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Acacetin, a flavonoid compound, possesses a wide range of pharmacological effects, including antimicrobial, immune regulation, and anticancer effects. Some key steps in its biosynthetic pathway were largely unknown in flowering plants. Here, we present the first haplotype-resolved genome of Chrysanthemum indicum, whose dried flowers contain abundant flavonoids and have been utilized as traditional Chinese medicine. Various phylogenetic analyses revealed almost equal proportion of three tree topologies among three Chrysanthemum species (C. indicum, C. nankingense, and C. lavandulifolium), indicating that frequent gene flow among Chrysanthemum species or incomplete lineage sorting due to rapid speciation might contribute to conflict topologies. The expanded gene families in C. indicum were associated with oxidative functions. Through comprehensive candidate gene screening, we identified five flavonoid O-methyltransferase (FOMT) candidates, which were highly expressed in flowers and whose expressional levels were significantly correlated with the content of acacetin. Further experiments validated two FOMTs (CI02A009970 and CI03A006662) were capable of catalyzing the conversion of apigenin into acacetin, and these two genes are possibly responsible acacetin accumulation in disc florets and young leaves, respectively. Furthermore, combined analyses of ancestral chromosome reconstruction and phylogenetic trees revealed the distinct evolutionary fates of the two validated FOMT genes. Our study provides new insights into the biosynthetic pathway of flavonoid compounds in the Asteraceae family and offers a model for tracing the origin and evolutionary routes of single genes. These findings will facilitate in vitro biosynthetic production of flavonoid compounds through cellular and metabolic engineering and expedite molecular breeding of C. indicum cultivars.
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Chrysanthemum , Evolução Molecular , Flavonas , Genoma de Planta , Filogenia , Proteínas de Plantas , Chrysanthemum/genética , Chrysanthemum/metabolismo , Chrysanthemum/enzimologia , Flavonas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta/genética , Haplótipos , Diploide , Flavonoides/metabolismo , Flavonoides/biossíntese , Flores/genética , Flores/enzimologia , Flores/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismoRESUMO
BACKGROUND: Plant specialized (or secondary) metabolites (PSM), also known as phytochemicals, natural products, or plant constituents, play essential roles in interactions between plants and environment. Although many research efforts have focused on discovering novel metabolites and their biosynthetic genes, the resolution of metabolic pathways and identified biosynthetic genes was limited by rudimentary analysis approaches and enormous number of candidate genes. RESULTS: Here we integrated state-of-the-art automated machine learning (ML) frame AutoGluon-Tabular and multi-omics data from Arabidopsis to predict genes encoding enzymes involved in biosynthesis of plant specialized metabolite (PSM), focusing on the three main PSM categories: terpenoids, alkaloids, and phenolics. We found that the related features of genomics and proteomics were the top two crucial categories of features contributing to the model performance. Using only these key features, we built a new model in Arabidopsis, which performed better than models built with more features including those related with transcriptomics and epigenomics. Finally, the built models were validated in maize and tomato, and models tested for maize and trained with data from two other species exhibited either equivalent or superior performance to intraspecies predictions. CONCLUSIONS: Our external validation results in grape and poppy on the one hand implied the applicability of our model to the other species, and on the other hand showed enormous potential to improve the prediction of enzymes synthesizing PSM with the inclusion of valid data from a wider range of species.
