Although some studies have identified a possible link between the De Ritis ratio and the mortality of patients with COVID-19), the predictive value and the optimal cut-value remain unclear. This study aimed to explore the correlation between the De Ritis ratio and mortality in hospitalized COVID-19 . The data for this cohort study came from a retrospective cohort study that was carried out in a medical system in New York City. The primary outcome was the in-hospital mortality of included patients. The researchers ran multivariate Cox regression analyses, curve fitting, and subgroup analysis to support our findings. Overall survival in different De Ritis ratio groups was plotted as Kaplan–Meier survival curves. The study enrolled 4371 participants with COVID-19 from March 1, 2020 to April 16, 2020. The overall mortality was 24.8% (1082/4371). The curve fitting analyses indicated that the De Ritis ratio has a positive linear connection with mortality in patients with COVID-19. After adjusting for all covariates, participants with a De Ritis ratio ≥2 exhibited 1.29 times the risk of in-hospital mortality compared with those with a De Ritis ratio <1 (hazard ratio 1.29, 95% confidence interval 1.02–1.62, p = 0.031). The p for trend was <0.05 for all models. Patients in the group with a De Ritis ratio ≥2 experienced the shortest survival time in the Kaplan–Meier survival analysis. A higher baseline De Ritis ratio is correlated with a corresponding higher mortality among hospitalized people with COVID-19.
Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the 3D pair-wise motion of distal chromosomal elements, such as enhancers and promoters, is essential and necessitates dynamic fluidity. Therefore, the interplay of chromosome organization and dynamics is crucial for gene regulation. Here, we use a live imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output in the developing fly embryo while systematically varying the genomic separation between these two DNA loci. Our analysis reveals a combination of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation and lead to long-ranged correlations compared to existing polymer models. This scaling implies that encounter times of DNA loci are much less dependent on genomic separation than predicted by existing polymer models, with potentially significant consequences for eukaryotic gene expression.
Objective To study the immune function of dendritic cells(DC)from peripheral blood of patients with positive preS1 protein chronic hepatitis B(CHB).Methods Monocytes were purified from peripheral blood of health volunteers(control group1,10 cases),patients with negative preS1 protein chronic hepatitis B(control group2,10 cases)and patients with positive preS1 protein chronic hepatitis B(experimental group,10 cases)with incubation of granulocyte/macrophage colony stimulating factor(GM-CSF),interleukin-4(IL-4)and interferon-γ(IFN-γ)which was added on day 6.The abilities to stimulate the proliferation of allogenic T cells were evaluated by MTT assay,and the levels of TNF-α and IL-12 p40+p70 in culture supernatant of DCs were detected by ELISA.Results The abilities to stimulate the proliferation of allogenic T cells by DCs and the levels of TNF-α and IL-12 p40+p70 in culture supernatant of DCs in experimental group were significantly less than those in control group 1(P0.01),but there was no difference versus control group2(P0.05).Conclusion It is suggested that the patients with CHB have the defective immune function of DCs.In the period of HBV persistence infection,there is no direct relativity between the function of DC from peripheral blood of CHB and positive preS1 protein.
Objective To observe the stimulatory effect of IFN-γ on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (MoDCs).Methods Monocytes were purified from peripheral blood of health volunteers with incubation of granulocyte/macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and interferon-γ (IFN-γ,1×106 U/L and 2×106U/L) which was added on day 5.The expressions of CD83 and MHC-DR on DCs were analyzed by FACS,the abilities to stimulate the proliferation of allogenic T cells were evaluated by MTT assay,and the levels of IL-12 p40+p70 in culture supernatant of DCs were detected by ELISA.Results IFN-γ at the two concentrations could up-regulate the expression of CD83 and MHC-DR,stimulate DCs to secrete a high level of IL-12 p40+p70, and IFN-γ activated DCs could enhance the proliferation of allogenic T cells.Furthermore,IFN-γ 1×106 U/L was more effective.Conclusion IFN-γ can effectively enhance the functional differentiation and maturation of MoDC.
Nanoparticles have been widely applied as gene carrier for improving RNA interference (RNAi) efficiency in medical and agricultural fields. However, the mechanism and delivery process of nanoparticle-mediated RNAi is not directly visualized and elucidated. Here we synthesized a star polymer (SPc) consisted of a hydrophilic shell with positively-charged tertiary amine in the side chain, which was taken as an example to investigate the mechanism in gene delivery. The SPc could assemble with dsRNA spontaneously through electrostatic force, hydrogen bond and van der Waals force. Interestingly, the SPc could protect dsRNA from degradation by RNase A and insect hemolymph, thus remarkably increasing the stability of dsRNA. Meanwhile, the SPc could efficiently promote the cellular uptake and endosomal escape for intracellular spreading of dsRNA. Transcriptome analysis revealed that the SPc could up-regulate some key genes such as Chc, AP2S1 and Arf1 for activating clathrin-mediated endocytosis. Furthermore, the suppression of endocytosis hindered the cellular uptake of SPc-delivered dsRNA in vitro, and the subsequent RNAi effect was also disappeared in vivo. To our knowledge, our study is the first direct visualization of the detailed cellular delivery process and mechanism of nanocarrier-mediated gene delivery. Above mechanism supports the application of nanocarrier-based RNAi in gene therapy and pest management.
