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1.
J Immunother Cancer ; 9(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34642245

RESUMO

BACKGROUND: Aging has long been thought to be a major risk factor for various types of cancers. However, accumulating evidence indicates increased resistance of old animals to tumor growth. An in-depth understanding of how old individuals defend against tumor invasion requires further investigations. METHODS: We revealed age-associated alterations in tumor-infiltrating immune cells between young and old mice using single-cell RNA and coupled T cell receptor (TCR) sequencing analysis. Multiple bioinformatics methods were adopted to analyze the characteristics of the transcriptome between two groups. To explore the impacts of young and old CD8+ T cells on tumor growth, mice were treated with anti-CD8 antibody every 3 days starting 7 days after tumor inoculation. Flow cytometry was used to validate the differences indicated by sequencing analysis between young and old mice. RESULTS: We found a higher proportion of cytotoxic CD8+ T cells, naturally occurring Tregs, conventional dendritic cell (DC), and M1-like macrophages in tumors of old mice compared with a higher percentage of exhausted CD8+ T cells, induced Tregs, plasmacytoid DC, and M2-like macrophages in young mice. Importantly, TCR diversity analysis showed that top 10 TCR clones consisted primarily of exhausted CD8+ T cells in young mice whereas top clones were predominantly cytotoxic CD8+ T cells in old mice. Old mice had more CD8+ T cells with a 'progenitor' and less 'terminally' exhausted phenotypes than young mice. Consistently, trajectory inference demonstrated that CD8+ T cells preferentially differentiated into cytotoxic cells in old mice in contrast to exhausted cells in young mice. Importantly, elimination of CD8+ T cells in old mice during tumor growth significantly accelerated tumor development. Moreover, senescent features were demonstrated in exhausted but not cytotoxic CD8+ T cells regardless of young and old mice. CONCLUSIONS: Our data revealed that a significantly higher proportion of effector immune cells in old mice defends against tumor progression, providing insights into understanding the altered kinetics of cancer development and the differential response to immunotherapeutic modulation in elderly patients.

2.
Org Lett ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633205

RESUMO

A method for the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines through Sonogashira cross-coupling/nucleophilic addition tandem reactions using calcium carbide as a solid alkyne source, 2-(2-bromophenyl)benzimidazoles as starting materials, and copper as a catalyst is described. The target products can also be synthesized through one-pot three-component reactions of o-phenylenediamines, o-bromobenzaldehydes, and calcium carbide. Both reaction routes can also be scaled up to gram scale.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1456-1461, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627424

RESUMO

OBJECTIVE: To investigate the effect of ß-arrestin1 on the concentration of reactive oxygen species (ROS) in the mitochondria of acute T-lymphocytic leukemia (T-ALL) cells and its possible mechanisms. METHODS: The stable T-ALL cell line with knocked down ß-arrestin1 (Jurkat Siß1) was constructed. Flow cytometry and probe assays were used to detect ROS content in cell and mitochondrial, respectively. The relationship between ß-arrestin1 and microRNA was detected, analyzed and Q-PCR confirmed by microRNA microarray. The target genes of microRNA were predicated by miRbase software, identified by Western blot, and validated by Dual luciferase reporter gene. RESULTS: Jurkat Siß1 stable cell line was successfully constructed and it was found that ROS content was slightly reduced in Jurkat Siß1 at the whole cell level, and the ROS content was also significantly reduced in mitochondria. MicroRNA microarray analysis revealed that multiple T-ALL related microRNAs showed differentially expressed, in which the expression of miR-652-5p was significantly increased in Jurkat Siß1 (P<0.05 fold>2.0), and Q-PCR showed that miR-652-5p was nearly 5-fold up-regulated in Jurkat Siß1. miRbase predicted that the P62 gene was the target gene of miR-652-5p which could regulates mitochondrial function. P62 protein showed highly expressed in stably knocked down miR-652-5p in Jurkat cells. Dual luciferase reporter gene assay confirms that P62 was the target gene of miR-652-5p. CONCLUSION: ß-arrestin1 can decreases the expression of miR-652-5p and deregulates the translational inhibition of P62 mRNA, thus to increase ROS content in mitochondria of T-ALL cells.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , MicroRNAs/genética , Mitocôndrias , Oxigênio , RNA Mensageiro , beta-Arrestina 1
4.
Sci Rep ; 11(1): 17421, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465820