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Arabidopsis , Genômica , Aprendizado de Máquina , Arabidopsis/genética , Arabidopsis/metabolismo , Genômica/métodos , Alcaloides/biossíntese , Alcaloides/metabolismo , Terpenos/metabolismo , Proteômica/métodos , Metabolômica/métodos , Genes de Plantas , Plantas/genética , Plantas/metabolismo , Fenóis/metabolismo , MultiômicaRESUMO
Although post-translational modification is critical to tumorigenesis, how succinylation modification of lysine sites influences hepatocellular carcinoma (HCC) remains obscure. 90 tumours and paired adjacent normal tissue of liver cancer were enrolled for succinylation staining. 423 HCC samples with 20 genes related to succinylation modification from TCGA were downloaded for model construction. Statistical methods were employed to analyse the data, including the Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbour Embedding (t-SNE) algorithm, and Cox regression analysis. The staining pan-succinyllysine antibody staining indicated that tumour tissues had a higher succinyllysine level than adjacent tissues (p < 0.001), which could be associated with a worse prognosis (p = 0.02). The survival was associated with pathological stage, tumour recurrence status and succinyllysine intensity in the univariate or multivariable cox survival analysis model. The risk model from 20 succinyllysine-related genes had the best prognosis prediction. The high expression of succinylation modification in HCC contributed to the worse patient survival prognosis. Model construction of 20 genes related to succinylation modification (MEAF6, OXCT1, SIRT2, CREBBP, KAT5, SIRT4, SIRT6, SIRT7, CPT1A, GLYATL1, SDHA, SDHB, SDHC, SDHD, SIRT1, SIRT3, SIRT5, SUCLA2, SUCLG1 and SUCLG2) could be reliable in predicting prognosis in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuína 3 , Sirtuínas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Processamento de Proteína Pós-Traducional , Lisina/metabolismo , Sirtuína 3/genética , Sirtuínas/genética , Sirtuínas/metabolismoRESUMO
AIM: To investigate the needed, unneeded and unmet health care services among rural community-dwelling older adults in China and examine the influencing factors, aiming to facilitate the global development of the home care system for a healthier world. METHODS: This cross-sectional study investigated rural areas in three provinces in Western China. A total of 1727 rural community-dwelling older adults were enrolled. The needed, unneeded and unmet health care services were assessed by the Supply and Demand of Health Care Services (SD-HCS) questionnaire for older adults. RESULTS: Respect (73%, 1265/1727) was the most needed. The other top 9 needed mainly belonged to the divisions of health monitoring and information regarding chronic diseases. Re-employment or part-time jobs (71%, 1230/1727) was the most unneeded. All five protection and safety items were the most unmet but needed. Religion was the main influencing factor of those health care services that were less unmet but needed. CONCLUSIONS: Respect was basic for older adults, and chronic disease management was in great demand among rural community-dwelling older adults. Due to low willingness and the crisis workforce, a more flexible retirement policy is needed in rural China. It is urgent to improve the emergency care system in rural areas. Last but not least, more research is needed to explore the association between religion and health.
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Serviços de Assistência Domiciliar , Vida Independente , Idoso , China , Estudos Transversais , Necessidades e Demandas de Serviços de Saúde , Humanos , População RuralRESUMO
OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Tosse/diagnóstico , Febre/diagnóstico , Faringite/diagnóstico , Pneumonia Viral/diagnóstico , Proteína Amiloide A Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , China , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Tosse/sangue , Tosse/mortalidade , Tosse/fisiopatologia , Feminino , Febre/sangue , Febre/mortalidade , Febre/fisiopatologia , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Faringite/sangue , Faringite/mortalidade , Faringite/fisiopatologia , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Prognóstico , Curva ROC , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
BACKGROUND: The changes in China's family planning policy in recent years have led to changes in the age structure of pregnant women, and the prevalence of postpartum depression (PPD) is also on the rise. Cognitive Behaviour Training (CBT) as an effective intervention is widely used for postpartum depression. However, the shortage and health disparities of mental health resources, the stigma of postpartum depression in postpartum women and the need for postpartum recovery and child care prevent postpartum women from seeking traditional face-to-face CBT. Therefore, the purpose of this proposed study is to examine the effect of mobile phone applications (App) based CBT on postpartum depression, anxiety, pressure and parenting sense of competence. METHODS: A double blind, randomized controlled trial will be used in this study to examine the effectiveness of App-based CBT in reducing the prevalence of postpartum depression compared with usual postpartum care in China. A total of 120 participants will be recruited in this study. The intervention consists of a weekly theme module app for continuous six weeks, each module including learning content and assignments. The control group received usual postpartum care content through the App. Outcome measures include postpartum depression, anxiety, pressure and parenting sense of competence at 0-, 3- and 6-month after the intervention. DISCUSSION: If our intervention is effective, it will provide a time-friendly and unrestricted intervention for the psychological care of perinatal women, which can effectively solve the shortage and unevenness of mental health resources. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900020735 . Registered 15 January 2019.
