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1.
Eur J Med Chem ; 268: 116272, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402749

RESUMO

Acute lung injury (ALI) is a serious public health problem associated with high morbidity and mortality. However, few efficacious drugs are clinically available. Inhibition of proinflammatory cytokines is considered to be a promising method for the treatment of inflammatory diseases. Herein, the total synthesis of a dibenzylbutane lignan, 9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (LCA), was completed. A series of LCA derivatives were designed and synthesized, and their anti-inflammatory activities were evaluated. Derivative 14r significantly inhibited LPS-induced expression of NO and the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in RAW 264.7 cells and inhibited activation of the NF-κB pathway. Compound 14r reduced LPS-induced pulmonary inflammation and ALI in mice. It showed significant protective effects against LPS-induced ALI in mice and significantly reduced levels of proinflammatory cytokines in serum and bronchoalveolar lavage fluid. The ratio of wet weight to dry weight of lung tissue was normalized by compound 14r, which was consistent with suppression of neutrophil infiltration and production of proinflammatory cytokines. Compound 14r reduced the mRNA expression of some proinflammatory cytokines, improved histopathologic changes, and reduced macrophage infiltration in lung tissues. Collectively, these results suggest a new series of LCA derivatives that could be promising anti-inflammatory agents for ALI treatment.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , NF-kappa B/metabolismo , Citocinas/metabolismo
2.
J Sep Sci ; 47(2): e2300802, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38286730

RESUMO

Polyethylene glycol (PEG) is one of the most commonly used polymers in drug delivery systems. The investigation of the pharmacokinetic behavior of PEG is important for revealing the toxicity and efficiency of PEG-related Nano-drug delivery systems. A high through-put and selective ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method coupled with collision-induced dissociation (CID) in source technique was developed and validated to determine PEG1K polymers in cellular samples in this study. The countless precursor ions of PEG1K are dissociated in the source to generate numerous product ions which have different numbers of subunits. The transition of [M+H]+ precursor ions → product ions at m/z 177.1 (four subunits)→89.1 (two subunits) was selected to determine PEG1K due to its high sensitivity. The UHPLC-MS/MS method coupled with CID in the source showed good linearity over the range of 0.1-10 µg/mL. Intra-day and inter-day accuracies and precisions of the assay were all within ± 12.39%. The assay was successfully applied to a cellular pharmacokinetic study of PEG1K in human breast cancer cells. The cytotoxicity of PEG1K polymers was also studied and the results indicated that the cytotoxicity of PEG1K was not significant in the range of 5-1200 µg/mL.


Assuntos
Polímeros , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Polímeros/toxicidade , Polímeros/análise , Polietilenoglicóis/química , Íons
3.
Acta Pharm Sin B ; 14(1): 405-420, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38261810

RESUMO

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

4.
BMC Plant Biol ; 23(1): 659, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124039

RESUMO

BACKGROUND: German chamomile (Matricaria chamomilla L.) is an important medicinal plant, and the essential oils in the flowers have various biological activities. Genetic transformation systems are important for plant quality improvement and molecular research. To the best of our knowledge, a genetic transformation system has not yet been reported for German chamomile. RESULTS: In this study, we developed Agrobacterium-mediated transformation protocols for German chamomile callus tissues. This involved optimizing key parameters, such as hygromycin and cefotaxime concentrations, bacterial density, and infection and co-culture durations. We also performed gas chromatography-mass spectrometry analysis to identify volatile compounds in non-transgenic and transgenic callus and hairy root tissues. Furthermore, to compare and verify the callus transformation system of German chamomile, we transferred McFPS to the hairy roots of German chamomile. The results showed that the optimal conditions for Agrobacterium-mediated callus tissue transformation were as follows: explant, petiole; cefotaxime concentration, 300 mg/L; hygromycin concentration, 10 mg/L; and bacterial solution concentration, OD600 = 0.6; callus transformation efficiency was the highest when the co-culture time was 3 days. CONCLUSIONS: Establishment of a high-efficiency callus transformation system will lay the foundation for gene function identification in German chamomile.


