Purpose
MicroRNAs are small, non-coding RNAs that are critical regulators of various diseases including cancer, and may represent a novel class of cancer biomarkers. Recent reports have highlighted ...the oncogenic aspects of
miR
-
125b
. However, the level and clinical relevance of circulating
miR
-
125b
transcripts in human serum of non-small-cell lung cancer (NSCLC) patients are unclear. The purpose of this study was to identify circulating
miR
-
125b
transcripts in human serum for use as a biomarker for stratification and prediction of prognosis in NSCLC.
Methods
We analyzed serum levels of
miR
-
125b
in 193 patients with different stages of NSCLC. Blood samples were collected before surgery and therapy. Quantitative reverse transcription–polymerase chain reaction of circulating
miR
-
125b
transcripts was performed directly in serum to improve the efficiency of miRNA assessment. Receiver operating characteristic analysis was used to evaluate the sensitivity and specificity of serum
miR
-
125b
.
Results
We found that serum
miR
-
125b
was consistently expressed in the non-tumor group and was significantly associated with NSCLC stage.
miR
-
125b
expression was capable of separating NSCLC patients from control groups with an area under the curve of 0.786. Furthermore, patients with high
miR
-
125b
expression displayed a significantly poorer prognosis compared with patients with low expression (
p
< 0.0001). Multivariate analysis indicated that high
miR
-
125b
expression was an independent prognostic factor for survival.
Conclusions
We propose that serum
miR
-
125b
may represent a novel biomarker in NSCLC patients and that high
miR
-
125b
expression is an independent prognostic factor for survival.
Display omitted
•A machine learning based strategy was proposed to improve the processing fidelity of the vat polymerization process by automatically tuning the distribution of localized grey-pixels ...of different intensities.•A chessboard pattern based data generation and training strategy was proposed to help the model better understand the impact of curing resulting from different combinations of adjoining greyscale pixel levels.•An automated data processing strategy to help extract and repair data after data collection.•The introducing of CGAN system for increasing the sets of training data.
Like many pixel-based additive manufacturing (AM) techniques, digital light processing (DLP) based vat photopolymerization faces the challenge that the square pixel based processing strategy can lead to zigzag edges especially when feature sizes come close to single-pixel levels. Introducing greyscale pixels has been a strategy to smoothen such edges, but it is a challenging task to understand which of the many permutations of projected pixels would give the optimal 3D printing performance. To address this challenge, a novel data acquisition strategy based on machine learning (ML) principles is proposed, and a training routine is implemented to reproduce the smallest shape of an intended 3D printed object. Through this approach, a chessboard patterning strategy is developed along with an automated data refining and augmentation workflow, demonstrating its efficiency and effectiveness by reducing the deviation by around 30%.
Objectives. The objective of this study is to unravel the correlation between RDW and the severity and prognosis of CAP, as well as exploring RDW with the inflammatory markers white blood cells ...(WBC), C-reactive protein (CRP), and procalcitonin (PCT). Methods. According to the data characteristics, appropriate statistical methods were selected to analyze the relationship between RDW and the severity and prognosis of CAP patients and to determine whether RDW is associated with the inflammatory markers WBC, CRP, and PCT. Results. The results show that with the increase of PSI and CURB-65 values, the proportion of patients with RDW ≥ 12.987% is significantly higher than that of RDW < 12.987% (P<0.01). When RDW is combined with PSI or CURB-65 to predict the 90-day mortality of CAP patients, the area under the receiver operating characteristic (ROC) curve increased prominently, and if RDW, PSI, and CURB-65 are combined, the area under the ROC curve is maximized. Conclusions. Our findings suggest that the higher RDW value is associated with short-term adverse outcomes in CAP patients. We also find that when RDW, PSI, and CURB-65 are combined, the best performance is achieved to predict CAP 90-day mortality risk.