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Terapia Cognitivo-Comportamental/métodos , Depressão Pós-Parto/prevenção & controle , Aplicativos Móveis , Período Pós-Parto/psicologia , Telemedicina/métodos , Adulto , Ansiedade/prevenção & controle , Ansiedade/psicologia , China , Depressão Pós-Parto/psicologia , Método Duplo-Cego , Feminino , Humanos , Poder Familiar/psicologia , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: After China's One-child Policy was replaced with the Two-child Policy in 2013, the rate of second pregnancies with a longer inter-pregnancy interval (IPI) has suddenly increased in that country; however, the effect of long IPIs (≥49 months) on perinatal outcomes remains unreported. METHODS: This was a retrospective cohort study in China from July 2015 through June 2016. We used univariate and multivariate logistic regression models to test the associations among IPI, maternal age, and perinatal outcome (preterm delivery, term low birthweight, and small-for-gestational age). We included baseline factors and variables with biological plausibility as confounders. RESULTS: Our analytic sample included 3309 second pregnancies. The mean IPI was 75.36 months. Compared with second pregnancies with a short IPI of 7-24 months, those with long IPIs had higher adjusted odds ratios (ORs) of preterm delivery (1.70-2.00 [95% CI 1.20-3.33]) and term low birthweight (2.16-2.68 [1.10-6.17]), but not small-for-gestational age. The mean maternal age at current delivery was 32.0 years. Compared with the reference group (25-29 years), second pregnancies for the oldest maternal age group (≥35 years) showed no statistically significant increased ORs for adverse perinatal outcomes. CONCLUSION: Long IPI is a significant contributor to preterm delivery and term low birthweight. Health care providers need to pay close attention to preterm delivery prevention and fetal growth during prenatal care for second pregnancies where the mothers have long IPIs.
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Nascimento Prematuro/epidemiologia , Adulto , Intervalo entre Nascimentos , China , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Idade Materna , Análise Multivariada , Razão de Chances , Gravidez , Cuidado Pré-Natal , Política Pública , Estudos RetrospectivosRESUMO
Aptamer-based strip assay is an easy, highly efficient and low-cost detection method, which has been developed and easily applied to onsite detection. A new sensitive sandwich dipstick assay for adenosine triphosphate (ATP) detection was successfully developed based on specific recognition between split aptamer fragments and the target. In this method, the thiolated aptamer was first conjugated to the surface of gold nanoparticles (AuNPs), while the biotin-aptamer was immobilized on the surface of a nitrocellulose filter in the test line. In the presence of ATP, the thiol-aptamer/ATP/biotin-aptamer complexes were generated, which led to an obvious increase in optical signals at the test line. Under the optimal determination conditions, an excellent linear logarithmic response to the ATP concentration was obtained within the range of 0.5 µM to 5 mM. The limit of detection (LOD) of 0.5 µM was reached at a signal-to-noise ratio of 3. The dipstick assay showed a good average recovery of 96-108 % with the RSD of less than 20 % in urine samples. The proposed method exhibited high specificity against other nucleotides such as the uridine triphosphate (UTP), cytidine triphosphate (CTP), and guanosine triphosphate (GTP). The results indicated that the dipstick strip may be considered as an inexpensive screening tool for onsite ATP determination. Graphical Abstract A simple split aptamer fragments based sandwich-type dipstick assay was developed for ATP detection.
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Trifosfato de Adenosina/análise , Técnica de Seleção de Aptâmeros/métodos , Aptâmeros de Nucleotídeos/química , Biotina/química , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Técnica de Seleção de Aptâmeros/instrumentação , Sensibilidade e EspecificidadeRESUMO
Cyromazine (CYR) can cause serious damage to the organs of animals or human beings, and it was found to bind to polythymine (polyT10) via multiple hydrogen bonding interactions. Based on this novel finding, a highly sensitive and simple colorimetric method was developed for CYR detection by using label-free gold nanoparticles (AuNPs) and polyT10. Under the optimized conditions, excellent linearity was acquired for CYR within the range of 1-500 ng mL(-1). In addition, the spectra and color changes of the AuNP solution were measured by spectrophotometry and observed by the naked eye, and the results showed that as low as 1 and 5 ng mL(-1) of CYR could be detected, depending upon the measurement methods. Afterwards, cucumber was selected to investigate the sample matrix effect and a sample pretreatment procedure was developed with simple homogenization and filtration. Even after 200 times dilution, the limit of detection (LOD) and limit of quantitation (LOQ) reached 252 ng g(-1) and 500 ng g(-1), respectively. The LOD and LOQ satisfied the Chinese requirement for the maximum residue limit (MRL), which is 0.5-1 µg g(-1) of CYR in most vegetables. The assay also showed a good average recovery of 83.7-104.8% with the RSD of less than 7% and good selectivity for cyromazine over other pesticides that may exist in vegetable samples. The method proposed in this study was simple, fast, and highly sensitive and accurate, and the test result with this method was visible to the naked eye. Therefore, it could be used for routine determination of CYR residues in cucumber samples.