Assuntos
Matricaria , Óleos Voláteis , Matricaria/genética , Matricaria/química , Óleos Voláteis/análise , Cinamatos , Cefotaxima , Camomila/genética , Camomila/química
5.
J Neuropathol Exp Neurol ; 82(9): 774-786, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37533277

RESUMO

Diabetic encephalopathy is a common complication of type 1 diabetes. However, there have been few studies on cognitive impairment and hippocampal damage in type 1 diabetes mellitus (T1DM) using dogs as experimental animals. To investigate the effects of diabetes on the CNS, 40 adult beagles were divided into streptozotocin/alloxan type 1 diabetes model and control groups. The duration of diabetes in the model group was 120 days. A cognitive dysfunction scale was used to assess cognitive function. Hematoxylin and eosin and Golgi-Cox staining methods were used to observe morphological damage to the hippocampus. Transcriptomics was used to investigate differential gene expression in the hippocampus. The results showed that the cognitive dysfunction score of the model group was significantly higher than that of the control group. In addition, the number of normal neurons, the complexity of dendritic morphology, and the density of dendritic spines were decreased in the hippocampus of diabetic dogs. A total of 672 differentially expressed genes (DEGs) were identified, 289 of which were upregulated, and 383 were downregulated. Modified genes included DBH, IGFBP2, AVPR1A, and DRAXIN. In conclusion, type 1 diabetic dogs exhibit cognitive dysfunction. The DEGs were mainly enriched in metabolic, PI3K-Akt signaling, and neuroactive ligand-receptor interaction pathways.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animais , Cães , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Diabetes Mellitus Experimental/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Perfilação da Expressão Gênica , Hipocampo/metabolismo
6.
PLoS Pathog ; 19(4): e1011305, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37053288

RESUMO

N6-methyladenosine (m6A) modification on viral RNAs has a profound impact on infectivity. m6A is also a highly pervasive modification for influenza viral RNAs. However, its role in virus mRNA splicing is largely unknown. Here, we identify the m6A reader protein YTHDC1 as a host factor that associates with influenza A virus NS1 protein and modulates viral mRNA splicing. YTHDC1 levels are enhanced by IAV infection. We demonstrate that YTHDC1 inhibits NS splicing by binding to an NS 3' splicing site and promotes IAV replication and pathogenicity in vitro and in vivo. Our results provide a mechanistic understanding of IAV-host interactions, a potential therapeutic target for blocking influenza virus infection, and a new avenue for the development of attenuated vaccines.


Assuntos
Vírus da Influenza A , Influenza Humana , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/metabolismo , Influenza Humana/genética , Replicação Viral/genética , RNA Mensageiro/genética , Fatores de Processamento de RNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo
7.
Gels ; 9(2)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36826321

RESUMO

Development of low-cost, high-temperature-resistant and salt-resistant fracturing fluids is a hot and difficult issue in reservoir fluids modification. In this study, an organic zirconium crosslinker that was synthesized and crosslinked with partially hydrolyzed polyacrylamide (HPAM) was employed as a cost-effective polymer thickener to synthesize a high-temperature-resistant and salt-resistant fracturing fluid. The rheological properties of HPAM in tap water solutions and 2 × 104 mg/L salt solutions were analyzed. The results demonstrated that addition of salt reduced viscosity and viscoelasticity of HPAM solutions. Molecular dynamics (MD) simulation results indicated that, due to electrostatic interaction, the carboxylate ions of HPAM formed an ionic bridge with metal cations, curling the conformation, decreasing the radius of rotation and thus decreasing viscosity. However, optimizing fracturing fluids formulation can mitigate the detrimental effects of salt on HPAM. The rheological characteristics of the HPAM fracturing fluid crosslinking process were analyzed and a crosslinking rheological kinetic equation was established under small-amplitude oscillatory shear (SAOS) test. The results of a large-amplitude oscillation shear (LAOS) test indicate that the heating effect on crosslinking is stronger than the shear effect on crosslinking. High-temperature-resistant and shear-resistant experiments demonstrated good performance of fracturing fluids of tap water and salt solution at 200 °C and 180 °C.