RESUMO

Corona Virus Disease 2019 (COVID-19) has spread rapidly to countries all around the world from the end of 2019, which caused a great impact on global health and has had a huge impact on many countries. Since there is still no effective treatment, it is essential to making effective predictions for relevant departments to make responses and arrangements in advance. Under the limited data, the prediction error of LSTM model will increase over time, and its prone to big bias for medium- and long-term prediction. To overcome this problem, our study proposed a LSTM-Markov model, which uses Markov model to reduce the prediction error of LSTM model. Based on confirmed case data in the US, Britain, Brazil and Russia, we calculated the training errors of LSTM and constructed the probability transfer matrix of the Markov model by the errors. And finally, the prediction results were obtained by combining the output data of LSTM model with the prediction errors of Markov Model. The results show that: compared with the prediction results of the classical LSTM model, the average prediction error of LSTM-Markov is reduced by more than 75%, and the RMSE is reduced by more than 60%, the mean [Formula: see text] of LSTM-Markov is over 0.96. All those indicators demonstrate that the prediction accuracy of proposed LSTM-Markov model is higher than that of the LSTM model to reach more accurate prediction of COVID-19.


Assuntos
COVID-19/epidemiologia , Brasil/epidemiologia , Aprendizado Profundo , Humanos , Cadeias de Markov , Redes Neurais de Computação , Projetos de Pesquisa , Federação Russa/epidemiologia , Reino Unido/epidemiologia , Estados Unidos
5.
Anat Rec (Hoboken) ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536264

RESUMO

This study aimed to uncover the potential mechanism of Erchen decoction (ECD) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Network pharmacology and bioinformatics were used to determine the active components of ECD and its potential target in treating NAFLD. High fat diet (HFD)-induced NAFLD mice model was used. Liver tissues were stained with hematoxylin and eosin, and Oil Red O. Serum lipid profiles and hepatic inflammatory molecules in lipopolysaccharide (LPS)/Toll-like receptor-4 (TLR-4) pathway were confirmed by enzyme-linked immunosorbent assay. Intestinal barrier function, including intestinal epithelial tight junction (IETJ) proteins, fecal short-chain fatty acids (SCFAs) concentration and intestinal microbiota composition, was also assessed. Screening relevant databases revealed 123 active components and 158 potential target proteins in ECD, as well as 1,783 differential genes for NAFLD. Enrichment analyses predicted that the regulation of LPS, cholesterol metabolism and inflammatory pathways might be the underlying mechanisms of ECD in NAFLD treatment. ECD ameliorated the multi-profiles of NAFLD and reversed the high levels of inflammatory molecules such as, serum LPS, hepatic TLR-4, tumor necrosis factor-α, and interleukin-1ß. Additionally, ECD upregulated the concentration levels of IETJ proteins and fecal SCFAs. 16s RNA sequencing indicated that ECD can improve the gut microbiota, such as Akkermansia, Clostridium XIVa, Coprococcus, and Ruminococcus. The current study demonstrated that ECD can reverse the HFD-induced intestinal barrier dysfunction, thereby reducing the LPS translocation and alleviating the hepatic inflammation, and eventually exhibiting a protective effect against NAFLD.

6.
Protein Expr Purif ; 188: 105968, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34481960

RESUMO

Human ß-defensins are an important family of innate host defense peptides with pleiotropic activities. Human ß-defensin 36 (DEFB136) is a novel member of the ß-defensin family which have not been characterized so far. In the present research, the DEFB136 peptide was expressed successfully and purified using the IMPACT-TWIN 1 expression system. The purified DEFB136 peptide was identified by MALDI-TOF mass spectrometry and circular dichroism spectroscopy. While the recombinant DEFB136 peptide exhibited a broad spectrum of antimicrobial activity against E. coli, Staphylococcus aureus and Candida albicans strains, but had low cytotoxicity to human erythrocytes. In addition, the result of the octet assay showed that the DEFB136 had a high lipopolysaccharide (LPS)-binding affinity, suggesting the DEFB136 may be involved in immunoregulation through its LPS neutralization. These results may help lay the groundwork to understand better the complex interaction between innate host defense and the diversity of the defensin family.