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Cucumis sativus/química , Ouro/química , Nanopartículas Metálicas/química , Praguicidas/análise , Triazinas/análise , Colorimetria/métodos , Limite de Detecção , Poli T/química , Espectrofotometria Ultravioleta/métodosRESUMO
Histone deacetylation affects Candida albicans (C. albicans) pathogenicity by modulating virulence factor expression and DNA damage. The histone deacetylase Sir2 is associated with C. albicans plasticity and maintains genome stability to help C. albicans adapt to various environmental niches. However, whether Sir2-mediated chromatin modification affects C. albicans virulence is unclear. The purpose of our study was to investigate the effect of Sir2 on C. albicans pathogenicity and regulation. Here, we report that Sir2 is required for C. albicans pathogenicity, as its deletion affects the survival rate, fungal burden in different organs and the extent of tissue damage in a mouse model of disseminated candidiasis. We evaluated the impact of Sir2 on C. albicans virulence factors and revealed that the Sir2 null mutant had an impaired ability to adhere to host cells and was more easily recognized by the innate immune system. Comprehensive analysis revealed that the disruption of C. albicans adhesion was due to a decrease in cell surface hydrophobicity rather than the differential expression of adhesion genes on the cell wall. In addition, Sir2 affects the distribution and exposure of mannan and ß-glucan on the cell wall, indicating that Sir2 plays a role in preventing the immune system from recognizing C. albicans. Interestingly, our results also indicated that Sir2 helps C. albicans maintain metabolic activity under hypoxic conditions, suggesting that Sir2 contributes to C. albicans colonization at hypoxic sites. In conclusion, our findings provide detailed insights into antifungal targets and a useful foundation for the development of antifungal drugs. IMPORTANCE: Candida albicans (C. albicans) is the most common opportunistic fungal pathogen and can cause various superficial infections and even life-threatening systemic infections. To successfully propagate infection, this organism relies on the ability to express virulence-associated factors and escape host immunity. In this study, we demonstrated that the histone deacetylase Sir2 helps C. albicans adhere to host cells and escape host immunity by mediating cell wall remodeling; as a result, C. albicans successfully colonized and invaded the host in vivo. In addition, we found that Sir2 contributes to carbon utilization under hypoxic conditions, suggesting that Sir2 is important for C. albicans survival and the establishment of infection in hypoxic environments. In summary, we investigated the role of Sir2 in regulating C. albicans pathogenicity in detail; these findings provide a potential target for the development of antifungal drugs.
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Candida albicans , Candidíase , Parede Celular , Evasão da Resposta Imune , Sirtuína 2 , Candida albicans/genética , Candida albicans/patogenicidade , Candida albicans/imunologia , Parede Celular/metabolismo , Animais , Candidíase/microbiologia , Candidíase/imunologia , Camundongos , Sirtuína 2/metabolismo , Sirtuína 2/genética , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Virulência , Modelos Animais de Doenças , Deleção de Genes , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Camundongos Endogâmicos BALB C , FemininoRESUMO
INTRODUCTION: There is a growing emphasis on the importance of the availability of specialist palliative care for people with motor neuron disease (MND). However, the palliative care needs of this population and the utilisation of different specialist services remain poorly defined. OBJECTIVES: To (1) describe clinical characteristics, symptom burden and functional levels of patients dying with MND on their admission to palliative care services; (2) determine factors associated with receiving inpatient or community palliative care services. DESIGN: An observational study based on point-of-care assessment data from the Australian Palliative Care Outcomes Collaboration. PARTICIPANTS: A total of 1308 patients who received palliative care principally because of MND between 1 January 2013 and 31 December 2020. MEASURES: Five validated clinical instruments were used to assess each individual's function, distress from symptoms, symptom severity and urgency and acuity of their condition. RESULTS: Most patients with MND had no or mild symptom distress, but experienced a high degree of functional impairment. Patients who required 'two assistants for full care' relative to those who were 'independent' (OR=11.53, 95% CI: 4.87 to 27.26) and those in 'unstable' relative to 'stable' palliative care phases (OR=16.74, 95% CI: 7.73 to 36.24) were more likely to use inpatient versus community-based palliative care. Associations between the use of different palliative care services and levels of symptom distress were not observed in this study. CONCLUSIONS: Patients with MND were more likely to need assistance for decreased function and activities of daily living, rather than symptom management. This population could have potentially been cared for in the palliative phase in a community setting if greater access to supportive services were available in this context.
