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BACKGROUND: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. METHOD: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-scale variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. RESULTS: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R2-scores > 0.01 for 71.55 % of metabolites. CONCLUSION: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.
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Metabolómica , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma , Humanos , Metabolómica/métodos , Desequilibrio de LigamientoRESUMEN
Objective:To evaluate the correlation between vascular hyperintensity of magnetic resonance fluid-attenuated inversion recovery (FLAIR) sequence(FVH) and related parameters of magnetic resonance perfusion weighted imaging (MR-PWI) in patients with middle cerebral artery stenosis cerebral infarction, and to explore the hemodynamic factors related to FVH and the effect of FVH on the short-term clinical prognosis of patients.Methods:A total of 116 patients with middle cerebral artery stenosis cerebral infarction in the Department of Neurology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from January 2020 to December 2022 were collected.According to the diagnostic criteria of FVH, they were divided into FVH (+ ) group (78 cases) and FVH(-) group (38 cases). All patients underwent magnetic resonance(MR) and MR-PWI scans.Demographic and cerebrovascular risk factors were collected, clinical neurological function of patients was assessed by national institate of health stroke scale(NIHSS) upon admission and discharge, and cognitive function of patients was assessed by mini-mental state examination (MMSE). Short-term clinical outcome was assessed using modified Rankin scale(mRS) at the 90th day after discharge.The degree of middle cerebral artery stenosis, positive or negative FVH, FVH score, hypoperfusion volume and MR-PWI related parameters, including peak time (Tmax), mean transit time (MTT), cerebral blood volume (CBV) and cerebral blood flow (CBF), were evaluated in relation to clinical symptoms.SPSS 22.0 statistical software was used for t test, Chi-square test and Pearson correlation analysis. Results:There were significant differences in hypoperfusion volume, Tmax, MTT and CBF between FVH (+ ) group and FVH(-) group( t=1.989, 3.830, 5.223, 3.911, all P<0.05). In terms of short-term clinical outcome, the improvement rate of neurological function ((8.25±6.39)%, (12.22±6.08)%) and MMSE score(25.48±1.59), (26.31±1.26) in FVH (+ ) group were significantly lower than those in FVH(-) group, and the number of patients with progressive stroke during hospitalization in FVH(+ ) group was more than that of FVH(-) group(22(28.21%), 4(10.53%)) (all P<0.05). Pearson correlation analysis showed that FVH score was positively correlated with hypoperfusion volume ( r=0.786, P<0.01) and MTT ( r=0.692, P<0.01), and negatively correlated with CBF ( r=-0.568, P<0.01), but no significant correlation with the degree of arterial stenosis ( r=0.363, P>0.05). Conclusion:FVH is closely related to the Tmax, MTT and CBF values shown in MR-PWI, and the incidence of stroke in progression and short-term adverse prognosis are more likely in FVH(+ ) group, suggesting that FVH can be used as a convenient imaging indicator to reflect the hypoperfusion status of patients with middle cerebral artery stenosis cerebral infarction, and can provide an objective basis for further individualized treatment.
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To explore the effect of monoculture and mixture sowing artificial grassland on the photosynthetic characteristics of Leymus chinensis and Medicago sativa, we determined the diurnal variation of photosynthetic properties of L. chinensis and M. sativa under different treatments. The results showed that the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type' in monoculture, the stomatal conductance of M. sativa showed 'unimodal type', and the stomatal conductance and water use efficiency of L. chinensis showed 'bimodal type'. Under the mixed sowing treatment, the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type', the stomatal conductance and water use efficiency of L. chinensis showed 'unimodal type', and the stomatal conductance of M. sativa showed 'bimodal type'. The peak photosynthetic rate of L. chinensis under mixture was signi-ficantly higher than that under monoculture, being 17.72 and 13.65 µmol CO2·m-2·s-1, respectively. Under monoculture and mixture sowing treatments, the chlorophyll content of L. chinensis was higher than that of M. sativa, nitrogen content of the leaves of L. chinensis was lower than that of M. sativa, and the nitrogen content in the leaves of mixture sowing L. chinensis was significantly higher than that of monoculture sowing L. chinensis, which were 27.60 and 22.55 g·kg-1, respectively. Net photosynthetic rates of L. chinensis and M. sativa were significantly positively correlated with stomatal conductance and transpiration rate, and significantly negatively correlated with intercellular CO2 concentration under different planting methods. Net photosynthetic rate of M. sativa was significantly positively correlated with blade temperature and water use efficiency. In summary, mixed sowing was beneficial to enhance nitrogen content of L. chinensis. Our results provided a theoretical basis for the response of the photosynthetic characteristics of forage to planting mode of artificial grassland.