7.
Ecotoxicol Environ Saf ; 224: 112675, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34438273

RESUMO

Veterinary antibiotics are widely used in animal agriculture. Owing to its good absorption in the gastrointestinal tract, strong tissue permeability, and long biological half-life, doxycycline (DOX) is widely used to treat bacterial infections; however, this use can pose an environmental risk. The adsorption/desorption and degradation of DOX in three agricultural soils were investigated. DOX rapidly adsorbed to the soils, with an adsorption equilibrium time of 12 h for the three soils. The Freundlich equation was used to fit the adsorption and desorption of DOX in soils. A high Freundlich affinity coefficient (KF) was obtained from Freundlich isotherms, indicating strong sorption of DOX to agricultural soils and weak mobility to aquatic environment. Soil organic matter, the clay ratio and the cation exchange capacity were significantly positively correlated with KF (P < 0.05). The half-life (DT50) of DOX degradation in the soils ranged from 2.51 to 25.52 d. Soil microorganisms, soil moisture, temperature, the initial concentration, illumination and soil texture all significantly affected the degradation of DOX in soil (P < 0.05). When 8% (w/w) manure was added, DOX degradation was significantly accelerated (P < 0.05). Biotic and abiotic factors affected the degradation of DOX in soils. These results indicated that soil properties and environmental conditions greatly affected the fate and transport of DOX into agricultural soils.

8.
Bosn J Basic Med Sci ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34392828

RESUMO

Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.

9.
Neuroradiology ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34374821

RESUMO

PURPOSE: To explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM). METHODS: Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson's partial correlation. RESULTS: Compared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = - 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = - 0.484). CONCLUSION: VM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients.

10.
Clin Ther ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34366153

RESUMO

PURPOSE: Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. METHODS: In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. FINDINGS: After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC0-∞ and Cmax were 1200 (274) h · ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h · ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of Cmax, AUC0-t, and AUC0-∞ were 64% (54%-76%), 80% (76%-85%), and 80% (76%-85%), respectively. The median (range) Tmax was prolonged from 1.5 (1-3) hours in the fasted condition to 2 (1.5-6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. IMPLICATIONS: In the present study, the consumption of a high-fat meal prior to henagliflozin administration was associated with reductions in AUC0-∞ and Cmax of 19.4% and 36.4%, respectively. However, based on the analysis of the pharmacokinetic/pharmacodynamic findings on henagliflozin, this slight change may not have clinical significance. Mass balance of henagliflozin in humans was achieved with ∼75% of the administered dose recovered in excretions within 4 days after administration whether in the fasted or fed state. These findings suggest that henagliflozin tablets can be administered with or without food.

11.
J Pharm Sci ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34416271

RESUMO

A liquid chromatography-mass spectrometry (LC-MS) method was developed to provide a fingerprint of polysorbate 80 (PS80) subspecies that enables identification of PS80 degradation pathway. The developed method demonstrates unique monoester peak profile of PS80 from different vendors, attributed by differences in relative abundance of the fatty acid monoesters. The LC-MS method was also applied to examine the susceptibility of PS80, at different grades, to auto-oxidation and hydrolysis. PS80 oxidative degradation induced by iron or occurred in open bottle without nitrogen overlay was found to follow the same pathway, but at a much faster rate in the former scenario. The oxidation preferentially occurs at the double bond of fatty acid chains, thus providing explanation on the faster degradation observed in PS80 at Chinese Pharmacopia (ChP) grade than at multi-compendial (MC) grade. In contrast, the difference in susceptibility of MC and ChP grade PS80 against esterase-induced hydrolysis in placebo was not pronounced. The method was also able to provide a fingerprint to identify both PS80 hydrolysis and oxidation in mAb drug product stability samples, but it requires a solid phase extraction step to remove protein prior to the analysis.

