Multiplexed Serum Biomarkers for the Detection of Lung Cancer

AbstractCurrently, there is no available biomarker for lung cancer diagnosis. Here we recruited 844 lung cancer patients and 620 healthy participants from six hospitals. A total of four serum proteins was identified and subsequently assessed in the training and validation cohorts. The concentrations of four serum proteins were found to be significantly higher in lung cancer patients compared with healthy participants. The area under the curve (AUC) for the 4-biomarker were 0.86 in the training cohort, and 0.87 in the validation cohort. The classification improved to a corrected AUC of 0.90 and 0.89 respectively following addition of sex, age and smoking status. Similar results were observed for early-stage lung cancer. Remarkably, in a blinded test with a suspicious pulmonary nodule, the adjusted prediction model correctly discriminated the patients with 86.96% sensitivity and 98.25% specificity. These results demonstrated the 4-biomarker panel improved lung cancer prediction beyond that of known risk factors. Moreover, the biomarkers were valuable in differentiating benign nodules which will remain indolent from those that are likely to progress and therefore might serve as an adjuvant diagnosis tool for LDCT scanning

Synergistic adsorption of Cd(II) with sulfate/phosphate on ferrihydrite: An in situ ATR-FTIR/2D-COS study

Elucidation of the co-adsorption characteristics of heavy metal cations and oxyanions on (oxyhydr)oxides can help to better understand their distribution and transformation in many geological settings. In this work, batch adsorption experiments in combination with in situ attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were applied to explore the interaction mechanisms of Cd(II) with sulfate or phosphate at the ferrihydrite (Fh)–water interface, and the two-dimensional correlation spectroscopic analysis (2D–COS) was used to enhance the resolution of ATR-FTIR bands and the accuracy of analysis. The batch adsorption experiments showed enhanced adsorption of both sulfate (S) and phosphate (P) on Fh when co-adsorbed with Cd(II); additionally, the desorbed percentages of Cd(II) were much lower in the P + Cd adsorption systems than those in the S + Cd adsorption systems. The spectroscopic results suggested that in the single adsorption systems, sulfate primarily adsorbed as outer-sphere complexes with a small amount of bidentate inner-sphere complexes, while the dominant adsorbed species of phosphate were largely the bidentate nonprotonated inner-sphere complexes, although there was significant pH-dependence. In the co-adsorption systems, the synergistic adsorption of Cd(II) and sulfate was dominantly attributed to the electrostatic interaction, as well as the formation of Fe–Cd–S (i.e., Cd-bridged) ternary complexes. In contrast, Fe–P–Cd (i.e., phosphate-bridged) ternary complexes were found in all of the co-adsorption systems of phosphate and Cd(II); furthermore, electrostatic interaction should also contribute to the co-adsorption process. Our results show that in situ ATR-FTIR in combination with 2D–COS can be an efficient tool in analyzing the co-adsorption mechanisms of anions and heavy metal cations on iron (oxyhydr)oxides in ternary adsorption systems. The co-existence of Cd(II) with sulfate or phosphate can be beneficial for their accumulations on Fh, and phosphate is more efficient than sulfate for the long-term immobilization of Cd(II)

Pseudouridylation (Ψ) of U2 snRNA in S.cerevisiae is catalyzed by an RNA-independent mechanism

Pseudouridylation of snRNAs in vertebrates is guided by small nucleolar/Cajal body-specific RNAs (sno/scaRNAs). We developed an in vitro system using cell extracts and single site-radiolabeled U2 snRNAs to study pseudouridylation in Saccharomyces cerevisiae. Micrococcal nuclease-treated cell extracts are fully competent to catalyze U2 pseudouridylation, suggesting an RNA-independent process. A pseudouridylase activity for Ψ(35) within yeast U2 is identified via a screen of an S.cerevisiae GST–ORF protein library. This activity is associated with YOR243c ORF, which has not previously been assigned function. When the GST–YOR243c protein is expressed in Escherichia coli, pseudouridylation activity is comparable to that expressed in S.cerevisiae, demonstrating that this protein (designated Pus7) alone can catalyze Ψ(35) formation in U2. Both in vitro and in vivo analyses using wild-type and pus7-Δ strains show that Pus7 is indispensable for Ψ(35) formation in U2. Using site-specific radiolabeled U2 and U2 fragments, we show that Pus7 activity is specific for Ψ(35) and that the U2 stem– loop II region is essential for the pseudouridylation reaction. A BLAST search revealed Pus7 homologs in various organisms

