Liquid biopsy based on 5-hydroxymethylcytosine (5hmC) signatures of plasma cell-free DNA (cfDNA) originating from tumor cells provides a novel approach for early diagnosis in hepatocellular carcinoma ...(HCC). Here, we sought to develop a reliable model using cfDNA 5hmC signatures and protein biomarkers for diagnosis and prognosis of HCC.
We carried out genome-wide 5hmC sequencing of cfDNA samples collected from 165 healthy volunteers, 62 liver cirrhosis (LC) patients and 135 HCC patients. A sensitive 5hmC diagnostic model was developed based on 5hmC signatures selected by sparse Partial Least Squares Discriminant Analysis and cross-validation to define the weighted diagnostic score (wd-score). Then, we combined protein biomarkers with the wd-score to build a more robust score (HCC score) by logistic regression.
The distribution pattern of differential 5hmC regions could clearly distinguish HCC patients, LC patients and healthy volunteers. The wd-score based on 64 5hmC signatures in cfDNA achieves 93.24% of area under the curve (AUC) to distinguish HCC patients from non-HCC patients, and the HCC score by combing protein biomarkers achieves 92.75% of AUC to distinguish HCC patients from LC patients. Meanwhile, the HCC score showed high capacity for screening high recurrence risk patients after receiving surgical resection, and appeared to be an independent indicator for both relapse-free survival (P = 0.00865) and overall survival (P = 0.000739). Furthermore, the values of the HCC score in patients' longitudinal plasma samples were positively associated with tumor burden dynamics during follow-up.
We have developed and validated a novel non-invasive liquid biopsy strategy for HCC diagnosis, prognosis and surveillance during HCC progression.
•A novel liquid biopsy approach was developed for HCC diagnosis, prognosis, and surveillance.•Novel HCC score defined here showed excellent capacity in distinguishing HCC patients from liver cirrhosis patients.•HCC score could predict the early recurrence risk for HCC patients after receiving surgical operation.•HCC score could sensitively monitor tumor burden and progression of HCC in longitudinal.
Spherical LiFe
1−
x
Cr
x
BO
3
/C (
x
= 0, 0.005, 0.008) has been successfully synthesized by ball-milling and spray-drying assisted high-temperature solid-state reaction. The effect of Cr doping on ...LiFeBO
3
/C is characterized by XRD, energy-dispersive X-ray spectroscopy (EDS) and XPS. The results show that LiFe
0.995
Cr
0.005
BO
3
/C delivers the highest initial discharge specific capacity of 196.3 mA h g
−1
at 0.1C and superior rate capability of 90 mA h g
−1
at 5C. Moreover the material presents a cyclic retention of 95% after 50 cycles at 1C. Such improvement in the electrochemical performance can be attributed to the high electronic conductivities (4.75 × 10
−5
S cm
−1
) and Li ion diffusion coefficients (9.20 × 10
−13
cm
2
s
−1
). The introduction of supervalent Cr
3+
into the LiFeBO
3
lattice produces Fe vacancies with accompanying conduction electrons, which lead to the enhanced electronic conductivity and Li ion diffusion coefficient.
Spherical LiFe
1−
x
Cr
x
BO
3
/C (
x
= 0, 0.005, 0.008) has been successfully synthesized by ball-milling and spray-drying assisted high-temperature solid-state reaction.
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•La(Fe,Si)13/La70Co30 were fabricated by low temperature hot-pressing followed by annealing.•With increasing La70Co30 up to 16 wt%, the (σbc)max improved dramatically from 63 to ...352 MPa.•Co atoms from La70Co30 alloy diffused into the 1:13 phase, increasing the TC of the composites.•The MCE of these composites can be adjusted by increasing La70Co30 and prolonging annealing time.
Magnetocaloric composites La(Fe,Si)13/La70Co30 were fabricated by hot-pressing (HP) followed by annealing. With increasing La70Co30 binder content up to 16 wt%, the maximum compressive strength (σbc)max improved dramatically from 63 to 352 MPa. However, the maximum magnetic entropy change (–ΔSM)max decreased from 10.0 to 5.6 Jkg–1K−1 because of the presence of non-magnetic La70Co30. After annealing at 1323 K for 4 h the (σbc)max of HP + Annealed composites with up to 12 wt% La70Co30 doubled compared to HP samples. On the other hand, for a La70Co30 content of 16 wt%, the (σbc)max of HP + Annealed composites decreased slightly compared to that of HP samples, due to reduced α-Fe content and much greater 1:13 phase content in HP + Annealed samples. Remarkably, the (–ΔSM)max of HP + Annealed composites improved from 4.8 to 9.2 Jkg–1K−1 (under 2 T), due to 1:13 phase recombination, after annealing at 1323 K for 4 h.
Objective
The purpose of this work is to investigate the expression of S100A4 and P53 and their correlation with myocardial collagen fibers in hypertrophic cardiomyopathy (HCM).
Patients and methods
...Myocardial tissue obtained from 10 patients undergoing HCM surgery (HCM group) was compared to myocardial tissue obtained from 10 traffic accident deaths (healthy control group). Collagen volume fractions were visualized and compared using sirius red F3B(SR) staining. Immunohistochemistry S-P and in situ hybridization techniques were used to test the different expressions of S100A4, P53 proteins, and their mRNA. Imaging and statistical methods were used for quantitative analysis.
Results
The collagen volume fraction in the HCM group was significantly higher than that in the control group. The integral optical density values of S100A4 and P53 in cardiomyocytes of the HCM group were also significantly higher than in the control group.