13.
J Bioenerg Biomembr ; 53(4): 405-413, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34363569

RESUMO

Heat shock protein 70 (HSP70) can regulate astrocyte viability under hypoxic and ischemic conditions. However, the protective mechanism involved is not completely clear. This study aimed to investigate whether HSP70 protects U87 glioma cells against hypoxic damage via the extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways. Lentivirus-mediated HSP70-siRNA was used for HSP70 silencing. U87 glioma cells with lentiviral infection were exposed to hypoxia for 4, 8, 12, and 24 h, respectively, followed by a 24-h reoxygenation treatment. A Cell-Counting Kit-8 was then used to evaluate the viability of the U87 glioma cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels, respectively. The expression of HSP70, p-ERK1/2, p-AKT, and U87 cell viability were increased after 8 h of hypoxia/24 h of reoxygenation (P < 0.01). However, HSP70 silencing significantly decreased the U87 cell viability after the hypoxia/reoxygenation treatment (P < 0.01). The protein expressions of p-ERK1/2 and p-AKT also decreased in HSP70-silenced U87 cells (P < 0.01). In conclusion, HSP70 inhibition suppressed the viability of U87 glioma cells during hypoxia/reoxygenation (at least partially) by inhibiting the ERK1/2 and PI3K/AKT signaling pathways. This study may help to understand the molecular mechanisms underlying the progression and development of cerebral hypoxia-ischemia.

14.
Geriatr Nurs ; 42(5): 1105-1108, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34274688

RESUMO

The purpose of this study was to assess the effectiveness of Pfizer-BioNTech COVID19 vaccine among nursing home residents by exploring the outcomes of a major COVID-19 outbreak following COVID-19 vaccination in a nursing home located at a metropolitan area of South-Central Texas. 91 residents resided in this nursing home during the outbreak, and 86 residents received the 1st dose of COVID-19 vaccine on January 4th, 2021. A retrospective chart review explored outcomes of this outbreak by accessing the electronic medical records from January 4th, 2021 thru February 28th, 2021. Residents partially vaccinated with COVID-19 vaccine were found less likely to be symptomatic during this outbreak. The risk of SARS-CoV-2 infection was significantly lower among residents who received both doses of the COVID-19 vaccine. Completion of both doses of COVID vaccination for all nursing home residents is essential and can prevent future COVID-19 outbreaks in nursing homes.

15.
mSystems ; : e0015821, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282934

RESUMO

The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level (P < 5 × 10-8) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota, Firmicutes, Lactobacillus, and Gardnerella vaginalis and the beta diversity weighted UniFrac (P < 1 × 10-5). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(6): 721-726, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296693

