Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of ...serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection.
Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed.
The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863.
Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.
The phase separation behavior of mixed solution of caseinate (Cas) and alginate (Alg) was investigated. Lactobacillus plantarum FZU3013 was encapsulated using 4 % Cas/1 % Alg gel beads with a ...phase-separated structure. The bacteria were predominantly distributed in the Alg-rich continuous phase. The use of 4 % Cas/1 % Alg beads resulted in higher encapsulation efficiency for L. plantarum FZU3013 compared to 1 % Alg beads. After 5 weeks of storage at 4 °C, the viable count in 4 % Cas/1 % Alg beads was 8.3 log CFU/g, which was 1.1 log CFU/g higher than that of the 1 % Alg beads. When 1 % Alg beads of the smallest size were subjected to in vitro digestion, no viable bacteria could be detected at the end of the digestion, whereas the 4 % Cas/1 % Alg beads of the smallest size had a viable count of 3.9 log CFU/g. When the size of the 4 % Cas/1 % Alg beads was increased to 1000 μm, the viable count was 7.0 log CFU/g after digestion. The results of infrared spectroscopy and zeta potential indicated that hydrogen bonding and electrostatic interactions between caseinate and alginate reinforced the structure of the gel beads and improved the protection for L. plantarum FZU 3013.
Tenascin‐c is an extracellular matrix glycoprotein, the expression of which relates to the progression of atherosclerosis, myocardial infarction and heart failure. Annexin II acts as a cell surface ...receptor of tenascin‐c. This study aimed to delineate the role of tenascin‐c and annexin II in macrophages presented in atherosclerotic plaque. Animal models with atherosclerotic lesions were established using ApoE‐KO mice fed with high‐cholesterol diet. The expression of tenascin‐c and annexin II in atherosclerotic lesions was determined by qRT‐PCR, Western blot and immunohistochemistry analysis. Raw 264.7 macrophages and human primary macrophages were exposed to 5, 10 and 15 μg/ml tenascin‐c for 12 hrs. Cell migration as well as the proangiogenic ability of macrophages was examined. Additionally, annexin II expression was delineated in raw 264.7 macrophages under normal condition (20% O2) for 12 hrs or hypoxic condition (1% O2) for 6–12 hrs. The expression of tenascin‐c and annexin II was markedly augmented in lesion aorta. Tenascin‐c positively regulated macrophage migration, which was dependent on the expression of annexin II in macrophages. VEGF release from macrophages and endothelial tube induction by macrophage were boosted by tenascin‐c and attenuated by annexin II blocking. Furthermore, tenascin‐c activated Akt/NF‐κB and ERK signalling through annexin II. Lastly, hypoxia conditioning remarkably facilitates annexin II expression in macrophages through hypoxia‐inducible factor (HIF)‐1α but not HIF‐2α. In conclusion, tenascin‐c promoted macrophage migration and VEGF expression through annexin II, the expression of which was modulated by HIF‐1α.
Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ...However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss–related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN HLA chimerism for loss of heterozygosity (LOH) analysis by NGS, was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss–related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort odds ratio (OR): 3.15, P = 0.021 and patients with myeloid malignancies (OR: 3.94, P = 0.021). A higher refined-disease risk index (OR: 6.91, P = 0.033) and donor–recipient ABO incompatibility (OR: 4.58, P = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.
Key message
A major resistance QTL was identified on chromosome 6 in rice variety Wuke; both overexpression and knockdown experiments confirmed that
OsGLK1
is the candidate gene for association with
...Rice black-streaked dwarf virus
disease.
Rice black-streaked dwarf virus disease is one of the most destructive rice viral diseases in China and East Asia. Progress has been limited in RBSDVD resistance breeding due to inadequate knowledge on the underlying functional genes. In this study, a major QTL for RBSDV (rice black-streaked dwarf virus) independent of SBPH (small brown planthopper) resistance was mapped in a 1.8 Mb interval on chromosome 6 by using an F
2:3
population originated from resistant rice variety Wuke. Representative transcripts within this region were analysed and three genes showing amino acid sequence variation in functional domains were selected for transformation. Overexpression experiments showed that one gene exhibited significant enhanced resistance compared to control lines, encoding protein involving Myb domain and probable transcription factor Golden 2-like1 (GLK1). Furthermore,
OsGLK1
knockdown rice lines were investigated and the resistance ability was significantly declined without this gene compared to the wild type. Taken together, both overexpression and knockdown experiments strongly suggested that
OsGLK1
plays an important role for RBSDV resistance and contributes to the major QTL. The study paves the way for elucidating the molecular mechanism underlying RBSDVD resistance and the molecular markers associated with
OsGLK1
may be used for marker-assisted selection.
