Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, ...single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed.
Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this ...study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles.
Tremendous amounts of nitrogen (N) fertilizer have been added to arable lands, often resulting in substantial effects on terrestrial ecosystems, including soil acidification, altered enzyme ...activities and changes in microbial community composition. Soil microbes are the major drivers of soil carbon (C) and N cycling; therefore, understanding the response of microbial communities to elevated N inputs is of significant importance. This study was carried out to investigate the influences of different N fertilization rates (0, 182, and 225 kg ha-1 representing control, low, and high N supply for each crop season for summer maize and winter wheat) on soil biochemical attributes, extracellular enzyme activities, and the microbial community composition in a winter wheat-summer maize rotation cropping system in north-central China. The results showed that N addition significantly decreased the soil pH in both the wheat and maize seasons. Microbial biomass N (MBN) decreased following N fertilization in the wheat season, while the opposite trend in MBN was observed in the maize season. Response ratio analysis showed that the activities of enzymes involved in C, N, and phosphorus cycling were significantly enhanced under N enrichment in both the wheat and maize seasons, and higher enzyme activities were noted in the high N addition treatment than in the low N addition treatment. A linear increase in fungal abundance with the N addition gradient was observed in the wheat season, whereas the fungal abundance increased and then decreased in the maize season. The bacterial abundance showed an increased and then decreased trend in response to the N addition gradient in both the wheat and maize crop seasons. Moreover, the partial least squares path model (PLS-PM) analysis showed that soil pH and soil organic carbon (SOC) were the most important soil variables, causing shifts in the soil bacteria. Furthermore, compared with the N-cycling enzymes, the C-cycling enzymes were significantly affected by the soil pH and SOC. Taken together, these results suggest that the effect of N addition on enzyme activities was consistent in both crop seasons, while the effects on MBN and microbial community composition to N addition were highly variable in the two crop seasons. Moreover, N fertilization-induced changes in the soil chemical properties such as soil acidity and SOC played a substantial role in shaping the microbial community.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The flow stress behavior and corrosive properties of Al-7Si alloy were studied by thermal compression test, electrochemical test, and electron probe microanalysis. The influences of temperatures, ...strain rates, strains, and morphology of Si particles on stress-strain curves of Al-7Si alloy were analyzed. The peak stress of unmodified-Al-7Si alloy is higher than that of Sr-modified-Al-7Si alloy at the same deformation conditions, and the phenomenon is obviously relevant to the distribution and morphology of Si particles. The morphology of Si particles of unmodified-undeformed-Al-7Si alloy is a typical thick layer, and that of unmodified-deformed-Al-7Si alloy is broken into relatively small particles and the distribution is relatively even in homogeneous deformation zone II. The distribution of Si particles in Sr-modified-deformed-Al-7Si alloy is obviously more even than undeformed alloy. The effect of a small deformation of 20% on the distribution and morphology of Si particles is obviously smaller than that of a large deformation of 50%. The electrochemical self-corrosion potential of Sr-modified-Al-7Si alloy is higher than that of unmodified-Al-7Si alloy, and it proves that the distribution and morphology of Si particles have a certain influence on the corrosive properties of Al-7Si alloy. That is, the even fine Si particles are more conducive to improving the corrosive properties of Al-7Si alloy.
Hepatic steatosis is the early stage of alcoholic liver disease (ALD), may progress to steatohepatitis, fibrosis even cirrhosis. Polydatin, the primary active component of Polygonum cuspidatum Sieb. ...et Zucc, has been recognized to possess hepatoprotective and anti-inflammatory properties. To investigate whether polydatin alleviates ethanol induced liver injury and to elucidate the underlying molecular mechanisms, zebrafish larvae at 4 days post-fertilization (dpf) were exposed to 350 mmol/L of ethanol for 32 h, then treated with polydatin for 48 h. Oil red O, Nile Red and H&E staining were used to analyze the pathological changes in liver. The mRNA levels were measured by quantitative PCR and the antioxidant capacity was detected using H2O2-specific fluorescent probe. Here, polydatin strongly alleviated hepatic steatosis and decreased the expression levels of alcohol and lipid metabolism-related genes, including CYP2Y3, CYP3A65, HMGCRa, HMGCRb and FASN. Additionally, polydatin inhibited oxidative stress in the liver according to fluorescent probe. Moreover, significantly up-regulated expression of DNA damage-related genes (CHOP, GADD45αa) revealed that polydatin attenuated hepatic apoptosis in larvae. In conclusion, polydatin may improve the liver function of zebrafish with acute alcoholic liver injury through attenuating hepatic fat accumulation, ameliorating lipid and ethanol metabolism and reducing oxidative stress and DNA damage.