8.
Int J Mol Sci ; 24(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36675248

RESUMO

The essential oil of German chamomile (Matricaria recutita L.) is widely used in food, cosmetics, and the pharmaceutical industry. α-Bisabolol is the main active substance in German chamomile. Farnesyl diphosphate synthase (FPS) and α-bisabolol synthase (BBS) are key enzymes related to the α-bisabolol biosynthesis pathway. However, little is known about the α-bisabolol biosynthesis pathway in German chamomile, especially the transcription factors (TFs) related to the regulation of α-bisabolol synthesis. In this study, we identified MrFPS and MrBBS and investigated their functions by prokaryotic expression and expression in hairy root cells of German chamomile. The results suggest that MrFPS is the key enzyme in the production of sesquiterpenoids, and MrBBS catalyzes the reaction that produces α-bisabolol. Subcellular localization analysis showed that both MrFPS and MrBBS proteins were located in the cytosol. The expression levels of both MrFPS and MrBBS were highest in the extension period of ray florets. Furthermore, we cloned and analyzed the promoters of MrFPS and MrBBS. A large number of cis-acting elements related to light responsiveness, hormone response elements, and cis-regulatory elements that serve as putative binding sites for specific TFs in response to various biotic and abiotic stresses were identified. We identified and studied TFs related to MrFPS and MrBBS, including WRKY, AP2, and MYB. Our findings reveal the biosynthesis and regulation of α-bisabolol in German chamomile and provide novel insights for the production of α-bisabolol using synthetic biology methods.


Assuntos
Matricaria , Óleos Voláteis , Sesquiterpenos , Geraniltranstransferase/genética , Matricaria/química , Fatores de Transcrição/genética , Óleos Voláteis/química , Sesquiterpenos/química
9.
Trends Plant Sci ; 28(4): 460-470, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36473772

RESUMO

Proteins are the most frequently used biocatalysts, and their structures determine their functions. Modifying the functions of proteins on the basis of their structures lies at the heart of protein engineering, opening a new horizon for metabolic engineering by efficiently generating stable enzymes. Many attempts at classical metabolic engineering have focused on improving specific metabolic fluxes and producing more valuable natural products by increasing gene expression levels and enzyme concentrations. However, most naturally occurring enzymes show limitations, and such limitations have hindered practical applications. Here we review recent advances in protein engineering in synthetic biology, chemoenzymatic synthesis, and plant metabolic engineering and describe opportunities for designing and constructing novel enzymes or proteins with desirable properties to obtain more active natural products.


Assuntos
Produtos Biológicos , Engenharia de Proteínas , Engenharia Metabólica , Plantas/genética , Biologia Sintética
10.
Plant Biotechnol J ; 21(3): 591-605, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36478140

RESUMO

MicroRNAs (miRNAs) play crucial roles in plant development and secondary metabolism through different modes of sequence-specific interaction with their targets. Artemisinin biosynthesis is extensively regulated by phytohormones. However, the function of phytohormone-responsive miRNAs in artemisinin biosynthesis remains enigmatic. Thus, we combined the analysis of transcriptomics, small RNAs, and the degradome to generate a comprehensive resource for identifying key miRNA-target circuits involved in the phytohormone-induced process of artemisinin biosynthesis in Artemisia annua. In total, 151 conserved and 52 novel miRNAs and their 4132 targets were determined. Based on the differential expression analysis, miR160 was selected as a potential miRNA involved in artemisinin synthesis. Overexpressing MIR160 significantly impaired glandular trichome formation and suppressed artemisinin biosynthesis in A. annua, while repressing its expression resulted in the opposite effect, indicating that miR160 negatively regulates glandular trichome development and artemisinin biosynthesis. RNA ligase-mediated 5' RACE and transient transformation assays showed that miR160 mediates the RNA cleavage of Auxin Response Factor 1 (ARF1) in A. annua. Furthermore, ARF1 was shown to increase artemisinin synthesis by activating AaDBR2 expression. Taken together, our results reveal the intrinsic link between the miR160-ARF1 module and artemisinin biosynthesis, and may expedite the innovation of metabolic engineering approaches for high and stable production of artemisinin in the future.


Assuntos
Artemisia annua , Artemisininas , MicroRNAs , Reguladores de Crescimento de Plantas/metabolismo , Tricomas/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Ácidos Indolacéticos/metabolismo , MicroRNAs/metabolismo , Artemisininas/metabolismo , Artemisininas/farmacologia , Proteínas de Plantas/genética
12.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456945

RESUMO

Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV-host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease.