Conclusion
The increased content of collagen fibers and overexpression of S100A4 and P53 may play an important role in myocardial fibrosis of HCM, and they can be used in future HCM research. Blockade of S100A4 may have therapeutic potential in HCM by attenuating cardiac fibrosis.
Shine Muscat, with its excellent quality and unique Muscat aroma, is emerging as one of the most profitable table grape cultivars in Asia. However, in-depth analysis of the cultivar's aroma profile ...before berries are harvest-ready is lacking. The aroma components and their concentrations undergo substantial changes during berry ripening, which provides an opportunity for producing some juice/wine products with special flavour. In this study, the evolution of free and bound aroma compounds in Shine Muscat grapes was analysed from EL-35 to EL-38. The main aroma attributes of harvest-ready berries were: 'green', 'sweet', 'floral' and 'fruity'. The headspace SPME-GC-MS analysis revealed that alcohols were the most abundant free and bound compounds in Shine Muscat. Furthermore, the free forms of hexanal, ß-damascenone, and (E, Z)-2,6-nonadienal determined the aroma characteristics of the grapes directly, while the bound forms of ß-damascenone, (E, Z)-2,6-nonadienal, and 2-hexanol determined the aroma of Shine Muscat that cannot to be smelled directly. Taking all indicators together, we believe that picking Shine Muscat grapes at EL-37 (when a minimum TSS of 17% has been reached) maintains its fine aroma characteristics. These results lay the foundation for the further development, utilisation and study of the aroma characteristics of Shine Muscat grapes.
Diverse sources of syndromic surveillance including over-the-counter (OTC) drug sales, hospital and school-based influenza-like illness (ILI) and Baidu search queries estimate influenza activity in ...Tianjin, China. The purpose of this study was to determine which syndromic surveillance systems had the strongest correlation with laboratory-confirmed influenza activity.
Data were obtained from sentinel hospitals and laboratories; sentinel hospitals also reported percentage of ILI. OTC sales and school-based ILI absentee data were provided by public pharmacies and schools. Baidu search queries for influenza surveillance were analyzed. Spearman correlation analysis examined correlations of syndromic systems with laboratory-confirmed data.
Syndromic data for hospital ILI%, OTC sales and school-based ILI correlated well with laboratory data (r = 0.732, 0.490 and 0.693, respectively; P < 0.05). Baidu, the predominant Chinese Internet service, searches for 'influenza', 'cough' and 'fever' correlated best with laboratory-confirmed activity; queries for 'fever' were strongest (r = 0.924, P < 0.001). Correlations between school-based ILI and laboratory-confirmed influenza increased from 0.693 to 0.795 after a 1-week lag (P < 0.05).
A Baidu query of 'fever' provided the strongest correlation to laboratory surveillance. School-based ILI absence reporting detected influenza virus activity 1 week earlier than laboratory confirmation. Use of diverse syndromic surveillance systems in conjunction with traditional surveillance systems can improve influenza surveillance.
A two-level micromechanical model of cortical bone based on a generalized self-consistent method was developed to take into consideration the transversely isotropic elasticity of many microstructural ...features in cortical bone, including Haversian canals, resorption cavities, and osteonal and interstitial lamellae. In the first level, a single osteon was modeled as a two-phase composite such that Haversian canals were represented by elongated pores while the surrounding osteonal lamellae were considered as matrix. In the second level, osteons and resorption cavities were modeled as multiple inclusions while interstitial lamellae were regarded as matrix. The predictions of cortical bone elasticity from this two-level micromechanical model were mostly in agreement with experimental data for the dependence of transversely isotropic elasticity of human femoral cortical bone on porosity. However, variation in cortical bone elastic constants was greater in experimental data than in model predictions. This could be attributed to variations in the elastic properties of microstructural features in cortical bone. The present micromechanical model of cortical bone will be useful in understanding the contribution of cortical bone porosity to femoral neck fractures.
W Jian, L Zhu and X Dong
China General Micro-organism Culture Collection Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, PR China
The partial 60 kDa heat-shock protein ...(HSP60) genes of 36 Bifidobacterium
strains representing 30 different Bifidobacterium species and subspecies
and of the type strain of Gardnerella vaginalis were cloned and sequenced
using a pair of universal degenerate HSP60 PCR primers. The HSP60 DNA
sequence similarities were determined for the taxa at various ranks as
follows: 99.4--100% within the same species, 96% at the subspecies level,
and 73--96% (mean 85%) at the interspecies level (and 98% in the case of
two groups of closely related species, Bifidobacterium animalis and
Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium longum
and Bifidobacterium suis, whose 16S rRNA sequence similarities are all
above 99%). The HSP60 DNA sequence similarities between different
Bifidobacterium species and G. vaginalis, a closely related bacterium
according to 16S rRNA analysis, ranged from 71 to 79% (mean 75%). Although
the topology of the phylogenetic tree constructed using the HSP60 sequences
determined was basically similar to that for 16S rRNA, it seemed to be more
clear-cut for species delineation, and the clustering was better correlated
with the DNA base composition (mol% G+C) than that of the 16S rRNA tree. In
the HSP60 phylogenetic tree, all of the high-G+C (55--67 mol%)
bifidobacteria were grouped into one cluster, whereas the low-G+C species
Bifidobacterium inopinatum (45 mol%) formed a separate cluster with G.
vaginalis (42 mol%) and Bifidobacterium denticolens (55 mol%); a
Bifidobacterium species of intermediate G+C content formed another cluster
between the two. This study demonstrates that the highly conserved and
ubiquitous HSP60 gene is an accurate and convenient tool for phylogenetic
analysis of the genus Bifidobacterium.
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