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Dióxido de Carbono , Medicago sativa , Pradera , Fotosíntesis/fisiología , Poaceae , Hojas de la Planta/fisiología , Agua , NitrógenoRESUMEN
Aging induces a series of alterations, specifically a decline in the stature and number of villi and crypts in the small intestine, thus compromising the absorbent capability of the villi. This investigation employed a senolytic combination of dasatinib and quercetin (D+Q) to examine its impact on the intestinal tract of elderly mice. Our findings demonstrate that D+Q treatment leads to a decrease in the expression of p21, p16, and Ki67, while concurrently triggering removal of apoptotic cells within the villi. Additionally, D+Q treatment exhibits the ability to promote growth in both the height and quantity of villi and crypts, along with stimulating nitric oxide (NO) production in aged mice. The study presented a model to assess strategies to alleviate age-related senescence in the intestinal tract of elderly mice. Importantly, D+Q showcases promising potential in enhancing intestinal functionality within the aging.
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INTRODUCTION: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. OBJECTIVES: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. METHODS: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. RESULTS: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVß5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. CONCLUSION: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.
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Trampas Extracelulares , Pancreatitis , Ratones , Animales , Trampas Extracelulares/metabolismo , Pancreatitis/metabolismo , Fibronectinas/farmacología , Fibronectinas/metabolismo , Enfermedad Aguda , Neutrófilos/metabolismo , Inflamación/metabolismo , Acetato de Tetradecanoilforbol/metabolismo , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The current lithospheric root of the South China Block has been partly removed, yet what mechanisms modified the lithospheric structure remain highly controversial. Here we use a new joint seismic inversion algorithm to image tabular high-velocity anomalies at depths of ~90-150 km in the asthenosphere beneath the convergent belt between the Yangtze and Cathaysia blocks that remain weakly connected with the stable Yangtze lithosphere. Based on obtained seismic images and available geochemical data, we interpret these detached fast anomalies as partially destabilized lower lithosphere that initially delaminated at 180-170 Ma and has relaminated to their original position after warming up in the mantle by now. We conclude that delamination is the most plausible mechanism for the lithospheric modification and the formation of a Mesozoic Basin and Range-style magmatic province in South China by triggering adiabatic upwelling of the asthenosphere and consequent lithospheric extension and extensive melting of the overlying crust.
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Memory performance evaluation has generally been based on behavioral tests in the past decades. However, its neural correlates remain largely unknown, particularly in humans. Here we addressed this question using intracranial electroencephalography in patients with refractory epilepsy, performing an episodic memory test. We used the presurgical Wechsler Memory Scale (WMS) test to assess the memory performance of each patient. We found that hippocampal ripples significantly exhibited a transient increase during visual stimulation or before verbal recall. This increase in hippocampal ripples positively correlated with memory performance. By contrast, memory performance is negatively correlated with hippocampal interictal epileptic discharges (IEDs) or epileptic ripples in the memory task. However, these correlations were not present during quiet wakefulness. Thus, our findings uncover the neural correlates of memory performance in addition to traditional behavioral tests.
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Electroencefalografía , Epilepsia , Humanos , Hipocampo , Cognición/fisiología , Recuerdo MentalRESUMEN
Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.