Assuntos
Vírus da Influenza A , Influenza Humana , Humanos , Vírus da Influenza A/metabolismo , Carioferinas/metabolismo , Proteínas Virais/metabolismo , Replicação Viral , beta Carioferinas/metabolismo
13.
Atherosclerosis ; 349: 204-210, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35450749

RESUMO

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) have high residual risk of cardiovascular events, whether the residual risk is associated with elevated level of lipoprotein(a) [Lp(a)] is unascertained. We aimed to explore the impact of Lp(a) levels on the risk of major adverse clinical events (MACEs) in CKD patients hospitalized for acute coronary syndrome (ACS) compared to those without CKD. METHODS: The data of patients hospitalized for ACS were collected at the China-Japan Friendship Hospital from January 2015 to December 2019. Patients were divided into 2 groups according to renal function: non-CKD group (eGFR≥60 ml/min/1.73 m2) and CKD group (eGFR <60 ml/min/1.73 m2). Multivariate Cox regression analysis and restricted cubic splines were performed to explore the relationship between Lp(a) levels and MACEs. RESULTS: A total of 1306 patients were enrolled. Patients with CKD had higher Lp(a) concentrations compared with those without CKD. During a median follow-up of 3.9 years, an elevated Lp(a) value was an independent predictor for MACEs in the overall population. Patients with a high Lp(a) level had higher risk of MACEs than those with a low Lp(a) level, regardless of renal function. The association between higher Lp(a) levels and MACEs remained consistent using the cut-off value of median (11.57 mg/dL), 30 mg/dL and 50 mg/dL in patients with CKD. On the contrary, Lp(a) higher than 50 mg/dL was associated with significantly higher risk of MACEs in patients without CKD. CONCLUSIONS: We confirmed that a high Lp(a) level was associated with long term adverse outcomes in ASC patients, especially in those with CKD.


Assuntos
Síndrome Coronariana Aguda , Insuficiência Renal Crônica , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Progressão da Doença , Humanos , Lipoproteína(a) , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco
14.
Appl Opt ; 61(8): 2089-2095, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35297900

RESUMO

Traditional electrical expendable bathythermograph (XBT) is designed to fall at a known rate based on a great deal of experiments so that the depth of the temperature profile can be inferred from the time it enters the water. Unlike the traditional electrical XBT, which derives the depth from fall-rate equations, we propose an all-optical fiber (AOF) XBT (AOF-XBT) based on cascade of two fiber Bragg gratings (FBGs). In the AOF-XBT, the depth data comes from one FBG, which responds in real time to the pressure acting on the diaphragm, and temperature data can be measured via the other FBG simultaneously. First, the pressure and temperature response characteristics of the AOF-XBT are analyzed based on a finite element method. Then, the temperature and pressure calibrations for the AOF-XBT is completed after they are packaged. Results show that the mean-temperature sensitivity of two sensors are 14.765 and 13.705 pm/°C in the range of 5°C-30°C, and the mean-pressure sensitivities are -2.75586 and -3.00472nm/MPa in the range of 0-0.6 MPa, respectively. At last, by comparing the results obtained from the AOF-XBT and the SBE 911plus CTD that tested in the sea area of Weihai, the trends of the temperature-depth profile from the two devices are consistent, which presents a new all-optical technique to provide full ocean temperature-depth profile observations.

15.
Plant J ; 108(5): 1365-1381, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34585814

RESUMO

Whole genome duplication (WGD) in plants is typically followed by genomic downsizing, where large portions of the new genome are lost. Whether this downsizing is accompanied by increased or decreased evolutionary rates of the remaining genes is poorly known, not least because homeolog pairings are often obscured by chromosomal rearrangement. Here, we use the newly published genome from a sedge, namely Kobresia littledalei, and CRISPR/Cas-9 editing to investigate how the Rho WGD event 70 million years ago (MYA) affected transcription factor evolutionary rates, fates, and function in rice (Oryza sativa) and sorghum (Sorghum bicolor). We focus on the 30-member DNA-binding with one zinc finger (Dof) transcription factor family in both crops due to their agronomic importance. Using the known speciation dates of rice from Kobresia (97 MYA) and sorghum (50 MYA), we find that rates of amino acid substitution in the critical Dof domain region were over twofold higher during the 20-million-year period following the WGD than before or afterward. Through comparison of synteny blocks, we report that at least 11% of Dof genes were purged from 70 to 50 MYA, while only 6% have been lost in the most recent 50-million-year interval. CRISPR/Cas9 editing revealed widespread fitness-related defects in flowering and lack of redundancy of paired members, as well as significant differences in expression between gene pairs. Together these findings demonstrate the strength of Dof genes as a model for deep evolutionary study and offer one of the most detailed portraits yet of the Rho WGD impact on a gene lineage.


