RESUMO
Salt stress is one of the major factors limiting plant growth and productivity. Many studies have shown that serine hydroxymethyltransferase (SHMT) gene play an important role in growth, development and stress response in plants. However, to date, there have been few studies on whether SHMT3 can enhance salt tolerance in plants. Therefore, the effects of overexpression or silencing of CsSHMT3 gene on cucumber seedling growth under salt stress were investigated in this study. The results showed that overexpression of CsSHMT3 gene in cucumber seedlings resulted in a significant increase in chlorophyll content, photosynthetic rate and proline (Pro) content, and antioxidant enzyme activity under salt stress condition; whereas the content of malondialdehyde (MDA), superoxide anion (H2O2), hydrogen peroxide (O2·-) and relative conductivity were significantly decreased when CsSHMT3 gene was overexpressed. However, the content of chlorophyll and Pro, photosynthetic rate, and antioxidant enzyme activity of the silenced CsSHMT3 gene lines under salt stress were significantly reduced, while MDA, H2O2, O2·- content and relative conductivity showed higher level in the silenced CsSHMT3 gene lines. It was further found that the expression of stress-related genes SOD, CAT, SOS1, SOS2, NHX, and HKT was significantly up-regulated by overexpressing CsSHMT3 gene in cucumber seedlings; while stress-related gene expression showed significant decrease in silenced CsSHMT3 gene seedlings under salt stress. This suggests that overexpression of CsSHMT3 gene increased the salt tolerance of cucumber seedlings, while silencing of CsSHMT3 gene decreased the salt tolerance. In conclusion, CsSHMT3 gene might positively regulate salt stress tolerance in cucumber and be involved in regulating antioxidant activity, osmotic adjustment, and photosynthesis under salt stress. KEY MESSAGE: CsSHMT3 gene may positively regulate the expression of osmotic system, photosynthesis, antioxidant system and stress-related genes in cucumber.
Assuntos
Clorofila , Cucumis sativus , Regulação da Expressão Gênica de Plantas , Fotossíntese , Estresse Salino , Tolerância ao Sal , Plântula , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/fisiologia , Cucumis sativus/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Tolerância ao Sal/genética , Estresse Salino/genética , Clorofila/metabolismo , Fotossíntese/genética , Fotossíntese/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glicina Hidroximetiltransferase/genética , Glicina Hidroximetiltransferase/metabolismo , Antioxidantes/metabolismo , Malondialdeído/metabolismo , Plantas Geneticamente Modificadas , Inativação GênicaRESUMO
PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.
Assuntos
Estado Terminal , Unidades de Terapia Intensiva , Infarto do Miocárdio , Readmissão do Paciente , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/epidemiologia , Masculino , Feminino , Readmissão do Paciente/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos de Coortes , Tempo de Internação/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Fatores de RiscoRESUMO
In tomato (Solanum lycopersicum), the ripening of fruit is regulated by the selective expression of ripening-related genes, and this procedure is controlled by transcription factors (TFs). In the various plant-specific TF families, the no apical meristem (NAM), Arabidopsis thaliana activating factor 1/2 (ATAF1/2), and cup-shaped cotyledon 2 (CUC2; NAC) TF family stands out and plays a significant function in plant physiological activities, such as fruit ripening (FR). Despite the numerous genes of NAC found in the tomato genome, limited information is available on the effects of NAC members on FR, and there is also a lack of studies on their target genes. In this research, we focus on SlNAP1, which is a NAC TF that positively influences the FR of tomato. By employing CRISPR/Cas9 technology, compared with the wild type (WT), we generated slnap1 mutants and observed a delay in the ethylene production and color change of fruits. We employed the yeast one-hybrid (Y1H) and dual-luciferase reporter (DLR) assays to confirm that SlNAP1 directly binds to the promoters of two crucial genes involved in gibberellin (GA) degradation, namely SlGA2ox1 and SlGA2ox5, thus activating their expression. Furthermore, through a yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BIFC) and luciferase (LUC) assays, we established an interaction between SlNAP1 and SlGID1. Hence, our findings suggest that SlNAP1 regulates FR positively by activating the GA degradation genes directly. Additionally, the interaction between SlNAP1 and SlGID1 may play a role in SlNAP1-induced FR. Overall, our study provides important insights into the molecular mechanisms through which NAC TFs regulate tomato FR via the GA pathway.