ABSTRACTSingle-nozzle based multimaterial direct ink writing enables voxel-based fabrication with superior printing efficiency than multi-nozzle protocol. This is attractive for food 3D printing ...process where efficiency matters for its application. However, for single-nozzle based process, the presence of residual material in the shared channel can affect its printing fidelity. In this study, we propose a path planning algorithm that can address this issue by incorporating (i) advance distance to compensate the extrusion delay when switching materials, and (ii) in-process printhead motion adjustments to stabilise the extrusion process. Our approach demonstrated a substantial improvement in printing fidelity, where the switching point offset was reduced to ±0.5 mm. Similarly, the unstable extrusion behaviours (bulging and necking) during switching materials were suppressed, where the printing fidelity was improved by 27 ± 5% (bulging) and 19 ± 3% (necking) respectively. Additionally, we provide an open-source slicing programme that empowers users to implement the above two algorithms.
Lignocellulose is the most abundant natural biomass resource for the production of biofuels and other chemicals. The efficient degradation of cellulose by cellulases is a critical step for the ...lignocellulose bioconversion. Understanding the structure-catalysis relationship is vital for rational design of more stable and highly active enzymes. Glycoside hydrolase (GH) family 5 is the largest and most functionally diverse group of cellulases, with a conserved TIM barrel structure. The important roles of the various loop regions of GH5 enzymes in catalysis, however, remain poorly understood. In the present study, we investigated the relationship between the loops surrounding active site architecture and its catalytic efficiency, taking TfCel5A, an enzyme from GH5_2 subfamily of Thermobifida fusca, as an example. Large-scale computational simulations and site-directed mutagenesis experiments revealed that three loops (loop 8, 3, and 7) around active cleft played diverse roles in substrate binding, intermediate formation, and product release, respectively. The highly flexible and charged residue triad of loop 8 was responsible for capturing the ligand into the active cleft. Severe fluctuation of loop 3 led to the distortion of sugar conformation at the - 1 subsite. The wobble of loop 7 might facilitate product release, and the enzyme activity of the mutant Y361W in loop 7 was increased by approximately 40%. This study unraveled the vital roles of loops in active site architecture and provided new insights into the catalytic mechanism of the GH5_2 cellulases.
In this paper, an energy regulation method based on the combination of a half-wave plate (HWP) and a polarization beam splitter (PBS) is proposed for the fabrication of apodized fiber gratings, which ...can effectively improve the side lobe suppression ratio of high-reflectivity fiber Bragg gratings (FBGs) fabricated by femtosecond laser. The apodized FBGs prepared by this method has good repeatability and flexibility. By inputting different types of apodization functions through the program, the rotation speed of the stepping motor can be adjusted synchronously, and then the position of the HWP can be accurately controlled so that the laser energy can be distributed as an apodization function along the axial direction of the fiber. By using the energy apodization method, the gratings with a reflectivity of 75% and a side lobe suppression ratio of 25 and 32 dB are fabricated in the fiber with a core diameter of 9 and 4.4 μm, respectively. The temperature and strain sensitivities of the energy-apodized fiber gratings with a core diameter of 4.4 μm are 10.36 pm/°C and 0.9 pm/με, respectively. The high-reflectivity gratings fabricated by this energy apodization method are expected to be used in high-power narrow-linewidth lasers and wavelength division multiplexing (WDM) systems.
In this paper, a sapphire-derived fiber (SDF) with a core diameter of 10 μm and a cladding diameter of 125 μm is fabricated by the melt-in-tube method, and fiber Bragg gratings (FBGs) with ...reflectivity over 80% are prepared by the femtosecond laser point-by-point direct writing method. By analyzing the refractive index distribution and reflection spectral characteristics of the SDF, it can be seen that the SDF is a graded refractive index few-mode fiber. In order to study the element composition of the SDF core, the end-face element distribution of the SDF is analyzed, which indicates that element diffusion occurred between the core and the cladding materials. The temperature and stress of the SDF gratings are measured and the highest temperature is tested to 1000 °C. The temperature and strain sensitivities are 15.64 pm/°C and 1.33 pm/με, respectively, which are higher than the temperature sensitivity of the quartz single-mode fiber. As a kind of special fiber, the SDF expands the application range of sapphire fiber, and has important applications in the fields of high-temperature sensing and high-power lasers.