Assuntos
Genoma de Planta/genética , Oryza/genética , Proteínas de Plantas/genética , Sorghum/genética , Evolução Biológica , Grão Comestível/genética , Evolução Molecular , Duplicação Gênica , Sintenia , Fatores de Transcrição/genética
16.
Front Cardiovasc Med ; 8: 720113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540919

RESUMO

Background: The value of aspirin for primary prevention continues to be debated. Data showing whether aspirin use for primary prevention adheres to established guidelines in real world practice are sparse. Methods: A total of 13,104 patients without cardiovascular diseases (CVD) were selected from the DYS-lipidemia International Study of China, a national survey of patients with dyslipidemia in 2012. The CVD risk of the participants were calculated using the 10-year risk of Ischemic Cardiovascular Diseases model. The misuse of aspirin for primary prevention was defined as having CVD risk <10% with daily aspirin. Multivariate logistic regression models were used to explore risk factors associated with aspirin misuse. Results: The proportion of the patients categorized as low, moderate and high risk for CVD were 52.9, 21.6, and 25.4% respectively. The misuse frequency of aspirin was 31.0% (2,147/6,933) in patients with low risk. The misuse of aspirin increased with aging for both men and women. In the multivariate analysis, the independent risk factors associated with aspirin misuse were hypertension, diabetes mellitus, a family history of premature CVD, and elderly age. Level of total cholesterol is negatively associated with aspirin misuse. Patients from low level hospitals are more likely to be taking aspirin inappropriately. Results remained consistent after including 2,837 patients having 10-year risk for CVD between 10 and <20%. Conclusion: The misuse of aspirin for primary prevention is common in patients having CVD risk <10%. There are important opportunities to improve evidence-based aspirin use for the primary prevention of CVD in Chinese patients. Clinical Trial Registration:https://clinicaltrials.gov/, identifier [NCT01732952].

17.
Clin Cardiol ; 44(6): 789-796, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33978269

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with acute coronary syndrome (ACS) and may potentially influence platelet function. HYPOTHESIS: We explored the influence of renal function on platelet reactivity to investigate whether high residual platelet reactivity (HRPR) is associated with cardiovascular events. METHODS: ACS patients treated with aspirin and clopidogrel were prospectively enrolled. Patients were categorized into two groups on the basis of baseline estimated glomerular filtration rate (eGFR): non-CKD (eGFR ≥60 mL/min/1.73 m2 ) and CKD (eGFR <60 mL/min/1.73 m2 ). Platelet function was measured by thromboelastography ≥5 days after maintenance dual antiplatelet therapy. Major adverse clinical events (MACEs) were collected at 1 year after discharge. RESULTS: There were 282 non-CKD patients and 212 CKD patients. A significant difference in median MAADP value was observed between the two groups (15.0 mm vs. 31.3 mm, p < .001). HRPR was more prevalent in the CKD group than the non-CKD group (27.4% vs 9.6%, p < .001). At 1-year follow-up, the incidence of MACEs was significantly higher for those with both CKD and HRPR compared with those with either CKD or HRPR (37.9% vs. 18.5%, p < .001). The relationship between HRPR and MACEs was consistent across CKD strata without evidence of interaction. Adding platelet reactivity to eGFR improved the model with area under the curve increasing from 0.703 to 0.734. CONCLUSION: In patients with ACS, the risk of HRPR increased with declining eGFR. Both CKD and HRPR were associated with MACEs at 1-year follow-up.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas , Clopidogrel , Humanos , Rim/fisiologia , Agregação Plaquetária , Inibidores da Agregação Plaquetária/efeitos adversos , Ticagrelor , Ticlopidina/efeitos adversos
18.
PLoS Biol ; 19(3): e3001164, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33750968

