Dumbbell probe (DP) attracts increasing interests in rolling circle amplification (RCA). A universal DP production method through cleavage-ligation of hairpin was proposed and optimized. The ...production is characterized by restriction endonuclease (RE)-induced cleavage ends ligation. It has the advantage of phosphorylation-free, splint-free and purification-free. To optimize designing, we found that the position of RE cleavage sequence in the stem and the primer position in the loop affected the formation and amplification of DP obviously. Both sticky and blunt ends cleaved by RE produce DP efficiently. Moreover, we introduced this DP into circle to circle (C2C) RCA based on the same cleavage-ligation principle, and acquired high sensitivity. By combining a two-ligation design and the C2C strategy, specificity for detecting let-7 family members was increased extremely. Furthermore, coreaction of different steps facilitated convenient formation and amplification process of DP.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal ...transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether
gene (12190287G/C) variants affect coronary artery disease risk.
We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the
gene was performed.
Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the
gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore,
CC genotypes showed positive correlations with both stable angina and STEMI, whereas
GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with
gene polymorphisms (p for trend < 0.05).
gene polymorphisms may increase susceptibility to stable angina and STEMI.
To determine the survival rate of HIV/AIDS patients after receiving free antiretroviral treatment in Dehong prefecture, Yunnan province.
A retrospective cohort analysis was conducted on all the ...HIV/AIDS patients aged over 16 years who had started antiretroviral treatment during January 2007 throughout December 2009 in Dehong prefecture.
A total of 3103 HIV/AIDS patients had received antiretroviral treatment during the study period. Among them, the mean age was (36.0 ± 9.9) years and 62.4% were males. 66.2% of them were infected with HIV through heterosexual transmission, and the mean treatment follow-up time was 21.7 months. Most patients well complied with the treatment, i.e., the average times of not taking the medicine were less than 5 per month. The cumulative survival rate of antiretroviral treatment after 1, 2, 3, 4, and 5 years were 0.95, 0.94, 0.93, 0.92, and 0.92, respectively. Data from the Cox proportional hazard regression model analysis indicated that, after adjustment for age, gender, and marita
Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with ...glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (
n
= 22) or normal saline placebo (
n
= 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (
p
= 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1
wild type (WT)
TERT
MT
patients, DCV treatment significantly prolonged OS (
p
< 0.01) and PFS (
p
= 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (
p
= 0.02) after DCV treatment. Therefore, IDH1
WT
TERT
MT
and low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Small molecule metabolites and their allosterically regulated repressors play an important role in many gene expression and metabolic disorder processes. These natural sensors, though valuable as ...good logic switches, have rarely been employed without transcription machinery in cells. Here, two pairs of repressors, which function in opposite ways, were cloned, purified and used to control DNA replication in rolling circle amplification (RCA) in vitro. By using metabolites and repressors as inputs, RCA signals as outputs, four basic logic modules were constructed successfully. To achieve various logic computations based on these basic modules, we designed series and parallel strategies of circular templates, which can further assemble these repressor modules in an RCA platform to realize twelve two-input Boolean logic gates and a three-input logic gate. The RCA-output and RCA-assembled platform was proved to be easy and flexible for complex logic processes and might have application potential in molecular computing and synthetic biology.
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A permanently positively charged single-isomer β-CD, mono-6-
N-allylammonium-6-deoxy-β-CD chloride, ALAM-β-CD, has been synthesized and successfully used as chiral selector in capillary ...electrophoresis for enantioseparation of amino acids and dansyl amino acids. The effects of pH, CD's concentration and capillary length on enantioseparation were studied in order to investigate its potential as chiral selector for acidic racemates. By increasing buffer's pH and CD's concentration, fairly robust separations were achieved. Good separations were also obtained with a shorter capillary. In addition, baseline enantiomeric separations of a mixture of six pairs of dansyl
dl-amino acids were achieved under different pH conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses ...challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 μM, with Oxyberberine showing promising effects even at 10 μM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 μM, with Oxyberberine showing promising effects even at 10 μM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Self-powered ultraviolet photodetectors (UVPDs) provide great possibility for the next-generation energy conservation optical communication technology; while the high photodetection performance at ...zero bias is still a tremendous challenge. Herein, n-type GaN film with Si-doping concentration of ~10
18
cm
−3
and p-type organic PEDOT:PSS were adopted to construct a planar hybrid heterojunction via the simple spin-coating method. Profited from typical type-II energy band alignment and giant photovoltaic effect at GaN/PEDOT:PSS inorganic-organic interface, the fabricated UVPD achieved excellent self-powered photoelectrical properties in dual-band with large
R
of 0.96 A/W (2.8 A/W), superior
D
* of 5.7×10
12
Jones (1.7×10
13
Jones), prominent EQE of 325% (1371%), high on/off ratio of 9.65×10
3
(6.15×10
3
) and fast rise/decay time of 60.7/124.5 ms (30.9/26.7 ms) for UVA (UVC) band, as well as outstanding UV/visible rejection ratio and great detection repeatability. Functioned as an optical signal receiver, this designed self-powered UVPD decoded a message of “NJUPT” from a simple optical communication system. These results open a new avenue for GaN/PEDOT:PSS heterojunction in UV communications and related applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Alcoholic cardiomyopathy (ACM) is considered one of the main causes of left ventricular dysfunction and is the leading cause of nonischemic dilated cardiomyopathy (DCM) in developed countries. ...However, very few studies have investigated the relationship between clinical characteristics and prognosis in ACM.
This study aimed to identify risk factors related to a poor outcome in ACM patients.
Retrospective cohort study.
This study included 321 patients with ACM admitted to our hospital between 2003 and 2013. This study aimed to investigate the clinical characteristics and outcomes of the patients with ACM, and the primary endpoint of the study was all-cause mortality, which was assessed through patient medical records (review of patient hospital records and periodic examination of patients in the outpatient clinic) and medical follow-up calls with trained personnel. All-cause mortality was assessed using Kaplan-Meier survival curves, and the risk factors were assessed using Cox regression. A receiver operating characteristic (ROC) curve analysis was performed to optimize the cutoff point for discriminating between the 2 risk groups.
After a median follow-up period of 3.78 years (interquartile range: 2.08-6.52 years), 83 (27.7%) patients were dead. The independent predictors of all-cause mortality due to ACM were the QRS duration (HR: 1.014; 95% CI: 1.004-1.019; P = .003), systolic blood pressure (HR: 0.980; 95% CI: 0.963- 0.997; P = .020), and New York Heart Association classification (HR: 1.595; 95% CI: 1.110-2.290; P = .011) at admission.
Our study indicated that the QRS duration, systolic blood pressure, and New York Heart Association classification at admission provided independent prognostic information in patients with ACM.
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