consumption. Moreover, the toxicity and safety of pesticide residues and diseases caused by human intake were analyzed. The risk assessment and traceability of pesticide residues in tea were carried out, and potential eco-friendly improvement strategies were proposed. The review is expected to provide a valuable reference for reducing risks of pesticide residues in tea and ensuring the safety of tea consumption.


Assuntos
Resíduos de Praguicidas , Praguicidas , Humanos , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/química , Chá/química , Praguicidas/análise , Medição de Risco/métodos , Água
7.
Plant Foods Hum Nutr ; 78(1): 61-67, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36308615

RESUMO

Black tea is one of the six major tea categories and has a variety of bioactivities. However, little is known about its comprehensive evaluation of hypoglycemic effects and potential mechanisms. In this study, we investigated the in vivo hypoglycemic activity and potential mechanism for aqueous extracts of ordinary black tea (BT) and selenium-enriched black tea (Se-BT) by using an established high-fat diet together with streptozotocin (STZ)-induced hyperglycemic mouse model. Additionally, we also explored their α-glucosidase inhibition activity. The results show that both BT and Se-BT had a favorable glycosidase inhibitory activity. Moreover, the intervention of BT and Se-BT could regulate the mRNA expression and the level of serum parameters related to glucose and lipid metabolisms. Accordingly, they could activate the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling pathway and alleviate insulin resistance (IR) and hyperglycemia. Moreover, supplementation of BT and Se-BT increased the richness and diversity of intestinal flora and altered the abundance of beneficial and harmful bacteria. Both BT and Se-BT could regulate glucose metabolism, alleviate tissue damage, and restore intestinal flora dysbiosis, suggesting that they could be used as a natural functional food for preventing hyperglycemia.


Assuntos
Camellia sinensis , Microbioma Gastrointestinal , Hiperglicemia , Selênio , Animais , Camundongos , Glucose , Chá , Camundongos Obesos , Glicemia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hipoglicemiantes/farmacologia , Camellia sinensis/metabolismo , Lipídeos
8.
Anal Chem ; 94(22): 7936-7943, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35608073

RESUMO

Drug abuse is seriously endangering human health and jeopardizing society. There is an urgent need for rapid, sensitive, portable, and easy-to-operate methods for the daily detection of drugs in biological matrices. However, current drug detection methods based on chromatography, spectroscopy, immunosorbent assays, etc. are limited by the requirements of high logistical instruments and laboratory. Herein, we proposed a wearable electrochemical aptasensor with high sensitivity and specificity for the direct capture and rapid detection of multiple drugs in sweat. The single aptamer and dual aptamers with different base compositions were designed to compose the aptasensor array. Molecular docking simulations demonstrated different binding affinities between bioamines and aptamers. The developed aptasensor array is shown to be sufficient to generate distinct electrochemical fingerprints for different psychoactive drugs and interfering substances by extracting variable features from electrochemical signals. Sixteen analytes in the same concentration or gradient concentrations were identified with 100% accuracy. In addition, the wearable sensor platform was demonstrated to discriminate various drugs with similar chemical structures in artificial sweat and human sweat samples. The sensor array not only provided a new rapid method for the detection of drugs but also served as a reference for developing wearable sensors for onsite and daily testing of human biochemical information.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Aptâmeros de Nucleotídeos/química , Bioensaio , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Simulação de Acoplamento Molecular , Suor/química
9.
Appl Opt ; 61(31): 9279-9295, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607064

RESUMO

Near-space airships are high-end airships that are being vigorously developed in the aerospace industry. It has important application value in the telecommunication, surveillance, monitoring, remote sensing, and exploration fields. The envelope is the key component that provides lift to the airship. Online monitoring of envelope status is critical to ensuring airship performance, safety, and reliability. However, online monitoring of the 3D shape and strain of the airship envelope is still a challenging task. A hybrid multi-core and single-core fiber-optic monitoring method with a temperature self-compensation function is proposed to address this issue. The method uses multi-core fiber optic sensors, 3D curves, and a surface reconstruction algorithm to obtain the 3D shape of the envelope. Temperature decoupling of the sensing signal is carried out via sensors on the central core of the multi-core fibers that are only sensitive to temperature, thereby eliminating the influence of temperature changes on the measurement accuracy. The strain field of the envelope skin is measured by single-core fiber optic sensors and a strain interpolation algorithm. The accuracy of the proposed method is experimentally validated. The results show that the 3D shape measurement error of the envelope skin is 4.82% when the skin is bent in the range of 10m -1-15.38m -1. When the ambient temperature changes in the range of -50∘ C-150∘ C, the position measurement error caused by the temperature change is only 1.2% of the effective measurement length (160 mm) of the multi-core fiber optic sensor. When the skin is stretched in the range of 500-5000µÎµ, the measurement error of the average value of the skin strain field is only 0.75%. This proves that the proposed method can simultaneously measure the 3D shape and strain field of the envelope skin and also effectively suppress the influence of ambient temperature changes on the measurement accuracy. The proposed method has application prospects in the online monitoring of airship envelopes.