RESUMO

OBJECTIVE: To analyze risk factors for the occurrence and progression of isolated distal deep vein thrombosis (IDDVT) of lower limbs, and to explore the predictive value of dynamic changes of coagulation index D-dimer on the occurrence and progression of IDDVT in acute brain injury (ABI) patients during perioperative period. METHODS: A retrospective case-control study was conducted. Perioperative ABI patients admitted to department of neurocritical care unit (NCCU) of the First Affiliated Hospital of University of Science and Technology of China from September 2019 to May 2020 were enrolled. Patients' baseline characteristics, disease characteristics, treatment approaches, outcomes and coagulation function index at 1, 2-4, 5-7 and > 7 days post operation were analyzed between patients with IDDVT and patients with progressive IDDVT. Risk factors for IDDVT occurrence and progression were identified by multivariate Logistic regression. Receiver operating characteristic curve (ROC curve) were drawn to assess the predictive value of coagulation indexes for IDDVT occurrence and progression. RESULTS: A total of 164 ABI patients were enrolled. Most of the patients were elderly [age was 60 (51, 69) years], male [99 cases (60.4%)], and severe cases [Glasgow coma score (GCS) at admission was 6 (5, 8)]. The rates of IDDVT occurrence and progression were 61.6% (101 cases) and 16.8% (17 cases), respectively, the rate of proximal deep venous thrombosis (DVT) was 12.8% (21 cases). Compared with the IDDVT group (101 patients), patients without IDDVT group were younger (years: 55±13 vs. 62±13), length of intensive care unit (ICU) stay were shorter (days: 12±6 vs. 15±7), body mass index (BMI) and GCS at admission were higher [59 patients, BMI (kg/m2): 23±5 vs. 19±8, GCS scores: 7±2 vs. 6±2], the differences were statistically significant (all P < 0.05). Compared with patients with IDDVT progression group, male patients were fewer [61.9% (52/84) vs. 88.2% (15/17)], the proportion of transfusion of red blood cell and anticoagulant therapy were lower [8.3% (7/84) vs. 29.4% (5/17) and 47.6% (40/84) vs. 94.1% (16/17)], the proportion of cerebral herniation was higher [42.9% (38/84) vs. 11.8% (2/17)] in patients without IDDVT progressive group. All of the differences were statistically significant (all P < 0.05). D-dimer were increased in two groups of whether IDDVT occurrence or not over time. D-dimer peaked on 5-7 days after surgery in IDDVT occurrence group, and then decreased. D-dimer peaked at > 7 days after surgery in patients without IDDVT. With time, D-dimer were increased in groups of whether IDDVT progression or not, both peaked at 5-7 days postoperation, and then decreased. Compared with non-IDDVTgroup, D-dimer was significantly increased in IDDVT group from 2-4 days after surgery [mg/L: 4.1 (2.3, 8.0) vs. 2.4 (1.7, 3.4), P < 0.05], and lasted until 5-7 days [mg/L: 5.5 (3.3, 11.4) vs. 3.9 (2.6, 5.8), P < 0.05]. Compared with IDDVT group, D-dimer was significantly increased in IDDVT progressive group from 2-4 days [mg/L: 11.2 (4.7, 20.0) vs. 3.7 (2.1, 6.8), P < 0.05], and lasted until 7 days [mg/L: 11.0 (3.0, 18.9) vs. 4.1 (2.6, 6.5), P < 0.05]. Multivariate Logistic regression analysis showed that age > 60 years [odds ratio (OR) = 3.43, 95% confidence interval (95%CI) was 1.69-6.96, P = 0.001], GCS score at admission > 8 (OR = 0.35, 95%CI was 0.17-0.76, P = 0.008), length of ICU stay > 13 days (OR = 2.25, 95%CI was 1.08-4.70, P = 0.031) were risk factors for IDDVT. Gender (OR = 0.19, 95%CI was 0.02-0.71, P = 0.019), transfusion of red blood cell (OR = 6.50, 95%CI was 1.33-31.94, P = 0.021), cerebral herniation (OR = 0.18, 95%CI was 0.37-0.90, P = 0.036) were risk factors for IDDVT profression. ROC curve analysis showed that age and D-dimer at 5-7 days were predicators of IDDVT [the area under curve ROC (AUC) were 0.68 and 0.72, 95%CI were 0.60-0.75 and 0.64-0.80, both P value were 0.000 1]. When the cut-off value of age was 60 years old and the D-dimer was 5.4 mg/L, the sensitivity were 60.6% and 54.4%, specificity were 71.2% and 80.9%, respectively, positive predictive value were 78.7%, 84.5%, negative predictive value were 51.2%, 48.1%, respectively. The elevation of D-dimer to 3.9 times at days 5-7 compared with day 1 of NCCU stay was a predicator of IDDVT progression (AUC = 0.81, 95%CI was 0.71-0.88, P = 0.000 1). The sensitivity, specificity, positive predictive value and negative predictive value were 76.5%, 74.6%, 41.9% and 93.0%, respectively. CONCLUSIONS: IDDVT occurrence and progressiveare common in severe ABI patients during perioperative period. The dynamic change of D-dimer, especially at days 5-7, is a valuable predictor of IDDVT progressionin ABI patients, which is helpful for guiding implementation of deep vein ultrasound of lower limb.