Assuntos
Frutas , Regulação da Expressão Gênica de Plantas , Giberelinas , Proteínas de Plantas , Solanum lycopersicum , Fatores de Transcrição , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Giberelinas/metabolismo , Regiões Promotoras Genéticas/genética , Etilenos/metabolismoRESUMO
This study utilizes network pharmacology analysis to investigate the components, targets, and pathways involved in the treatment of chronic heart failure (CHF) with the combination of "Astragali Radix-Cassia Twig-Poria." The TCMSP, GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases were utilized to identify the active ingredients and targets of this combination for CHF. Protein interactions were derived from the STRING database, and Cytoscape was used to construct the "drug-component-target-disease" network and protein interactions network. The GO function and KEGG signaling pathway were enriched, and molecular docking was performed to verify the stability of the core components and their targets. The study identified 41 active ingredients, 101 targets (including 94 related to CHF), 9 core targets, and 26 core ingredients of "Astragali Radix-Cassia Twig-Poria." Additionally, 1444 GO entries and 140 KEGG pathways (including 36 related to CHF) were found. Molecular docking results confirmed the binding ability of the combination to core targets. Overall, this study provides valuable insights into the key components, targets, and pathways involved in the treatment of CHF with "Astragali Radix-Cassia Twig-Poria," contributing to further research on its pharmacological effects.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Simulação de Acoplamento Molecular , Farmacologia em Rede , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Crônica/tratamento farmacológico , Astrágalo/química , Mapas de Interação de Proteínas/efeitos dos fármacosRESUMO
Cordyceps javanica has been registered as a fungal insecticide in several countries. However, little is known about whether metabolic toxins are involved in the insecticidal process. In this research, we assessed the insecticidal activity of the fermentation broth of C. javanica. Myzus persicae mortality differed when exposed to the metabolized C. javanica broths at 3 days post fermentation (DPF) and 5 DPF. Comparison of the metabolic fluid at 3 DPF and 5 DPF revealed a key alkaloid, heteratisine, which was found to have insecticidal activity and acetylcholinesterase (AChE) inhibitory activity. Heteratisine has high insecticidal activity against adult M. persicae, the absolute 50% lethal concentration (LC50) was only 0.2272 mg/L. Heteratisine showed high inhibitory activity on AChE with the 50% maximal inhibitory concentration (IC50) of 76.69 µM. Molecular docking and dynamic simulations showed that heteratisine conjugation occurs at the peripheral anionic site (PAS) of the AChE of M. persicae, leading to suppression of enzyme activity. Heteratisine was rarely found in fungal metabolites, which helps us to understand the complex and elaborate insecticidal mechanism of C. javanica.
Assuntos
Acetilcolinesterase , Afídeos , Inibidores da Colinesterase , Cordyceps , Inseticidas , Simulação de Acoplamento Molecular , Cordyceps/metabolismo , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/metabolismo , Inseticidas/toxicidade , Animais , Afídeos/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/toxicidade , Acetilcolinesterase/metabolismo , Alcaloides/química , Metabolismo SecundárioRESUMO
A motor imagery brain-computer interface connects the human brain and computers via electroencephalography (EEG). However, individual differences in the frequency ranges of brain activity during motor imagery tasks pose a challenge, limiting the manual feature extraction for motor imagery classification. To extract features that match specific subjects, we proposed a novel motor imagery classification model using distinctive feature fusion with adaptive structural LASSO. Specifically, we extracted spatial domain features from overlapping and multi-scale sub-bands of EEG signals and mined discriminative features by fusing the task relevance of features with spatial information into the adaptive LASSO-based feature selection. We evaluated the proposed model on public motor imagery EEG datasets, demonstrating that the model has excellent performance. Meanwhile, ablation studies and feature selection visualization of the proposed model further verified the great potential of EEG analysis.
Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Processamento de Sinais Assistido por Computador , Eletroencefalografia/métodos , Humanos , Algoritmos , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Imaginação/fisiologiaRESUMO
BACKGROUND: Methane (CH4) and brassinosteroids (BRs) are important signaling molecules involved in a variety of biological processes in plants. RESULTS: Here, marigold (Tagetes erecta L. 'Marvel') was used to investigate the role and relationship between CH4 and BRs during adventitious root (AR) formation. The results showed a dose-dependent effect of CH4 and BRs on rooting, with the greatest biological effects of methane-rich water (MRW, CH4 donor) and 2,4-epibrassinolide (EBL) at 20% and 1 µmol L- 1, respectively. The positive effect of MRW on AR formation was blocked by brassinoazole (Brz, a synthetic inhibitor of EBL), indicating that BRs might be involved in MRW-regulated AR formation. MRW promoted EBL accumulation during rooting by up-regulating the content of campestanol (CN), cathasterone (CT), and castasterone (CS) and the activity of Steroid 5α-reductase (DET2), 22α-hydroxylase (DWF4), and BR-6-oxidase (BR6ox), indicating that CH4 could induce endogenous brassinolide (BR) production during rooting. Further results showed that MRW and EBL significantly down-regulated the content of cellulose, hemicellulose and lignin during rooting and significantly up-regulated the hydrolase activity, i.e. cmcase, xylanase and laccase. In addition, MRW and EBL also significantly promoted the activity of two major cell wall relaxing factors, xyloglucan endotransglucosylase/hydrolase (XTH) and peroxidase, which in turn promoted AR formation. While, Brz inhibited the role of MRW on these substances. CONCLUSIONS: BR might be involved in CH4-promoted AR formation by increasing cell wall relaxation.
Assuntos
Brassinosteroides , Celulose , Brassinosteroides/farmacologia , Metano/farmacologia , Hidrolases , Raízes de Plantas/fisiologiaRESUMO
BACKGROUND: This study aimed to compare the cardiovascular safety of interleukin-6 inhibitors (IL-6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). METHODS: We conducted a retrospective cohort study using population-based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta-analysis was used for pooled analysis. RESULTS: We identified 8689 participants for this study. Median (interquartile range) follow-up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL-6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL-6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. CONCLUSION: There was no difference in the risk of CVE among RA patients initiated with IL-6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea.
Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Fatores de Risco de Doenças Cardíacas , Antirreumáticos/efeitos adversos , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND/PURPOSE: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS: Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P = 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium. CONCLUSION: This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes.
Assuntos
Infecções por Salmonella , Salmonella enterica , Estudos de Casos e Controles , Pré-Escolar , Surtos de Doenças , Genômica , Humanos , Infecções por Salmonella/epidemiologia , Salmonella enterica/genética , Sorogrupo , Taiwan/epidemiologiaRESUMO
MAIN CONCLUSION: HRW increased the content of starch and sucrose via regulating a series of sucrose and starch synthesis genes, which induced the formation of bulblets and adventitious roots of Lilium davidii var. unicolor. Hydrogen gas (H2), as a signaling molecule, has been reported to be involved in plant growth and development. Here, the effect of hydrogen-rich water (HRW) on the formation of bulblets and adventitious roots in the scale cuttings of Lilium davidii var. unicolor and its mechanisms at the molecular levels were investigated. The results revealed that compared with distilled water treatment (Con), the number of bulblets and adventitious roots were significantly promoted by different concentrations of HRW treatment. Treatment with 100% HRW obtained the most positive effects. RNA sequencing (RNA-seq) analysis found that compared with Con, a total of 1702 differentially expressed genes (DEGs, upregulated 552 DEGs, downregulated 1150 DEGs) were obtained under HRW treatment. The sucrose and starch metabolism, cysteine and methionine metabolism and phenylalanine metabolism were significantly enriched in the analysis of the Kyoto encyclopedia of genes and genomes (KEGG). In addition, the genes involved in carbohydrate metabolism were significantly upregulated or downregulated (upregulated 22 DEGs, downregulated 15 DEGs), indicating that starch and sucrose metabolism held a central position. The expressions of 12 DEGs were identified as coding for key enzymes in metabolism of carbohydrates was validated by qPCR during bulblet formation progress. RNA-seq analysis and expression profiles indicated that the unigene levels such as glgc, Susy, otsA and glgP, BMY and TPS were well correlated with sucrose and starch metabolism during HRW-induced bulblet formation. The change of key enzyme content in starch and sucrose metabolism pathway was explored during bulblet formation in Lilium under HRW treatment. Meanwhile, compared with Con, 100% HRW treatment increased the levels of sucrose and starch, and decreased the trehalose content, which were agreed with the expression pattern of DEGs related to the biosynthesis pathway of sucrose, starch and trehalose. Therefore, this study suggested that HRW could promote the accumulation of sucrose and starch contents in mother scales, and decreased the trehalose content, this might provide more energy for bulblet formation.