The inappropriate use of antibiotics has led to the emergence of multidrug-resistant strains. Bacteriophages (phages) have gained renewed attention as promising alternatives or supplements to ...antibiotics. In this study, a lytic avian pathogenic
Escherichia coli
(APEC) phage designated as PEC9 was isolated and purified from chicken farm feces samples. The morphology, genomic information, optimal multiplicity of infection (MOI), one-step growth curve, thermal stability, pH stability,
in vitro
antibacterial ability and biofilm formation inhibition ability of the phage were determined. Subsequently, the therapeutic effects of the phages were investigated in the mice model. The results showed that PEC9 was a member of the siphovirus-like by electron microscopy observation. Biological characterization revealed that it could lyse two serotypes of
E. coli
, including O1 (9/20) and O2 (6/20). The optimal multiplicity of infection (MOI) of phage PEC9 was 0.1. Phage PEC9 had a latent period of 20 min and a burst period of 40 min, with an average burst size of 68 plaque-forming units (PFUs)/cell. It maintained good lytic activity at pH 3-11 and 4-50°C and could efficiently inhibit the bacterial planktonic cell growth and biofilm formation, and reduce bacterial counts within the biofilm, when the MOI was 0.01, 0.1, and 1, respectively. Whole-genome sequencing showed that PEC9 was a dsDNA virus with a genome of 44379 bp and GC content of 54.39%. The genome contains 56 putative ORFs and no toxin, virulence, or resistance-related genes were detected. Phylogenetic tree analysis showed that PEC9 is closely related to
E. coli
phages vB_EcoS_Zar3M, vB_EcoS_PTXU06, SECphi18, ZCEC10, and ZCEC11, but most of these phages exhibit different gene arrangement. The phage PEC9 could successfully protect mice against APEC infection, including improved survival rate, reduced bacterial loads, and organ lesions. To conclude, our results suggest that phage PEC9 may be a promising candidate that can be used as an alternative to antibiotics in the control of APEC infection.
Multifunctional drug delivery carriers have emerged as a promising cancer drug delivery strategy. Here, we developed a vitamin E succinate-chitosan-histidine (VCH) multi-program responsive drug ...carrier. The structure was characterized by FT-IR and 1H NMR spectrum, and the DLS and SEM results showed typical nanostructures. The drug loading content was 21.0 % and the corresponding encapsulation efficiency was 66.6 %. The UV–vis and fluorescence spectra demonstrated the existence of the π-π stacking interaction between DOX and VCH. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/VCH nanoparticles could be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate was up to 56.27 %. The DOX/VCH reduced the tumor volume and weight efficiently with a TIR of 45.81 %. The histological analysis results showed that DOX/VCH could effectively inhibit tumor growth and proliferation, and there was no damage to normal organs. VCH nanocarriers could combine the advantages of VES, histidine and chitosan to achieve pH sensitivity and P-gp inhibition, and effectively improve the drug solubility, targeting and lysosomal escape. Through the program response of different micro-environment, the newly developed polymeric micelles could successfully be utilized as a multi-program responsive nanocarrier system for the treatment of cancers.
Schematic diagram of the VCH nanoparticles structure and its anticancer effect. Display omitted
•A multifunctional drug delivery carrier (VCH) was fabricated by use of vitamin E succinate, chitosan and histidine.•The VCH showed good cytocompatibility, hemocompatibility, tissue compatibility, and drug load contents.•The VCH was microenvironment responsive, including pH sensitivity and mitochondrial targeting ability.•The DOX/VCH reduced the tumor growth efficiently with a TIR of 45.81 % in vivo.
Cryogenic CO
2
-assisted minimum quantity lubrication milling technology is a green processing technology with broad application prospects. Aiming at the problem of tool wear in the application of ...cryogenic CO
2
-assisted minimum quantity lubrication in difficult-to-machine materials and the influence of relevant parameters on tool wear, this study used coated cemented carbide tools to perform milling experiments under cryogenic CO
2
-assisted minimum quantity lubrication technology conditions. The micro-morphology of the tool and chip was observed, and the energy spectrum of the tool chip contact area was analyzed. The results show that reducing CO
2
temperature and increasing the oil flow of minimum quantity lubrication can improve the tool wear. The tool wear mechanisms under cryogenic CO
2
-assisted minimum quantity lubrication are mainly abrasive wear, diffusion wear, and oxidation wear. The chip sawtooth degree of the optimal parameter group is more conducive to chip breaking than that of dry-cutting and wet-cutting groups. The temperature of the tool-chip contact area is an important factor affecting tool wear; the higher the temperature, the faster the tool wear. At the same time, it is verified that cryogenic CO
2
-assisted minimum quantity lubrication technology can replace cutting fluid in hard-to-machine materials under certain conditions.
Classification of Alzheimer's Disease (AD) has been becoming a hot issue along with the rapidly increasing number of patients. This task remains tremendously challenging due to the limited data and ...the difficulties in detecting mild cognitive impairment (MCI). Existing methods use gait or EEG (electroencephalogram) data only to tackle this task. Although the gait data acquisition procedure is cheap and simple, the methods relying on gait data often fail to detect the slight difference between MCI and AD. The methods that use EEG data can detect the difference more precisely, but collecting EEG data from both HC (health controls) and patients is very time-consuming. More critically, these methods often convert EEG records into the frequency domain and thus inevitably lose the spatial and temporal information, which is essential to capture the connectivity and synchronization among different brain regions. This paper proposes a cascade neural network with two steps to achieve a faster and more accurate AD classification by exploiting gait and EEG data simultaneously. In the first step, we propose attention-based spatial temporal graph convolutional networks to extract the features from the skeleton sequences (i.e., gait) captured by Kinect (a commonly used sensor) to distinguish between HC and patients. In the second step, we propose spatial temporal convolutional networks to fully exploit the spatial and temporal information of EEG data and classify the patients into MCI or AD eventually. We collect gait and EEG data from 35 cognitively health controls, 35 MCI, and 17 AD patients to evaluate our proposed method. Experimental results show that our method significantly outperforms other AD diagnosis methods (91.07 vs. 68.18%) in the three-way AD classification task (HC, MCI, and AD). Moreover, we empirically found that the lower body and right upper limb are more important for the early diagnosis of AD than other body parts. We believe this interesting finding can be helpful for clinical researches.
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