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Sequías , Glycine max , Glycine max/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloruro de Sodio/farmacología , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico , Zinc/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Chinese hamster ovary (CHO) cells are commonly used as "bio-machines" to pro-duce monoclonal antibodies (mAb) because of their ability to produce very complex proteins. In this study, we evaluated the effects of pine needle water extract (PNWE), pine needle ethanol extract (PNEE), and pine needle polysaccharide extract (PNPE) on the CHO cell growth, mAb production and quality using a Fed-batch culture process. PNPE maintained high VCD and viability, and the titer increase was correlated with its concentration. Three extracts effectively reduced the acidic charge variant and modulated mAb glycosylation. PNPE had the most profound effect, with G0F decreasing by 8.7% and G1Fa increasing by 6.7%. The change in the glycoform was also closely related to the PNPE concentration. This study demonstrated that PNPE could facilitate CHO cell growth, increase the mAb production, decrease acidic charge variants, and regulate mAb glycoforms. To identify the components responsible for the above changes, the sugar and flavonoid contents in the extracts were determined, and the chemical compounds were identified by LC-MS, resulting in 38 compounds identified from PNPE. Rich in sugars and flavonoids in these three extracts may be related to increased CHO cell growth and productivity, and changes in glycoforms.
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Anticuerpos Monoclonales , Técnicas de Cultivo Celular por Lotes , Cricetinae , Animales , Cricetulus , Células CHO , Técnicas de Cultivo Celular por Lotes/métodosRESUMEN
INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.
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Diabetes Mellitus , Pancreatitis , Humanos , Índice de Severidad de la Enfermedad , Pancreatitis/diagnóstico , Estudios Retrospectivos , Hemoglobina Glucada , Enfermedad Aguda , Pronóstico , Gravedad del Paciente , Diabetes Mellitus/epidemiologíaRESUMEN
AIM To prepare cucurbitacin B nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method.With stabilizer type,stabilizer-drug ratio and homogeneous frequency as influencing factors,particle size and PDI as evaluation indices,the formulation was optimized by single factor test,after which the solubility and stability were determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of cucurbitacin B,physical mixture and cucurbitacin B nanosuspensions(10 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,8,10,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of cucurbitacin B,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was hydroxypropyl cellulose+sodium dodecyl sulfate(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-drug ratio,80 MPa for homogeneous pressure,and 12 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 200 nm,0.140 and-32 mV,respectively.The nanosuspensions demonstrated obviously higher solubility than that of raw medicine and physical mixture,along with good stability within 6 months.Cucurbitacin B existed in the nanosuspensions in an amorphous state.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened tmax(P<0.01),prolonged t1/2(P<0.05,P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 4.32 times as compared with that of raw medicine.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of cucurbitacin B.
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Objective:To study the effect of visceral fat area (VFA) on postoperative complications and pancreatic fistula in patients undergoing laparoscopic assisted radical gastrectomy for gastric careinoma.Methods:Clnical data of 214 primary gastric cancer patients undergoing laparoscopic assisted radical gastrectomy between Jan 2017 and Jan 2022 at the Department of General Surgery, Shouguang People's Hospital were retrospectively reviewed.Results:There were 85 patients in high VFA group and 129 patients in the low VFA group. The body mass index (25.1±3.4) kg/m 2 and visceral fat area (143.4±41.1) cm 2 in the high VFA group were higher than those in the low VFA group (21.2±2.9) kg/m 2 and visceral fat area (58.7±31.9) cm 2. The operative time was (228.3±53.1) min vs. (206.3±62.9) min ( t=5.538, P=0.017). The intraoperative blood loss was (264.6±173.6) ml vs. (213.9±156.2) ml ( t=3.373, P=0.035). The postoperative hospital stay was (12.5±4.0) d vs. (10.3±3.7) d ( t=7.781, P=0.013). Twenty-three cases developed postoperative complications in the high VFA group vs. 20 cases in the low VFA group ( χ2=4.261, P=0.039). Patients in the high VFA group had an incidence of clinically relevant pancreatic fistula of 10.6% vs. 3.1% in patients in the low VFA group ( χ2=5.034, P=0.038). Univariate and multivariate analysis of clinically relevant pancreatic fistulas in patients with different VFA groups showed that men ≥134.6 cm 2 and women ≥91.1 cm 2 with VFA and operative time ≥250 min were independent risk factors for the occurence of clinically relevant pancreatic fistulas after laparoscopic assisted radical gastrectomy. Conclusions:VFA increases the difficulty of laparoscopic-assisted radical gastrectomy, resulting in increased postoperative complications. VFA and operation time are independent risk factors for clinically relevant pancreatic fistula after radical gastrectomy for gastric cancer.