•Previous studies included the tongue, mouth floor, buccal mucosa sites, etc.•The mircobial correlation between GSCC and periodontitis has not been illustrated.•10 GSCC patients, 15 periodontitis ...patients, and 15 healthy individuals were recruited.•Subgingival plaque, saliva, swabs, etc. were collected for 16S rDNA sequencing.•A high level of Atopobium and LPS biosynthesis potentially increase the risk of GSCC.
Previous studies have proved that periodontitis is an independent risk factor of oral squamous cell carcinoma (OSCC) epidemiologically. Along with the important role of microbiota in the cancer process and the specific anatomical position, our study explored the microbial composition and functions in periodontitis and gingival squamous cell carcinoma (GSCC).
GSCC patients (n = 10), matched periodontitis patients (n = 15), and healthy individuals (n = 15) were recruited. Saliva, subgingival plaque, tongue dorsum, buccal mucosa, cancerous tissue, and paracancerous tissue samples were collected. 16S rDNA amplicon sequencing and functional prediction were applied for the taxonomic analysis.
Periodontal pathogens occupied 46% in GSCC. Besides, the mutual operational taxonomy unites (OTU) generated from the subgingival plaque occupied 38.36% and 44.13% from saliva. Fusobacterium, Peptostreptococcus, and Prevotella were more abundant in cancerous tissues, while Streptococcus, Neisseria, and Haemophilus were more enriched in saliva or soft mucosa. PCoA exhibited similar cluster between tongue dorsum and saliva in GSCC. GSCC showed lower richness than periodontitis. In saliva and subgingival plaque, Atopobium was more prevalent in GSCC than periodontitis and controls in descending order. Lipopolysaccharide (LPS) biosynthesis increased in subgingival plaque of GSCC compared with the other two groups.
Periodontal pathogens were abundant in GSCC. Cancerous tissues harbor enriched periodontal pathogens while saliva or soft mucosa harbored more periodontal health related bacteria. A high level of Atopobium in saliva and LPS biosynthesis have the potential for increasing the risk of suffering from GSCC in individuals with periodontitis, which needs more evidence to clarify it.
Mitophagy is a metabolic process to remove excessive or damaged mitochondria in eukaryotic cells. It is well-known that mitochondria are one of the major sources of reactive oxygen species (ROS). ...Mitochondrial ROS and damage-associated molecular patterns (DAMPs) can activate inflammasomes to induce inflammatory responses. Once the activation is regulated improperly, excessive inflammation will bring about various tissue injuries, resulting in a series of diseases. However, the selective mitochondrial autophagy can specifically eliminate dysfunctional mitochondria to maintain mitochondrial homeostasis and protect against the hyperinflammation induced by ROS and DAMPs. Recent studies demonstrated that a variety of internal and external factors regulate several inflammatory diseases
via
altering the level of mitophagy. In this review, we summarize the latest research progress of mitophagy and focus on the inflammatory responses regulated by mitophagy, aiming to illuminate the role of mitophagy in inflammation and provide clues to the diagnosis and therapy of inflammatory diseases.
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•Cruciform biaxial tensile test were performed in rolling/transverse and 45°/135° sampling directions under different loading paths.•Priority of calibrating the material parameters ...with the equi-biaxial data should be ensured.•The introduction of plane strain yield stresses are positive for the accurate prediction of plastic anisotropy.•Non-integer exponent is helpful to improve the description accuracy of anisotropy yield behavior.•Biaxial tensile data under principal stress state are not enough to evaluate the best identification method.