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Doença dos Neurônios Motores , Cuidados Paliativos , Humanos , Doença dos Neurônios Motores/terapia , Cuidados Paliativos/estatística & dados numéricos , Masculino , Feminino , Idoso , Austrália , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , AdultoRESUMO
Stem color is an important agronomic trait of wax gourds. However, its regulatory genes have not been identified. In this study, 105 inbred lines constructed from two parents (GX-71 and MY-1) were sequenced and quantitative trait loci sequencing was used to mine the genes that regulate stem color in wax gourds. The results identified two quantitative trait loci related to stem color, qSC5 and qSC12, located on Chr05 (11,134,567-16,459,268) and Chr12 (74,618,168-75,712,335), respectively. The qSC5 had a phenotypic variation rate of 36.9% and a maximum limit of detection of 16.9. And the qSC12 had a phenotypic variation rate of 20.9%, and a maximum limit of detection of 11.2. Bch05G003950 (named BchAPRR2) and Bch12G020400 were identified as candidate genes involved in stem color regulation in wax gourds. The chlorophyll content and expression of BchAPRR2 and Bch12G020400 were significantly higher in green-stemmed wax gourds than in white-stemmed ones. Therefore, BchAPRR2 and Bch12G020400 were considered the main and secondary regulatory genes for wax gourd stem color, respectively. Finally, InDel markers closely linked to BchAPRR2 were developed to validate the prediction of wax gourd stem color traits in 55 germplasm lines, with an accuracy of 81.8%. These findings lay the foundation for exploring the genetic regulation of wax gourd stem color and future research on wax gourd breeding.
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Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027-2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253-2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042-1.126, P < 0.001), sepsis (HR = 2.387, 95 % CI: 1.707-3.338, P < 0.001), high neutrophil-to-lymphocyte ratio (NLR) (HR = 1.010, 95 % CI: 1.003-1.017, P = 0.007), and high D-dimer level (HR = 1.005, 95 % CI: 1.001-1.009, P = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination (HR = 0.625, 95 % CI: 0.440-0.886, P = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 (95 % CI: 0.641-0.923) and 0.814 (95 % CI: 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 (95 % CI: 0.765-0.962) and 0.875 (95 % CI: 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value. Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions.
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Several studies have revealed that an imbalance of the intestinal microbiota is involved in intestinal inflammation associated with ulcerative colitis (UC). Therefore, regulating the homeostasis of gut microbiota is critical for treating UC. Dracocephalum moldavica L. (DML) extract, a common traditional Chinese medicine, has been demonstrated to possess numerous pharmacological effects, such as antioxidative, antiinflammatory, and antibacterial properties. The aim of the present study was to evaluate the beneficial effects of DML extract and the probable mechanism of action in a dextran sulfate sodiuminduced chronic colitis model. It was found that DML extract ameliorated UC by improving disease activity index, weight loss, colon length, and histological scoring. DML extract administration also enhanced the count of Lactobacillus and reduced the count of Romboutsia. Furthermore, the results of network pharmacology analysis revealed that the active ingredients (including luteolin, rosmarinic acid, oleanolic acid, ursolic acid, apigenin, acacetin, kaempferol, and isorhamnetin) in the DML extract were closely associated with antiinflammatory activity via various signaling pathways, including the NFκB, IL17, TNF, and Tolllike receptor (TLR) signaling pathways. Western blot analysis further indicated that DML extract downregulated the expression of members of the TLR4/NFκB signaling pathway, which was associated with colitis. Thus, it was hypothesized that DML extract exerted its anticolitis effects by modulating the gut microbiota and inflammatory pathways.