XynB from
Aspergillus niger
ATCC1015 (
An
XynB) is a mesophilic glycoside hydrolase (GH) family 11 xylanase which holds great potentials in a wide variety of industrial applications. In the present ...study, the catalytic activity and stability of
An
XynB were improved by a combination of computational and experimental approaches. Virtual mutation and molecular dynamics simulations indicated that the introduction of Glu and Asn altered the interaction network at the − 3 subsite. Interestingly, the double mutant S41N/T43E displayed 72% increase in catalytic activity when compared to the wild type (WT). In addition, it also showed a better thermostability than the WT enzyme. Kinetic determination of the T43E and S41N/T43E mutants suggested that the higher xylanase activity is probably due to the increasing binding affinity of enzyme and substrate. Consequently, the enzyme activity and thermostability of
An
XynB was both increased by selective site-directed mutagenesis at the − 3 subsite of its active site architecture which provides a good example for a successfully engineered enzyme for potential industrial application. Moreover, the molecular evolution approach adopted in this study led to the design of a library of sequences that captures a meaningful functional diversity in a limited number of protein variants.
To explore the role of genetic polymorphisms of bone morphogenic proteins 4 (BMP-4) in the response to platinum-based chemotherapy and the clinical outcome in patients with advanced nonsmall cell ...lung cancer (NSCLC), 938 patients with stage III (A+B) or IV NSCLC were enrolled in this study. We found that the variant genotypes of 6007C > T polymorphisms significantly associated with the chemotherapy response. The 6007CC genotype carriers had a higher chance to be responder to chemotherapy (adjusted odd ratio = 2.77; 95% CI: 1.83–4.18; adjusted < 0.001). The 6007C > T polymorphisms and BMP-4 expression also affect the prognosis of NSCLC. Patients with high BMP-4 expression had a significantly higher chance to be resistant to chemotherapy than those with low BMP-4 expression (OR = 2.81; 95% CI: 1.23–6.44; P = 0.01 ). The hazard ratio (HR) for 6007TT was 2.37 times higher than 6007CC ( P = 0.003 ). In summary, the 6007C > T polymorphism of BMP-4 gene and BMP-4 tissue expression may be used as potential predictor for the chemotherapy response and prognosis of advanced NSCLC.
The biodegradation of chitin is an important part of the carbon and nitrogen cycles in nature. Speeding up the biotransformation of chitin substrates can not only reduce pollution, but also produce ...high value-added products. However, this process is strictly regulated by the catalytic efficiency of the chitinolytic machinery. Therefore, it is necessary to study the mode of action and compound mechanisms of different chitin-degrading enzymes in depth to improve the catalytic efficiency of the chitinolytic machinery.
The thermophilic bacterium
sp. F-3 showed comparatively high chitin degradation activities. To elucidate the mechanism underlying chitin hydrolysis, six chitin degradation-related enzymes were identified in the extracellular proteome of
sp. F-3, including three chitinases (
Chi18A,
Chi18B, and
Chi18C) from the GH18 family, one GH19 chitinase (
Chi19A), one GH20 β-
-acetylhexosaminidase (
GH20A), and one lytic polysaccharide monooxygenase (
LPMO10A) from the AA10 family. All were upregulated by chitin. The heterologously expressed hydrolases could withstand temperatures up to 70 °C and were stable at pH values of 4 to 11. Biochemical analyses displayed that these chitin degradation-related enzymes had different functions and thus showed synergistic effects during chitin degradation. Furthermore, based on structural bioinformatics data, we speculated that the different action modes among the three GH18 chitinases may be caused by loop differences in their active site architectures. Among them,
Chi18A is probably processive and mainly acts on polysaccharides, while
Chi18B and
Chi18C are likely endo-non-processive and displayed higher activity on the degradation of chitin oligosaccharides. In addition, proteomic data and synergy experiments also indicated the importance of
LPMO10A, which could promote the activities of the hydrolases and increase the monosaccharide content in the reaction system, respectively.
In this article, the chitinolytic machinery of a thermophilic
species was studied to explore the structural basis for the synergistic actions of chitinases from different GH18 subfamilies. The elucidation of the degradation mechanisms of these thermophilic chitinases will lay a theoretical foundation for the efficient industrialized transformation of natural chitin.
PDF