Comparative Study on Drying Characteristics and Quality of Apple Cubes Dried in Two Different Microwave Dryers

A rotary plate microwave dryer (RMD) and a newly-developed microwave convection coupled dryer (MCD) were used to dry apple cubes. The effects of microwave output power on drying, heating characteristics and quality attributes including scorching rate, color parameters, rehydration ratio, shrinkage, hardness, and sensory scores of the apple cubes were investigated and compared. The results showed that the microwave power required to complete drying in RMD was only 1/6 of that in MCD at the same microwave power density. Total drying time was 120, 60 and 30 min at 70, 210 and 350 W in RMD, respectively, while 160, 90, 80 and 60 min at 400; 800; 1,200; and 1,600 W in MCD, respectively. Compared with the products dried using hot air, the apple cubes dried in both dryers at the low microwave power had better rehydration capacity, less shrinkage and lower hardness as well as a* and b* value of color. Application of microwave power of over 800 W in MCD and over 210 W in RMD caused the increase in scorching rate as well as decreased the L* value and the sensory quality of the apple cubes. Microwave drying in MCD with temperature control improved the quality of the dried product. The microwave drying conditions suitable for the apple cubes were 400 W in MCD and 1,600 W in MCD with temperature control followed by 70 W in RMD; the products obtained under these three condition variants had superior or comparable quality to the products obtained upon conventional hot air-drying

Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention

AbstractDiabetic kidney disease (DKD) is a common complication of diabetes and has become the leading cause of end-stage kidney disease. The pathogenesis of DKD is complicated, and oxidative stress is considered as a core of DKD onset. High glucose can lead to increased production of reactive oxygen species (ROS) via the polyol, PKC, AGE/RAGE and hexosamine pathways, resulting in enhanced oxidative stress response. In this way, pathways such as PI3K/Akt, TGF-β1/p38-MAPK and NF-κB are activated, inducing endothelial cell apoptosis, inflammation, autophagy and fibrosis that cause histologic and functional abnormalities of the kidney and finally result in kidney injury. Presently, the treatment for DKD remains an unresolved issue. Traditional Chinese medicine (TCM) has unique advantages for DKD prevention and treatment attributed to its multi-target, multi-component, and multi-pathway characteristics. Numerous studies have proved that Chinese herbs (e.g., Golden Thread, Kudzuvine Root, Tripterygium glycosides, and Ginseng) and patent medicines (e.g., Shenshuaining Tablet, Compound Rhizoma Coptidis Capsule, and Zishen Tongluo Granule) are effective for DKD treatment. The present review described the role of oxidative stress in DKD pathogenesis and the effect of TCM intervention for DKD prevention and treatment, in an attempt to provide evidence for clinical practice

Insulin-Like Growth Factor-1 Signaling in Lung Development and Inflammatory Lung Diseases

Insulin-like growth factor-1 (IGF-1) was firstly identified as a hormone that mediates the biological effects of growth hormone. Accumulating data have indicated the role of IGF-1 signaling pathway in lung development and diseases such as congenital disorders, cancers, inflammation, and fibrosis. IGF-1 signaling modulates the development and differentiation of many types of lung cells, including airway basal cells, club cells, alveolar epithelial cells, and fibroblasts. IGF-1 signaling deficiency results in alveolar hyperplasia in humans and disrupted lung architecture in animal models. The components of IGF-1 signaling pathways are potentiated as biomarkers as they are dysregulated locally or systemically in lung diseases, whereas data may be inconsistent or even paradoxical among different studies. The usage of IGF-1-based therapeutic agents urges for more researches in developmental disorders and inflammatory lung diseases, as the majority of current data are collected from limited number of animal experiments and are generally less exuberant than those in lung cancer. Elucidation of these questions by further bench-to-bedside researches may provide us with rational clinical diagnostic approaches and agents concerning IGF-1 signaling in lung diseases