RESUMO

In contrast to common meiotic gene conversion, mitotic gene conversion, because it is so rare, is often ignored as a process influencing allelic diversity. We show that if there is a large enough number of premeiotic cell divisions, as seen in many organisms without early germline sequestration, such as plants, this is an unsafe position. From examination of 1.1 million rice plants, we determined that the rate of mitotic gene conversion events, per mitosis, is 2 orders of magnitude lower than the meiotic rate. However, owing to the large number of mitoses between zygote and gamete and because of long mitotic tract lengths, meiotic and mitotic gene conversion can be of approximately equivalent importance in terms of numbers of markers converted from zygote to gamete. This holds even if we assume a low number of premeiotic cell divisions (approximately 40) as witnessed in Arabidopsis. A low mitotic rate associated with long tracts is also seen in yeast, suggesting generality of results. For species with many mitoses between each meiotic event, mitotic gene conversion should not be overlooked.


Assuntos
Conversão Gênica/genética , Variação Genética/genética , Oryza/genética , Plantas/genética , Alelos , Conversão Gênica/fisiologia , Genótipo , Células Germinativas/metabolismo , Meiose/genética , Mitose/genética , Recombinação Genética/genética
19.
Front Nutr ; 8: 823803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35178419

RESUMO

Dendrobium catenatum polysaccharides (DCPs) have attracted attention due to their multiple physiological activities and health benefits. In this study, a novel water-soluble DCP was obtained from fresh D. catenatum stems through three-phase partitioning and ethanol precipitation at room temperature. Its structural characteristics, rheological property, and in vitro immunostimulatory activity were evaluated. Results demonstrated that DCP was a homogenous polysaccharide with a carbohydrate content of 92.75% and a weight-average molecular weight of 2.21 × 105 Da. This polysaccharide is an O-acetylated glucomannan comprised by glucose, mannose, and galacturonic acid in a molar ratio of 30.2:69.5:0.3 and mainly comprises (1→4)-ß-D-mannopyranosyl (Manp), 2-O-acetyl-(1→4)-ß-D-Manp, (1→6)-α-D-glucopyranosyl (Glcp), and (1→4)-α-D-Glcp residues. DCP exhibits an extended rigid chain in an aqueous solution and favorable steady shear fluid and dynamic viscoelastic behaviors. In vitro immunostimulating assays indicated that DCP activates RAW264.7 cells, thus markedly promoting macrophage proliferation and phagocytosis and increasing the levels of nitric oxide, interferon-γ, interleukin-6, and interleukin-1ß. Moreover, the presence of O-acetyl group and high M w in DCP might be responsible for its potent immunostimulatory activity in vitro. Therefore, our data suggested that DCP could be developed as a promising immunostimulant in functional food and pharmaceutical industries.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35010386

RESUMO

Successful aging is achieved throughout the life course, and successful aging groups tend to have good psychosocial and physical conditions and are active in social activities. With increasing age, the mental health problems of older adults have become increasingly prominent, and the choice of pension mode is closely related to the mental health of older adults. Starting from the psychological level of the older adult, this paper used data from the 2018 Chinese Longitudinal Healthy Longevity Survey to study the impact of three pension methods on the mental health of older adults. The study found that, at present, there are three types of pension modes in China: living alone, family pension, and institutional care, and family pensions are still the mainstream pension mode. Older adults with deeper negative feelings are more inclined to family pensions than to live alone, but the spiritual comfort provided by family members does not improve the negative feelings of older adults. Institutional care deepens the negative feeling and reduces the positive feeling of older adults. In addition, retirement or pension and medical insurance, as life security in old age, can effectively reduce the negative feelings of old age and promote positive feelings. In view of the present situation of China's pension mode and the psychological characteristics of the older adults, we should further build a perfect family pension security system, promote the personalized service construction of older adult care institutions, promote applicable aging renovation of existing residential areas, and encourage older adults to engage in healthy exercise.


Assuntos
Saúde Mental , Pensões , China , Ambiente Domiciliar , Aposentadoria
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