It is necessary to identify differences among biaxial tensile mechanical properties to describe the plastic anisotropy and potential adjustment ability of yield criteria with the non-integer exponent for the yield surface. Therefore, in this study, uniaxial and cruciform biaxial tensile tests were performed under 17 different loading paths: uniaxial tension in seven different directions, cruciform biaxial tension in rolling/transverse and 45°/135° sampling directions with seven and three different stress ratios, respectively. Based on the BBC2008 yield criterion, the uniaxial yield stresses, rθ-values, yield loci on the normal plane, and shear yield loci on the diagonal plane, predicted using six parameter identification strategies, were quantitatively evaluated for MP980, DP490, 6016-T4, and 5182-O. Results show the constraining and regulation ability of the equi-biaxial tensile data for yield loci to be better than that of near-plane strain state data. The parameter identification strategy considering the non-integer exponent was observed to significantly improved the ability of the yield criterion to describe the anisotropic yield behavior. For a simplified evaluation system that considers only the prediction accuracy of the yield locus under the principal stress state, neglecting the prediction accuracy for the shear yield locus may lead to incorrect judgments regarding the best identification strategy.
Primary cilia are microtubule-based solitary membrane projections on the cell surface that play important roles in signaling and development. Recent studies have demonstrated that polarized vesicular ...trafficking involving the small GTPase Rab8 and its guanine nucleotide exchange factor Rabin8 is essential for primary ciliogenesis. In this study, we show that a highly conserved region of Rabin8 is pivotal for its activation as a guanine nucleotide exchange factor for Rab8. In addition, in its activated conformation, Rabin8 interacts with Sec15, a subunit of the exocyst and downstream effector of Rab8. Expression of constitutively activated Rab8 promotes the association of Sec15 with Rabin8. Using immunofluorescence microscopy, we found that Sec15 co-localized with Rab8 along the primary cilium. Inhibition of Sec15 function in cells led to defects in primary ciliogenesis. The Rabin8-Rab8-Sec15 interaction may couple the activation of Rab8 to the recruitment of the Rab8 effector and is involved in the regulation of vesicular trafficking for primary cilium formation.
Background: Exocytosis at the plasma membrane mediated by Rabin8 is essential for primary ciliogenesis.
Results: Rabin8 activation involves the relief of its autoinhibition. Rabin8 interacts with the exocyst component Sec15 upon its activation.
Conclusion: The Rab8 guanine nucleotide exchange factor-effector interaction is important for exocytosis and primary ciliogenesis.
Significance: The study sheds light on our understanding of the regulation of exocytosis and ciliogenesis.
A significant proportion of oropharyngeal squamous cell carcinomas (OSCC) are associated with the human papilloma virus (HPV), particularly HPV16. The optimal method for HPV determination on archival ...materials however, remains unclear. We compared a quantitative real-time polymerase chain reaction (qRT-PCR) assay for HPV16 mRNA to a DNA in situ hybridization (ISH) method, and evaluated their significance for overall (OS) and disease-free (DFS) survival.
Matched, archival biopsies from 111 patients with OSCC were evaluated for HPV16 using a qRT-PCR for E6 mRNA and ISH for DNA. Immunohistochemistry for p16, p53, and epidermal growth factor receptor were also performed.
HPV16 E6 mRNA was positive in 73 (66%) of 111 samples; ISH was positive in 62 of 106 samples (58%), with 86% concordance. P16 was overexpressed in 72 samples (65%), which was strongly associated with HPV16 status by either method. E6 mRNA presence or p16 overexpression were significantly associated with superior OS; E6 mRNA, HPV16 ISH, or p16 were all significantly associated with DFS. On multivariate analysis adjusted for age, stage, and treatment, positive E6 mRNA was the only independent predictor for superior OS; for DFS, p16 expression or HPV16 status determined by either method was significant.
The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two assays are technically easier to perform; hence, HPV16 ISH or p16 IHC should become standard evaluations for all patients with OSCC.
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