Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of a diverse array of autoantibodies and the dysfunctional activation of the complement system. The ...specific association between the complement component C3a (C3a) protein and antibodies specific for double-stranded DNA (anti-dsDNA), however, has not been studied in detail to date. This study was thus designed to more fully explore circulating C3a levels in SLE patients. In total, 13 SLE patients were enrolled in this study after having been diagnosed in accordance with the SLICC classification criteria, with 7 and 6 patients respectively exhibiting positivity for anti-dsDNA and anti-Sm autoantibodies. Serum complement component C1q (C1q) and C3a levels in samples from these patients were detected via Western blotting, while other serological, biochemical, and clinical parkers associated with disease activity were detected using standard laboratory techniques. The levels of serum C3a in anti-dsDNA+ patients were significantly elevated as compared to those in anti-Sm+ patients (P < 0.01), and a positive correlation between serum C3a levels and SLE Disease Activity Index scores was detected (P < 0.05, r = 0.6134). C3a levels are correlated with the degree of SLE disease activity and other clinically relevant readouts in SLE patients. C3a levels may also enable the differentiation between inactive and active SLE, while also offering value as an advantageous biomarker for thrombophilia monitoring in SLE patients.
Antimony (Sb), a toxic metalloid, is soluble as antimonate (Sb(V)). While bio-reduction of Sb(V) is an effective Sb-removal approach, its bio-reduction has been coupled to oxidation of only organic ...electron donors. In this study, we demonstrate, for the first time, the feasibility of autotrophic microbial Sb(V) reduction using hydrogen gas (H2) as the electron donor without extra organic carbon source. SEM and EDS analysis confirmed the production of the mineral precipitate Sb2O3. When H2 was utilized as the electron donor, the consortium was able to fully reduce 650 μM of Sb(V) to Sb(III) in 10 days, a rate comparable to the culture using lactate as the electron donor. The H2-fed culture directed a much larger fraction of it donor electrons to Sb(V) reduction than did the lactate-fed culture. While 98% of the electrons from H2 were used to reduce Sb(V) by the H2-fed culture, only 12% of the electrons from lactate was used to reduce Sb(V) by the lactate-fed culture. The rest of the electrons from lactate went to acetate and propionate through fermentation, to methane through methanogenesis, and to biomass synthesis. High-throughput sequencing confirmed that the microbial community for the lactate-fed culture was much more diverse than that for the H2-fed culture, which was dominated by a short rod-shaped phylotype of Rhizobium (α-Protobacteria) that may have been active in Sb(V) reduction.
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•H2 was able to drive the autotrophic bioreduction of Sb(V) as electron donor.•H2 had higher electron utilization efficiency in reducing Sb(V) than lactate.•Lactate-fed culture was much more diverse than that for the H2-fed culture.•The H2-fed culture was dominated by a short rod-shaped phylotype of Rhizobium.
Pre‐eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face ...of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)‐190a‐3p function is tissue‐specific, the precise involvement of miR‐190a‐3p in PE has yet to be determined. We discovered that miR‐190a‐3p was significantly lower and death‐associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target‐regulatory relationship between miR‐190a‐3p and DAPK1. The inhibitory effect of miR‐190a‐3p on autophagy was reversed by co‐transfection of si‐DAPK1 and miR‐190a‐3p inhibitors. Thus, our data indicate that the hypoxia‐dependent miR‐190a‐3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.
Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an ...important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β‐catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β‐catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.
We consider variable selection in high-dimensional sparse multiresponse linear regression models, in which a
q
-dimensional response vector has a linear relationship with a
p
-dimensional covariate ...vector through a sparse coefficient matrix
B
∈
R
p
×
q
. We propose a consistent procedure for the purpose of identifying the nonzeros in
B
. The procedure consists of two major steps, where the first step focuses on the detection of all the nonzero rows in
B
, the latter aims to further discover its individual nonzero cells. The first step is an extension of Orthogonal Matching Pursuit (OMP) and the second step adopts the bootstrap strategy. The theoretical property of our proposed procedure is established. Extensive numerical studies are presented to compare its performances with available representatives.
Abstract
Background
It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study ...investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS).