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Ratos , Camundongos , NF-kappa B , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Long-term drought induced by low rainfall leads to environmental degradation of land in arid and semi-arid regions. In past decades, re-vegetation of degraded sandy soils to prevent soil erosion has been widely employed, including in Mu Us Sandy Land, which suffers from severe soil erosion. However, it remains unclear how re-vegetation affects soil properties and soil microbes after long restoration periods. In this study, typical plots planting Artemisia ordosica and Salix psammophila were selected to investigate the influence of plant types on soil properties; an area of bare sandy land was used as a control. The results show that re-vegetation increased soil organic carbon (C), total nitrogen (N), soil microbial carbon, microbial nitrogen and soil organic acid, while decreasing soil total phosphorous (TP) content significantly, resulting in increased C/P and N/P ratios. Correlation analysis showed that TP was negatively correlated with oxalic acid (OA) and acetic acid (AA), indicating that increased AA and OA content could accelerate the active utilization of phosphorus and induced low TP in soil. Re-vegetation with A. ordosica significantly decreased the microbial diversity of topsoil. The redundancy analysis showed that TP was main index in affecting microbes. These results that lower P content, higher C/P and N/P ratio and influence of TP on microbes suggest that phosphorus is the main limiting factor for re-vegetation and growth of soil microorganisms. In the future, strategies for the development of sustainable ecosystems in regions suffers from severe soil erosion should consider phosphorus supplementation.
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Ecossistema , Solo , Areia , Fósforo/análise , Carbono/análise , Plantas , China , Nitrogênio/análiseRESUMO
PURPOSE: A nomograph model of predicting the risk of post-operative central nervous system infection (PCNSI) after craniocerebral surgery was established and validated. METHODS: The clinical medical records of patients after cranial surgery in Renmin Hospital of Wuhan University from January 2020 to September 2022 were collected, of whom 998 patients admitted to Shouyi Hospital District were used as the training set and 866 patients admitted to Guanggu Hospital District were used as the validation set. Lasso regression was applied to screen the independent variables in the training set, and the model was externally validated in the validation set. RESULTS: A total of 1864 patients after craniocerebral surgery were included in this study, of whom 219 (11.75%) had PCNSI. Multivariate logistic regression analysis showed that age > 70 years, a previous history of diabetes, emergency operation, an operation time ≥ 4 h, insertion of a lumbar cistern drainage tube ≥ 72 h, insertion of an intracranial drainage tube ≥ 72 h, intraoperative blood loss ≥ 400 mL, complicated with shock, postoperative albumin ≤ 30 g/L, and an ICU length of stay ≥ 3 days were independent risk factors for PCNSI. The area under the curve (AUC) of the training set was 0.816 (95% confidence interval (95%CI), 0.773-0.859, and the AUC of the validation set was 0.760 (95%CI, 0.715-0.805). The calibration curves of the training set and the validation set showed p-values of 0.439 and 0.561, respectively, with the Hosmer-Lemeshow test. The analysis of the clinical decision curve showed that the nomograph model had high clinical application value. CONCLUSION: The nomograph model constructed in this study to predict the risk of PCNSI after craniocerebral surgery has a good predictive ability.
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OBJECTIVES: (1) To compare palliative care needs of patients admitted primarily with stroke and (2) to determine how the care needs of these patients affect their use of different types of specialist palliative care services. METHODS: Observational study based on point-of-care data from the Australian Palliative Care Outcomes Collaboration. Multivariate logistic regression models were used to explore the association between patients' palliative care needs and use of community versus inpatient specialist palliative care services. RESULTS: The majority of patients who had a stroke in this study population had mild or no symptom distress, but experienced a high degree of functional impairment and needed substantial help with basic tasks of daily living. A lower Australia-modiï¬ed Karnofsky Performance Status score (OR=1.82, 95% CI 1.06 to 3.13) and occurrence of an 'unstable' palliative care phase (OR=28.34, 95% CI 9.03 to 88.94) were associated with use of inpatient versus community palliative care, but otherwise, no clear association was observed between the majority of symptoms and use of different care services. CONCLUSIONS: Many people with stroke could potentially have been cared for and could have experienced the terminal phases of their condition in a community setting if more community support services were available for their families.