Assuntos
Lilium , Metabolismo dos Carboidratos , Hidrogênio , Lilium/genética , Amido , Sacarose , ÁguaRESUMO
Previous studies have shown that methane (CH4 ) has promoting roles in the adventitious root (AR) and lateral root (LR) formation in plants. However, whether CH4 could trigger the bulblet formation in scale cutting of Lilium davidii var. unicolor has not been elucidated. To gain insight into the effect of CH4 on the bulblet formation, different concentrations (1, 10, 50, and 100%) of methane-rich water (MRW) and distilled water were applied to treat the scale cuttings of Lilium. We observed that treatment with 100% MRW obviously induced the bulblet formation in scale cuttings. To explore the mechanism of CH4 -induced bulblet formation, the transcriptome of scales was analyzed. A total of 2078 differentially expressed genes (DEGs) were identified. The DEGs were classified into different metabolic pathways, especially phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant signal transduction. Of these, approximately 38 candidate DEGs involved in the plant signal transduction were further studied. In addition, the expression of AP2-ERF/ERF, WRKY, GRAS, ARF, and NAC transcription factors (TFs) was changed by MRW treatment, suggesting their potential involvement in bulblet formation. As for hormones, exogenous IAA, GA, and ABA could induce the bulblet formation. Additional experiments suggested that MRW could increase the endogenous IAA, GA, and JA levels, but decrease the levels of ABA during bulblet formation, which showed that higher IAA, GA, JA levels and lower ABA content might facilitate bulblet formation. In addition, the levels of endogenous hormones were consistent with the expression level of genes involved in phytohormone signal transduction. Overall, this study has revealed that CH4 might improve the bulblet formation of cutting scales in Lilium by regulating the expression of genes related to phytohormone signal transduction and TFs, as well as by changing the endogenous hormone levels.
Assuntos
Lilium , Reguladores de Crescimento de Plantas , Regulação da Expressão Gênica de Plantas , Lilium/genética , Metano , Raízes de Plantas , Transdução de Sinais , ÁguaRESUMO
Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.
Assuntos
Regulação da Expressão Gênica , Glucose/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/genética , Neovascularização Fisiológica/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Idoso , Biomarcadores , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Genes Reporter , Glucose/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Interferência de RNARESUMO
OBJECTIVES: Telomerase gene variants that lead to accelerated telomere shortening are linked to progressive-fibrosing interstitial lung diseases. However, little is known about their relationships with pneumoconiosis. This study aimed to identify TERT/TERC variants and leucocyte telomere lengths (LTL) in patients with silicosis or asbestosis. METHODS: In the present study, Sanger sequencing of TERT/TERC variants was performed in 193 Chinese Han patients with pneumoconiosis, including 109 with silicosis and 84 with asbestosis. Quantitative PCR was used to measure LTL in peripheral blood of the patients and 200 age and sex-matched healthy controls. RESULTS: In total, 7.3% patients with pneumoconiosis had 17 TERT/TERC variants. Among which 8.3% of patients with silicosis and 3.6% of patients with asbestosis had TERT variants, respectively. No TERC variants were detected in silicosis, whereas 3.6% of patients with asbestosis had TERC variants. Telomeres were significantly shorter in the patients with pneumoconiosis compared with healthy controls (p<0.001). No significant differences in LTL were found between TERT/TERC variant carriers and non-carriers. Exposure to silica dust was associated with the severity of pneumoconiosis after adjusting for covariates (OR 4.92, p=0.002). However, TERT/TERC variants and short telomeres were not associated with the severity of pneumoconiosis. CONCLUSION: Telomerase gene variants and short telomeres may be identified in the patients with silicosis and asbestosis in response to the exposure to silica or asbestos dust but are not related to disease severity.