This study aimed to improve the functional properties of egg white protein (EWP) by covalent modification of EWP with xanthan gum (XG) and gallic acid (GA)/tannic acid (TA) to form covalent complexes. The results showed that grafting degrees of EWP-GA-XG and EWP-TA-XG complexes reached 37.23% and 44.01%, respectively. After the covalent reaction of EWP with GA/TA and XG, the secondary structure changed, the α-helix content decreased, the β-sheet content increased, and the structure of EWP became looser. The radical scavenging rates of DPPH and ABTS of EWP-GA-XG (44.94%, 56.38%) and EWP-TA-XG (85.45%, 88.39%) complexes were found to be significantly enhanced compared with EWP (7.90%, 12.94%). The emulsion activity index and emulsion stability index of EWP-GA-XG (10.05 m2/g, 96.43%) and EWP-TA-XG (11.04 m2/g, 96.53%) complexes were also improved as compared to EWP (5.94 m2/g, 51.45%). Moreover, the peak transition temperatures of EWP-GA-XG (138.05 °C) and EWP-TA-XG (143.96 °C) complexes were higher than that of EWP (125.00 °C). This study may provide the theoretical basis for improving the functional properties of EWP and expanding its application in the field of food.
Objective To study the clinical significance of detecting the serum Cystatin C(CysC),Microalbuminuria(MA),β2-microglobin (β2-MG) and blood Urea (Urea),Creatinine (Cr) in cancer patients treated with chemotherapy.Methods Serum level of CysC,MA,β2-MG and Urea,Cr were detected in 50 patients with malignant tumor at baseline and 1,3,7,15 days after treated with chemotherapy respectively.Their levels pre-and post-chemotherapy were analysed.Results serum level of β2-MG increased significantly at 1 d postchemotherapy;Urea MA and serum CysC incerased simultaneously in the following days.The levels of CysC,MA,β2-MG were significant higher than that at baseline.Conclusion Detecting the levels of CysC,MA,β2-MG had a higher valuation in early diagnosing renal function damage and are more sensitive than blood Urea and Cr in the early diagnosis of renal function damage.
Key words:
Serum Cystatin C; Mieroalbuminuria; β2-microglobin; Malignant tumor; Renal function damage
Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-β1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-β1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene. Smad7-enhanced green fluorescent protein (EGFP)-BMSCs stably expressing Smad7 were subsequently co-cultured with hepatic stellate cells (HSCs) for 48 h. Smad7 and TGF-β1 levels in the culture medium were detected using ELISA, and the levels of collagen (Col) I, Col III, laminin (LN) and hyaluronic acid (HA) were measured using immunoassays. The early apoptosis rates of HSCs were determined via flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to evaluate the mRNA and protein expression profiles, respectively. The results indicated that Smad7-EGFP-BMSCs stably expressing Smad7 were successfully constructed. Upon co-culturing with rat Smad7-EGFP-BMSCs, the early apoptotic rate of HSCs was significantly increased (P<0.05). Levels of Smad7 in the culture medium were also significantly increased (P<0.05), whereas the levels of TGF-β1, Col I, Col III, LN and HA were significantly decreased (P<0.05). Furthermore, the mRNA and protein levels of Smad7 and matrix metalloproteinase 1 were significantly increased (P<0.05), whereas those of TGF-β1, α-SMA, Smad2, smad3, TGF-β receptor I, Col I, tissue inhibitors of metalloproteinase-1 and Col III were significantly decreased. The results of the present study suggest that rat BMSCs overexpressing Smad7 may inhibit the fibrosis of HSCs by regulating the TGF-β1/Smad signaling pathway. This provides a novel insight into future treatments for liver fibrosis.
ABSTRACT Microscopic bioluminescence imaging has been historically challenging due to a lack of detection methods and easily resolved probes. Here we combine bioluminescence with phasor analysis, an optical method commonly used to distinguish spectrally similar fluorophores. Bioluminescent phasor enabled rapid differentiation of multiple luciferase reporters and resonance energy transfer processes. The merger of bioluminescence and phasor analysis provides a platform for routine, time-lapse imaging of collections of cellular features.
A long-standing question in metazoan gene regulation is how remote enhancers communicate with their target promoters over long distances. Combining genome editing and quantitative live imaging we simultaneously visualize physical enhancer–promoter communication and transcription in Drosophila embryos. Enhancers regulating pair rule stripes of even-skipped expression activate transcription of a reporter gene over a distance of 150 kb. We show in individual cells that activation only occurs after the enhancer comes into close proximity with its regulatory target and that upon dissociation transcription ceases almost immediately. We further observe distinct topological conformations of the eve locus, depending on the spatial identity of the activating stripe enhancer. In addition, long-range activation results in transcriptional competition at the endogenous eve locus, causing corresponding developmental defects. Overall, we demonstrate that sustained physical proximity and enhancer–promoter engagement are required for enhancer action, and we provide a path to probe the implications of long-range regulation on cellular fates.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)