Assuntos
Lesões Encefálicas , Trombose Venosa , Idoso , Estudos de Casos e Controles , China , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos
18.
J Environ Manage ; 297: 113366, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314962

RESUMO

The widespread usage of veterinary antibiotics results in antibiotic contamination and increases environmental risks. This study was evaluated the single and ternary competitive adsorption-desorption and degradation of three amphenicol antibiotics (AMs): chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FF) in three agricultural soils. The adsorption capacity of amphenicol antibiotics in the soil was weak, and the Kf value was in the range of 0.15-3.59 µg1-1/nL1/n kg-1. In the single adsorption-desorption experiment, the ranked order of adsorption capacity was TAP > FF > CAP. However, in the ternary competitive adsorption experiment, the order was changed to be CAP > FF > TAP. The degradation of AMs in soils was performed at various conditions. All AMs were vulnerable to microbial degradation in soils. A higher initial concentration would reduce the degradation rate and enhance the persistence of AMs in soil. The degradation of AMs was positively influenced by changes in soil moisture content and culture temperatures up to 30 °C and decreased at higher temperatures. An equation was used to predict the leachability of AMs in soils and assess their risk to the water environment. The weak adsorption capacity and poor persistence of FF indicated that it may have a strong effect on groundwater based on the equation. It is imperative to further assess the biological impacts of FF at environmentally relevant concentrations given its mobility and extensive use in the livestock industry.


Assuntos
Poluentes do Solo , Solo , Adsorção , Antibacterianos , Cloranfenicol/análise , Poluentes do Solo/análise
19.
J Hematol Oncol ; 14(1): 90, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108020

RESUMO

The chimera antigen receptor (CAR) T cell therapy is a novel and potential targeted therapy and has achieved satisfactory efficacy in patients with relapsed or refractory multiple myeloma (MM) in recent years. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics. To explore the potential biomarkers in plasma for evaluating CRS and clinical efficacy, we performed metabolomic and lipidomic profiling of plasma samples from 17 relapsed or refractory MM patients received CAR-T therapy. Our study showed that glycerophosphocholine (GPC), an intermediate of platelet-activating factor (PAF)-like molecule, was significantly decreased when the participants underwent CRS, and the remarkable elevation of lysophosphatidylcholines (lysoPCs), which were catalyzed by lysoPC acyltransferase (LPCAT) was a distinct metabolism signature of relapsed or refractory MM patients with prognostic value post-CAR-T therapy. Both GPC and lysoPC are involved in platelet-activating factor (PAF) remodeling pathway. Besides, these findings were validated by LPCAT1 expression, a key factor in the PAF pathway, associated with poor outcome in three MM GEP datasets of MM. In conclusion, CAR-T therapy alters PAF synthesis in MM patients, and targeting PAF remodeling may be a promising strategy to enhance MM CAR-T therapy.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/terapia , Fator de Ativação de Plaquetas/metabolismo , Humanos , Metabolismo dos Lipídeos , Metaboloma , Biossíntese de Proteínas
20.
Plant Biotechnol J ; 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174007

RESUMO

Single-cell RNA-seq (scRNA-seq) has been highlighted as a powerful tool for the description of human cell transcriptome, but the technology has not been broadly applied in plant cells. Herein, we describe the successful development of a robust protoplast cell isolation system in the peanut leaf. A total of 6,815 single cells were divided into eight cell clusters based on reported marker genes by applying scRNA-seq. Further, a pseudo-time analysis was used to describe the developmental trajectory and interaction network of transcription factors (TFs) of distinct cell types during leaf growth. The trajectory enabled re-investigation of the primordium-driven development processes of the mesophyll and epidermis. These results suggest that palisade cells likely differentiate into spongy cells, while the epidermal cells originated earlier than the primordium. Subsequently, the developed method integrated multiple technologies to efficiently validate the scRNA-seq result in a homogenous cell population. The expression levels of several TFs were strongly correlated with epidermal ontogeny in accordance with obtained scRNA-seq values. Additionally, peanut AHL23 (AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN 23), which is localized in nucleus, promoted leaf growth when ectopically expressed in Arabidopsis by modulating the phytohormone pathway. Together, our study displays that application of scRNA-seq can provide new hypotheses regarding cell differentiation in the leaf blade of Arachis hypogaea. We believe that this approach will enable significant advances in the functional study of leaf blade cells in the allotetraploid peanut and other plant species.

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