RESUMO
Accumulation of filamentous aggregates of α-synuclein (AS) in Lewy bodies and neurites is characteristic of neurodegenerative diseases such as Parkinson's disease. Inhibition of AS fibrillation is helpful for understanding of AS aggregate structure and for developing chemical therapies. Herein, we report that the PtII -containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. PtII thus contrasts strongly with reported transition-metal ions such as MnII , FeIII , and CuII , which accelerate AS aggregation. Interaction between PtII and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtII to AS did not change the protein's overall random coil structure, as indicated by solution-state two-dimensional NMR and circular dichroism spectroscopy; and a solution of the ASâ PtII complex remained free of filamentous aggregates. Our results constitute interesting new information about the biological chemistry of metal ions in Parkinson's disease and might open new lines of research into the suppression of filamentous aggregation.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Platina/farmacologia , alfa-Sinucleína/antagonistas & inibidores , Antineoplásicos/química , Cisplatino/química , Platina/química , Agregados Proteicos/efeitos dos fármacos , Soluções , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
Normal rice wine (NRW) and waxy rice wine (WRW) were fermented to study the relationship between the structure of starch as well as the taste and texture of rice wine. The total starch content of NRW decreased to 21.2%, and that of WRW decreased to 15.6%. The water-soluble sugar content of NRW increased to 169.3, and that of WRW increased to 194.4 mg/g. The ethanol content of NRW increased to 6.5%, and that of WRW increased to 8.9%. These changes indicated that WRW exhibited higher quality than NRW. Sweetness was negatively correlated with total starch content and positively correlated with ethanol content. Starch molecules were degraded by enzymolysis, thereby enhancing crystallinity. The size of starch particle was negatively correlated with crystallinity, whereas the chewiness and gumminess of vinasse (fermented rice grains) were positively correlated with the size of starch particle and negatively correlated with crystallinity. The higher degrees of chewiness and gumminess of vinasse render the texture of WRW superior to that of NRW. The results indicated that WRW is superior to NRW in taste and texture because of the difference in starch structure.
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A continuously regenerated cationic impurity removal device (CR-CRD) has been fabricated and applied for ion chromatography (IC). The removal of cationic impurities is realized by electrodialytically replacing the cationic impurities with hydronium ions. The device is configured in a sandwich structure and the central eluent channel is respectively isolated from both electrodes by stacked cation exchange membranes and a bipolar membrane (BPM) plus stacked anion exchange membranes. The eluent channel is packed with cation exchange resins in hydronium form and their continuous regeneration can be achieved by electrodialysis. A desirable feature of the device is gas-free, and no degasser is required. It showed sufficient ability to remove cationic impurities, as indicated by > 99.9 % removal of 10 mL of 1 mM LiOH solution injected (â¼10 µmol) or continuous removal of 1 mM LiOH solution at the flow rate of 1 mL/min (1 µmol/min). A useful application was for sample pretreatment in nuclear power industry, by eliminating strong matrix interference of the sample containing LiOH (1 mM) and boric acid (2000 mg/L) with trace anion analysis.
Assuntos
Cátions , Cromatografia por Troca Iônica/métodos , Cromatografia por Troca Iônica/instrumentação , Cátions/química , Membranas Artificiais , Resinas de Troca de Cátion/química , Desenho de EquipamentoRESUMO
OBJECTIVE: This study aimed to explore the potential of employing machine learning algorithms based on intracranial pressure (ICP), ICP-derived parameters, and their complexity to predict the severity and short-term prognosis of traumatic brain injury (TBI). METHODS: A single-center prospectively collected cohort of neurosurgical intensive care unit admissions was analyzed. We extracted ICP-related data within the first 6 hours and processed them using complex algorithms. To indicate TBI severity and short-term prognosis, Glasgow Coma Scale score on the first postoperative day and Glasgow Outcome Scale-Extended score at discharge were used as binary outcome variables. A univariate logistic regression model was developed to predict TBI severity using only mean ICP values. Subsequently, 3 multivariate Random Forest (RF) models were constructed using different combinations of mean and complexity metrics of ICP-related data. To avoid overfitting, five-fold cross-validations were performed. Finally, the best-performing multivariate RF model was used to predict patients' discharge Glasgow Outcome Scale-Extended score. RESULTS: The logistic regression model exhibited limited predictive ability with an area under the curve (AUC) of 0.558. Among multivariate models, the RF model, combining the mean and complexity metrics of ICP-related data, achieved the most robust ability with an AUC of 0.815. Finally, in terms of predicting discharge Glasgow Outcome Scale-Extended score, this model had a consistent performance with an AUC of 0.822. Cross-validation analysis confirmed the performance. CONCLUSIONS: This study demonstrates the clinical utility of the RF model, which integrates the mean and complexity metrics of ICP data, in accurately predicting the TBI severity and short-term prognosis.