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This paper analyzed the research status of living wills at home and abroad from three aspects: the status of living wills knowledge-attitude-practice, the influencing factors of the living wills development, and the effects of living wills. It also provided some suggestions for promoting the development of living wills in China. In foreign countries, a large number of quantitative and qualitative studies have been carried out in this regard, and the research contents were relatively in-depth. However, China initiated late in this field, and the research contents and methods were relatively simple. Living wills not only protect patients’ decision-making right, but also promote the rational distribution of medical resources, as well as ensure the fairness of health services. For China, with a large population and uneven distribution of health resources, living wills have broad implementation prospects.
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Background: In China, physicians aged 30-45 years who work in tertiary hospitals perform most of the clinical duties, especially outpatient services, and the high-intensity, high-pressure workplace may through long-term sedentary affect their health, particularly urinary health. Methods: The study, conducted from October 2020 to October 2021, included male physicians in Xiangya Hospital, the Second Xiangya Hospital, and the Third Xiangya Hospital of Central South University (Hunan, China). They were divided into surgeon and non-surgeon groups. We collect the data on age, body mass index (BMI), duration of outpatient duties and the International Prostate Symptom Score-voiding (IPSS-V) and IPSS-storage (IPSS-S), and the IPSS-Total, and the IPSS-Quality of Life Index (IPSS-QOL), and the Athens insomnia scale (AIS), and the International Prostate Symptom Score (IIEF-5). Results: The duration of outpatient duties positively correlated with IPSS-Total (P<0.001), IPSS-S (P<0.001), and IPSS-QOL (P<0.001) and negatively correlated with IIEF-5 (p=0.032). Compared to non-surgeons, surgeons performed fewer outpatient duties. The IPSS-Total (P=0.016), IPSS-Storage (P=0.005), and QOL scores (P=0.046) of the non-surgeon group were higher and the IIEF-5 scores were lower (P=0.039). There were no significant differences between the groups regarding age, body mass index, IPSS-Voiding, and Athens insomnia scale scores. A positive correlation between outpatient visit duration and lower urinary tract symptoms (LUTS) in the IPSS-Storage subscale was observed and there was a weak negative correlation between duration of outpatient duties and the IIEF-5 score. Conclusions: Compared to surgeons, non-surgeons had more outpatient duties, and they experienced more severe LUTS and sexual dysfunction, which suggests that outpatient duties maybe should not be more than 4 days/week in Chinese tertiary medical centers.
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Objective: This systematic review and meta-analysis aimed to compare the diagnostic performance of transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE) for staging liver fibrosis in patients with chronic viral hepatitis (CVH). Methods: Pubmed, Embase, Web of Science, and Cochrane Library were searched (-01/08/2021) for studies comparing TE with 2D-SWE in patients with CVH. Other etiologies of chronic liver disease (CLD) and articles not published in SCI journals were excluded. The bivariate random-effects model was used to pool the performance of the TE and 2D-SWE. Results: Eight articles with a total of 1301 CVH patients were included. The prevalence of significant fibrosis (fibrosis stage ≥ 2), advanced fibrosis (fibrosis stage ≥ 3), and cirrhosis was 50.8%, 44.8%, and 34.7%, respectively. 2D-SWE expressed higher overall accuracy than TE in detecting significant fibrosis (0.93 vs. 0.85, P = 0.04). No significant difference among the overall diagnostic accuracy of TE and 2D-SWE in staging advanced fibrosis and cirrhosis was found. Conclusion: TE and 2D-SWE express good to excellent diagnostic accuracies to stage fibrosis in CVH patients. 2D-SWE compares favorably with TE especially for predicting significant fibrosis.