Methods
Primary GCs were collected from patients with and without PCOS (controls,
n
= 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH,
n
= 30) or without GH treatment (PCOS-C,
n
= 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay.
Results
Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (
P
< 0.05). The mRNA levels of
FOXO1
,
Bax
,
caspase-9
, and
caspase-3
were significantly decreased, whereas
Bcl-2
was increased in GCs of the PCOS-GH group than those in the PCOS-C group (
P
< 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (
P
< 0.05).
Conclusion
OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway.
Clinical trial registration number
Chinese Clinical Trial Registry.
ChiCTR1800019437
. Prospectively registered on October 20, 2018.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Feature selection for the high-dimensional Cox proportional hazards model (Cox model) is very important in many microarray genetic studies. In this paper, we propose a sequential feature selection ...procedure for this model. We define a novel partial profile score to assess the impact of unselected features conditional on the current model, significant features are thereby added into the model sequentially, and the Extended Bayesian Information Criteria (EBIC) is adopted as a stopping rule. Under mild conditions, we show that this procedure is selection consistent. Extensive simulation studies and two real data applications are conducted to demonstrate the advantage of our proposed procedure over several representative approaches.
This study aims to develop a two-stage fluidized catalytic bed reactor system for continuous co-production of carbon nanotubes (CNTs) and hydrogen from waste plastics gasification. Ni/Al-SBA-15 and ...Ni–Cu/CaO–SiO2 catalysts have been synthesized and granulated for CNTs synthesis and hydrogen production in the first- and second-stage reactor, respectively. The operating parameters, including reaction temperature and equivalence ratio (ER), were investigated to confirm the feasibility for CNTs and hydrogen production of this system. The Ni/Al-SBA-15 added in the first-stage reactor enhanced the waste plastics degradation to produce CH4 and C2–C5 hydrocarbons with increasing temperature, which could be used as the source for CNTs synthesis. Lowering the ER promoted the catalytic thermal cracking and reforming of hydrocarbons that contributed to the CNTs and hydrogen production. Nevertheless, the H2 production rate showed a significant increase to 857.6 mmol/h-g catalyst with the assistance of Ni–Cu/CaO–SiO2 in the second-stage reactor. The produced smaller-molecule hydrocarbons from the second-stage reactor with higher temperatures could benefit the co-production of CNTs and hydrogen. The two-stage fluidized catalytic bed gasification system exhibited an optimal performance of high fraction CNTs and H2 when temperatures of first- and second-stage reactor were controlled at 600 and 800 °C, respectively, with 0.1 ER.
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•A two-stage fluidized catalytic bed is developed to produce carbon nanotubes and H2.•Ni/Al-SBA-15 and Ni–Cu/CaO–SiO2 were granulation to use in the pilot-scale system.•Ni/Al-SBA-15 and Ni–Cu/CaO–SiO2 highly enhanced carbon nanotubes and H2 production.•Operating parameters of the fluidized bed were evaluated for catalytic performance.•The system gave 857.6 mmol H2/h-g catalyst and carbon nanotubes fraction of 48.0%.
Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role ...NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.
Association of Coagulation factor V (F5) polymorphisms with the occurrence of many types of cancers has been widely reported, but whether it is of prognostic relevance in some cancers remain to be ...resolved. The RNA-sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA). The potential of F5 genes to predict the survival time of gastric cancer (GC) patients was investigated using univariate and multivariate survival analysis whereas “Kaplan-Meier plotter” (KM-plotter) online tools were employed to validate the outcomes. TCGA data revealed that F5 mRNA levels were significantly upregulated in gastric cancer samples. Survival analysis confirmed that high levels of F5 mRNA correlated with short overall survival (OS) in gastric cancer patients, and the area under the curve (AUC) values of 1-, 2-, and 5-year OS rate were 0.554, 0.593, and 0.603, respectively. Survival analysis by KM-plotter indicated that the high expression of F5 mRNA was significantly associated with a shorter OS compared with the low expression level in all patients with GC, and this was also the case for patients in stage III (hazard ratio HR=1.78, P=0.017). These findings suggest that the F5 gene is significantly upregulated in GC tumour tissues, and may be a potential prognostic biomarker for GC.
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