Assuntos
Lesões Encefálicas Traumáticas , Pressão Intracraniana , Aprendizado de Máquina , Humanos , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/diagnóstico , Pressão Intracraniana/fisiologia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Escala de Resultado de Glasgow , Escala de Coma de Glasgow , Alta do Paciente , Algoritmos , Estudos Prospectivos , Idoso , Estudos de CoortesRESUMO
BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, affecting 32 million individuals worldwide. Although atrial fibrillation has been studied for decades, a comprehensive analysis using bibliometrics has not been performed for atrial fibrillation-left atrial appendage occlusion (LAAO). Therefore, we analyzed the scientific outputs of global LAAO research and explored the current research status and hotpots from 1994 to 2022. METHODS: We searched the Web of Science core collection for publications related to LAAO that were published between 1994 and 2022. We then performed bibliometric analysis and visualization using Microsoft Excel 2021, Bibliometric (https://bibliometric.com), VOSviewer (version 1.6.19), CiteSpace (version 6.2. R2), and the Bibliometrix 4.0.0 Package (https://www.bibliometrix.org) based on the R language were used to perform the bibliometric analysis, trend and emerging foci of LAAO in the past 29 years, including author, country, institution, journal distribution, article citations, and keywords. In total, we identified 1285 eligible publications in the field of LAAO, with an increasing trend in the annual number of publications. RESULTS: The United States is the country with the most published articles in this field, while the United Kingdom is the country with the most cited literature. Mayo Clinic, from the United States, has the most publications in this area and Horst Sievert from Germany had the highest number of individual publications. The analysis of keywords showed that fibrillation, stroke, safety, oral anticoagulants, and watchman were the main hotpots and frontier directions of LAAO. Surgical treatment of nonvalvular atrial fibrillation, upgrading of related surgical instruments, and anticoagulation regimen after surgical treatment are the major research frontiers. CONCLUSION: We show that the research of percutaneous LAAO has been increasing rapidly over the last decade. Our aim was to overview past studies in the field of LAAO, to grasp the frame of LAAO research, and identify new perspectives for future research.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Humanos , Instituições de Assistência Ambulatorial , Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Bibliometria , Doença do Sistema de Condução CardíacoRESUMO
Background: The gut microbiota (GM) is widely acknowledged to have a significant impact on cardiovascular health and may act as a residual risk factor affecting cardiac structure and function. However, the causal relationship between GM and cardiac structure and function remains unclear. Objective: This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal association between GM and cardiac structure and function. Methods: Data on 119 GM genera were sourced from a genome-wide association study (GWAS) meta-analysis (13,266 European participants) conducted by the MiBioGen consortium, while data on 16 parameters of cardiac structure and function were obtained from the UK Biobank's GWAS of cardiac magnetic resonance imaging (up to 41,135 European participants). Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for causal association assessments, with sensitivity analyses conducted to reinforce the findings. Finally, biological annotation was performed on the GWAS data of GM and cardiac phenotypes with causal associations to explore potential mechanisms. Results: The MR analysis, predominantly based on the IVW model, revealed 93 causal associations between the genetically predicted abundance of 44 GM genera and 16 cardiac structure and function parameters. These associations maintained consistent directions in MR-Egger and WM models, with no evidence of pleiotropy detected. Biological annotations suggest that GM may influence cardiac structure and function through pathways involved in myocardial cell development, cardiac contractility, and apoptosis. Conclusion: The MR analysis supports a causal association between certain abundances of genetically predicted GM and cardiac structure and function, suggesting that GM could be a residual risk factor impacting cardiac phenotypes.
RESUMO
Purpose: This study aimed to analyze developmental trends in anxiety and depression after myocardial infarction (ADMI) research in the past 20 years through bibliometrics analysis and predict future research directions. Methods: ADMI-related publications were retrieved from the Web of Science Core Collection. Bibliometric, VOSviewer, CiteSpace, and Bibliometrix software packages were used for bibliometric analysis and visualization. Results: Overall, 3220 ADMI-related publications were identified. The United States, China, and the Netherlands were the countries with the most publications. Carney RM, De Jonge P, and Blumenthal JA were the most influential researchers. In 2004, Van Melle JP, from the University of Groningen, published in Psychosomatic Medicine the most cited article. "Cardiac rehabilitation" was the primary focus area. "Cardiac rehabilitation," "management," "acute coronary syndrome," and "outcome" were the top four keywords in emerging research hotspots. Notably, the effect of traditional Chinese medicine on ADMI is an area of potential research value. Conclusion: Numerous studies have underscored the significance of cardiac rehabilitation. Present research focuses on managing anxiety and depression post-acute coronary syndrome and enhancing clinical outcomes through cardiac rehabilitation technology. Additionally, the therapeutic potential of traditional Chinese medicine for ADMI is expected to attract increased attention from researchers in the future.