10.
Plant Foods Hum Nutr ; 77(2): 258-264, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35612700

RESUMO

Various functional components in tea have been well developed, but less research has been explored on glycoproteins in tea. In this paper, three types of glycoprotein fractions, namely tea selenium-binding glycoprotein1-1 (TSBGP1-1), TSBGP2-1, and TSBGP3-1, respectively, were extracted and purified from selenium-enriched coarse green tea. Chemical analysis revealed that three fractions were glycoproteins, but their selenium content, molecular weight, and monosaccharide composition were significantly different. Fourier transforms infrared (FT-IR) analysis indicated that three fractions contained characteristic absorption peaks of glycoproteins but differed in secondary structural composition. Thermogravimetric (TG) analysis showed that the thermal stability of the three fractions was dramatically distinct. The in vitro hypoglycemic activity showed that TSBGPs significantly activated the insulin receptor substrate 2 (IRS2)/protein kinase B (Akt) pathway in LO2 cells, then enhanced glucose metabolism and inhibited gluconeogenesis, and finally ameliorated insulin resistance (IR) and glucose metabolism disorders. Furthermore, Pearson correlation analysis reveals that the hypoglycemic activity was significantly correlated with Se, protein, monosaccharide composition (especially glucose), molecular weight, and secondary structure. Our results show that Se-enriched tea glycoprotein is a desirable candidate for developing anti-diabetic food, and TSBGP-2 and TSBGP-3 had a better regulation effect. Our results can provide a research reference for the extraction, physicochemical property, and function of selenium-enriched plant glycoproteins.


Assuntos
Selênio , Glicoproteínas , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Monossacarídeos/análise , Selênio/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Chá/química
11.
J Sci Food Agric ; 101(15): 6563-6577, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34018615

RESUMO

BACKGROUND: Dark tea, comprising one of the six major teas, has many biological activities, which originate from their active substrates, such as polyphenols, polysaccharides, and so on. The hypoglycemic effect is one of its most prominent activities, although less is known about their evaluation and potential role in the hypoglycemic mechanism. RESULTS: In the present study, we separately analyzed the phytochemical composition, glycosidase inhibition and free radical scavenging activities, and hypoglycemic activity in type 2 diabetes mellitus mice, as well as the alleviation of insulin resistance in HepG2 cells of four dark tea aqueous extracts. The results showed that the phytochemical composition of dark tea aqueous extracts was significantly different, and they all had good glycosidase inhibition and free radical scavenging activities, in vivo hypoglycemic activity and alleviation of insulin resistance, and could also activate the phosphatidylinositol 3-kinase-Akt-perixisome proliferation-activated receptor cascade signaling pathway to regulate glucose and lipid metabolism, change the key enzyme activities related to glucose metabolism and antioxidant activity, and reduce oxidative stress and inflammatory factor levels. Among them, Liubao brick tea (LBT) and Pu-erh tea (PET) possessed better glycosidase inhibitory activity, in vivo hypoglycemic activity and improved insulin resistance activity, whereas Qingzhuan brick tea and Fuzhuan brick tea had better free radical scavenging activity, which may be explained by their distinct phytochemical compositions, such as tea proteins, polysaccharides, polyphenols, catechins, and tea pigments and some elements. CONCLUSION: Dark tea is a highly attractive candidate for developing antidiabetic food, LBT and PET may be good natural sources of agricultural products with anti-diabetic effects. © 2021 Society of Chemical Industry.


Assuntos
Glicemia/metabolismo , Camellia sinensis/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Hipoglicemiantes/metabolismo , Resistência à Insulina , Fígado/metabolismo , Compostos Fitoquímicos/metabolismo , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Camellia sinensis/química , China , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Células Hep G2 , Humanos , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Chá
12.
Glycoconj J ; 37(2): 241-250, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31915970