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Spark plasma sintering is a new technology for preparing ceramic materials. In this article, a thermal-electric-mechanical coupled model is used to simulate the spark plasma sintering process of boron carbide. The solution of the thermal-electric part was based on the charge conservation equation and the energy conservation equation. A phenomenological constitutive model (Drucker-Prager Cap model) was used to simulate the densification process of boron carbide powder. To reflect the influence of temperature on sintering performance, the model parameters were set as functions of temperature. Spark plasma sintering experiments were conducted at four temperatures: 1500 °C, 1600 °C, 1700 °C, and 1800 °C, and the sintering curves were obtained. The parameter optimization software was integrated with the finite element analysis software, and the model parameters at different temperatures were obtained through the parameter inverse identification method by minimizing the difference between the experimental displacement curve and the simulated displacement curve. The Drucker-Prager Cap model was then incorporated into the coupled finite element framework to analyze the changes of various physical fields of the system over time during the sintering process.
RESUMO
Background and Aims: The aim was to establish a liver venous deprivation (LVD) model in rats, compare hepatic hypertrophy between LVD and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS), and explore the underlying mechanisms. Methods: The LVD or extended-LVD (e-LVD) group received portal vein ligation (PVL) combined with hepatic vein ligation (HVL). The ALPPS or e-ALPPS group received PVL plus parenchyma ligation. Liver regeneration was assessed by measuring the liver weight and performing pathological analysis. Liver functions and the sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor 1 (S1PR1) pathway were also investigated. Results: All future liver remnants (FLRs) in the ALPPS, e-ALPPS, LVD, and e-LVD groups exhibited significant hypertrophy compared with the control group. The LVD and e-LVD procedures induced similar liver hypertrophy than that in the corresponding ALPPS groups. Furthermore, the LVD and e-LVD methods led to obvious cytolysis in the venous-deprived lobes as well as a noticeable increase in serum transaminase levels, while no necrosis was observed in the ALPPS and e-ALPPS groups. SPHK1/S1P/S1PR1 pathway were distinctly activated after operation, especially in congestive/ischemic livers. Conclusions: We describe the first rat model of LVD and e-LVD with simultaneously associated HVL and PVL. Compared with the ALPPS technique, the LVD or e-LVD procedure had a comparable overall effect on the hypertrophy response and a stronger effect on liver function. The SPHK1/S1P/S1PR1 pathway was involved in the LVD- or ALPPS-induced liver remodeling.
RESUMO
AIMS: Taurohyodeoxycholic acid (THDCA), a natural 6α-hydroxylated bile acid, exhibits intestinal anti-inflammatory effects. This study aimed to explore the efficacy of THDCA on ulcerative colitis and to reveal its mechanisms of action. MAIN METHODS: Colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to mice. Mice in the treatment group were gavage THDCA (20, 40, and 80 mg/kg/day) or sulfasalazine (500 mg/kg/day) or azathioprine (10 mg/kg/day). The pathologic markers of colitis were comprehensively assessed. The levels of Th1-/Th2-/Th17-/Treg-related inflammatory cytokines and transcription factors were detected by ELISA, RT-PCR, and Western blotting. The balance of Th1/Th2 and Th17/Treg cells was analyzed by Flow cytometry. KEY FINDINGS: THDCA significantly alleviated colitis by improving the body weight, colon length, spleen weight, histological characteristics, and MPO activity of colitis mice. THDCA reduced the secretion of Th1-/Th17-related cytokines (IFN-γ, IL-12p70, IL-6, IL-17A, IL-21, IL-22, and TNF-α) and the expressions of transcription factors (T-bet, STAT4, RORγt, and STAT3), but increase the production of Th2-/Treg-related cytokines (IL-4, IL-10, and TGF-ß1) and the expressions of transcription factors (GATA3, STAT6, Foxp3, and Smad3) in the colon. Meanwhile, THDCA inhibited the expressions of IFN-γ, IL-17A, T-bet, and RORγt, but improved the expression of IL-4, IL-10, GATA3, and Foxp3 in the spleen. Furthermore, THDCA restored the proportion of Th1, Th2, Th17, and Treg cells, and balanced the Th1/Th2 and Th17/Treg immune response of colitis mice. SIGNIFICANCE: THDCA can alleviate TNBS-induced colitis via regulating Th1/Th2 and Th17/Treg balance, which may represent a promising treatment for patients with colitis.