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Diagnóstico por Imagen de Elasticidad , Hepatitis Viral Humana , Hepatopatías , Diagnóstico por Imagen de Elasticidad/métodos , Hepatitis Crónica/patología , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/patología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico , Hepatopatías/patologíaRESUMEN
BACKGROUND: Serum ferritin (SF), as an acute-phase response protein, is used to reflect the degree of oxidative stress and systemic inflammatory responses. This study was designed to assess the effect of elevated SF levels on the severity of acute pancreatitis (AP). METHODS: From January 2013 to December 2020, 200 consecutive patients with AP were retrospectively reviewed to analyze the relationships among the etiologies of pancreatitis, the severity of the disease and SF levels. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess whether elevated SF levels could predict the onset of organ failure in AP. RESULTS: 92 (46%) had high SF levels (> 275 ng/ml). SF levels were not associated with the etiology of AP disease. Among patients with high SF levels, there was a significant increase in the proportion of patients with severe AP (23.1% vs. 76.9%) and a higher proportion of systemic inflammatory response scores (25.9% vs. 44.6%) in comparison to patients with normal SF levels. The area under the ROC curve for SF in predicting persistent organ failure was 0.812 [95% confidence interval 0.721-0.904]. CONCLUSIONS: F concentrations were positively correlated with the severity of AP, and quantitative assessment of SF can predict disease severity and organ failure in patients with AP.
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Hiperferritinemia , Pancreatitis , Enfermedad Aguda , Reacción de Fase Aguda , Estudios de Cohortes , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
Epitope mapping of the interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Abs is challenging because of complexity in protein three-dimensional structures. Protein structure fingerprint technology was applied for epitope mapping of 44 SARS-CoV-2 Abs with three-dimensional structure complexes. The results defined how the epitopes were distributed on SARS-CoV-2 and how the patterns of six CDRs from Abs participated in neutralization. Also, the residue-residue recognition revealed that certain residues had higher frequencies on the interfaces between SARS-CoV-2 and Abs, and the activity correlated with the physicochemical properties of the residues at the interface. Thus, epitope mapping provides significant lead information for development of epitope-based designs for Abs, vaccines, and diagnostic reagents. This is a bioinformatics project of structural data analysis; no animals or cells were used.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Mapeo Epitopo , Epítopos , Humanos , Glicoproteínas de Membrana , Glicoproteína de la Espiga del Coronavirus , Proteínas del Envoltorio ViralRESUMEN
A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50 = 0.647 µg/mL against phytopathogen Xanthomonas oryzae pv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 µg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.
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Infecciones Bacterianas , Nanopartículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Preparaciones de Acción Retardada , Compuestos Heterocíclicos con 2 Anillos , Humanos , Imidazolidinas , Compuestos MacrocíclicosRESUMEN
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), is an acute infectious disease transmitted by ticks that has recently been identified. There are no reports of epidemic serotypes in Liaoning Province, PR China. The aim of this study was, therefore, to identify genotypes of SFTSV in this province. METHODS: In 2019, quantitative PCR testing was performed on 17 patients suspected of being infected with SFTS in Liaoning Province and on 492 ticks from the counties and cities surrounding the patients' residences. Four samples were subjected to virus isolation and whole-genome amplification. RESULTS: Molecular diagnostic results confirmed SFTSV infection in five of the 17 suspected cases of SFTS and in 12 of the 492 ticks, with a prevalence of 2.4%. Four strains of SFTSV were successfully isolated from patients' blood and ticks. Phylogenetic analysis after whole-genome amplification and sequencing showed that they all belonged to genotype A of SFTSV. CONCLUSIONS: This study is the first to determine the genotype of SFTSV in patients and ticks in Liaoning Province, PR China. The results deepen our understanding of the SFTS epidemic and provide information on the variability in mortality rate among genotypes.