RESUMO

Coarse tea is made of mature tea plant (Camellia sinensis L.) shoots and is generally discarded as a worthless crop product, but has been proved an excellent material for the treatment of diabetes. This study aims to evaluate the effects of the extraction techniques WE (water extraction), UAE (ultrasound-assisted extraction), MAE (microwave-assisted extraction), and EE (enzyme extraction) on the physicochemical properties and antidiabetic activities of polysaccharides from coarse tea (CTPSs). The results showed that all four CTPSs had homogeneity in the monosaccharide types and similar IR (Infrared spectroscopy) characteristic absorption peaks, but differed in monosaccharide proportion and molecular weight distribution. Compared with the other three extraction techniques, CCTPS extracted by EE had the lowest protein content, the highest total sugar content of 71.83% and a polysaccharide yield of 4.52%. In addition, EE-CTPS had the best hypoglycemic activity that was better than ordinary green tea polysaccharides, the α-glucosidase and α-amylase inhibitory activities of EE-CTPS were highest in the range of 2-10 mg/mL compared with the other three CTPSs, which may be related to its smaller molecular weight and porous structure. The results suggested that the EE method was a good way to extract polysaccharides from coarse tea for food and pharmaceutical production.


Assuntos
Fracionamento Químico/métodos , Inibidores Enzimáticos/análise , Hipoglicemiantes/análise , Polissacarídeos/análise , Chá/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucosidases/antagonistas & inibidores , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Micro-Ondas , Polissacarídeos/química , Polissacarídeos/farmacologia , Ondas Ultrassônicas , alfa-Amilases/antagonistas & inibidores
13.
J Org Chem ; 85(5): 3902-3910, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31944121

RESUMO

A convenient and straightforward strategy for the synthesis of 2,3-disubstituted and 2,3,5-trisubstituted furans via a base-promoted domino reaction of ß-keto compounds with vinyl dichlorides is described. This transition-metal-free approach proceeds under operationally simple reaction conditions featuring easily available starting materials, a broad substrate scope, and good functional group tolerance.

14.
J Am Chem Soc ; 141(39): 15626-15633, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31532665

RESUMO

Organophosphonate-based nerve agents, such as VX, Sarin (GB), and Soman (GD), are among the most toxic chemicals to humankind. Recently, we have shown that Zr-based metal-organic frameworks (Zr-MOFs) can effectively catalyze the hydrolysis of these toxic chemicals for diminishing their toxicity. On the other hand, utilizing these materials in powder form is not practical, and developing scalable and economical processes for integrating these materials onto fibers is crucial for protective gear. Herein, we report a scalable, template-free, and aqueous solution-based synthesis strategy for the production of Zr-MOF-coated textiles. Among all MOF/fiber composites reported to date, the MOF-808/polyester fibers exhibit the highest rates of nerve agent hydrolysis. Moreover, such highly porous fiber composites display significantly higher protection time compared to that of its parent fabric for a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES). A decreased diffusion rate of toxic chemicals through the MOF layer can provide time needed for the destruction of the harmful species.

15.
Org Biomol Chem ; 17(18): 4564-4571, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994641

RESUMO

An N-heterocyclic carbene (NHC)-catalyzed α-functionalization of the in situ activated α,ß-unsaturated carboxylic acids bearing γ-H was realized through formal [4 + 2] annulations with o-quinone methides, which paved a new avenue for the assembly and modification of the dihydrocoumarin scaffold in good yields with excellent diastereo- and enantioselectivities.

16.
Anal Chem ; 90(11): 6371-6375, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29775042

RESUMO

Benefiting from the integrated functions of cilia and glomeruli in the olfactory system, animals can discriminate various odors even in hostile environments. Inspired by this synergetic system of response and signal processing units, a sensor chip of graphene oxide (GO) and photonic crystals (PCs) is fabricated. The GO aerogel functions like the olfactory cilia, which effectively captures the analytes and generates abundant sensing signals for recognition; and the PCs act as the olfactory glomeruli, whose periodic structure enables selective enhancement of the fluorescent signals to realize further signal processing. Ten biogenic amines and seven drug amines are effectively discriminated. The integrated sensor strategy of response and signal manipulation units will promote enormous pursuits of rapid clinical diagnosis or intractable pathology analysis.


Assuntos
Aminas Biogênicas/análise , Materiais Biomiméticos/química , Técnicas Biossensoriais/instrumentação , Transferência Ressonante de Energia de Fluorescência/instrumentação , Grafite/química , Preparações Farmacêuticas/análise , Desenho de Equipamento , Corantes Fluorescentes/análise , Fótons
17.
J Org Chem ; 82(3): 1790-1795, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28074651

RESUMO

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] synthesis of dihydrocoumarins was realized from saturated carboxylic acids and o-quinone methides via an in situ activation strategy. This protocol results in excellent diastereoselectivity and enantioselectivity and good yields and uses readily available and inexpensive starting materials.

18.
Nature ; 507(7491): 169, 2014 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-24622192
20.
Front Genet ; 15: 1331751, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100075

RESUMO

Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus. Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis. Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03-1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01-1.54). Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated.

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