This study aimed to identify differential circular RNA (circRNA) in the plasma exosomes of patients with lung adenocarcinoma (LUAD) using high‐throughput sequencing. First, exosomes were isolated ...using an exosome isolation kit and confirmed by Western blotting, transmission electron microscopy, and NanoSight Assay. Subsequently, plasma circRNA expression profiles were screened by high‐throughput sequencing and confirmed by fluorescence quantitative real‐time polymerase chain reaction (qRT‐PCR) and Sanger sequencing. Finally, the circRNA‐miRNA‐mRNA network was performed to forecast the potential function of circRNAs. The result of high‐throughput sequencing data documented that 182 differentially expressed exosomal circRNAs in all were screened, which included 105 that were upregulated and 78 that were downregulated in LUAD patients plasma compared with controls. The four upregulated circRNAs including circ_0001492, circ_0001346, circ_0000690, and circ_0001439 were identical to the sequencing data by qRT‐PCR, and their latent circRNA‐miRNA‐mRNA interactions were exhibited. Taken together, our study firstly revealed the altered exosomal circRNA expression from plasma samples in patients with LUAD and supports the need for exploring their potential as biomarkers and the pathological effects of lung cancer.
1.
The comprehensive expression profiles of circular RNAs (circRNAs) in plasma exosomes of early‐stage lung adenocarcinoma (LUAD) are firstly illustrated.
2.
Four exosomal circRNAs are definitely dysregulated based on quantitative real‐time polymerase chain reaction.
3.
Potential microRNA and targets gene are predicted for these validated circRNAs.
4.
CircRNAs of exosomes may act as novel noninvasive biomarkers for LUAD.
Product reviews play an important role in guiding users’ purchase decision-making in e-commerce platforms. However, it is challenging for users to find helpful reviews that meet their preferences and ...experiences among an overwhelming amount of reviews. Some works have been done to recommend helpful reviews to users, either from personalized or non-personalized views. While some existing models recommend similar users’ reviews for a target user, they either neglect the target user’s aspect preferences or the user-product interactions for measuring user similarity. Moreover, those models predict review helpfulness at the review-level (a review is taken as a whole); few of them consider the aspect-level. To address the above issues, we propose an aspect sentiment similarity-based personalized review recommendation model (
A2SPR
), which quantifies review helpfulness and recommends reviews that are customized for each individual. We analyze users’ aspect preferences from reviews and improve user similarity with users’ fine-grained sentiment and product relevance. Furthermore, we redefine the review helpfulness score at the aspect level, which indicates the review’s reference value for users’ purchase decisions. Finally, we recommend the top
k
helpful reviews for individuals based on the review helpfulness score. To validate the performance of the proposed model, eight baselines are developed and compared. Experimental results show that our model performs better than those baselines in both the coverage and precision.
Various behaviours of nonlinear wave propagation and competition have been discussed and investigated extensively and meticulously, especially when the media are homogeneous. However, corresponding ...studies in heterogeneous media are much scarcer. In this paper, spontaneously generated waves from one-dimensional heterogeneous oscillatory media, modelled by complex Ginzburg-Landau equations with spatially varied controlling parameters, are investigated. An unexpected homogeneous wave train clearly emerges under certain conditions. With the theory of interface-selected waves, we can theoretically predict the frequencies and wavenumbers under several conditions. This kind of wave train can be found in a wide region of parameter space. These phenomena are robust when parameters are varied nonlinearly or linearly with fluctuation. Moreover, this kind of homogeneous wave plays an important role in wave competition and affects wave propagation in spatially heterogeneous nonlinear systems, which will bring new applications of heterogeneity and provide new ideas for wave control.
The fatty liver hemorrhage syndrome in laying hens is a disease of lipid metabolism disorders. Importantly, energy sensor AMP-activated protein kinase (AMPK) plays an essential role in homeostasis ...regulation of liver lipid. The current research aims to investigate the relationship between AMPK signaling pathway and lipid metabolism in laying hen hepatocytes and explore the underlying mechanisms. The steatotic hepatocytes model of laying hen was established and treated with AMPK agonist AICAR and inhibitor compound C. The results showed that the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly declined while high-density lipoprotein cholesterol level increased in the AICAR-treated steatosis group compared with the steatosis group. Furthermore, the mRNA levels of liver kinase B1 and AMP-activated protein kinase α1 declined significantly in the steatosis group compared with those in the normal group. However, AMPK activation significantly upregulated the mRNA levels of peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase-1 while downregulated the mRNA levels of acetyl CoA carboxylase, fatty acid synthase, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, Sn-glycerol-3-phosphate acyltransferase, and hepatocyte nuclear factor 4α. These results suggest that activated AMPK signaling pathway increases fatty acid oxidation and reduces lipid synthesis in laying hen hepatocytes, thereby ameliorating liver steatosis.
Type 2 (T2)-low asthma can be severe and corticosteroid-resistant. Airway epithelial cells play a pivotal role in the development of asthma, and mitochondria dysfunction is involved in the ...pathogenesis of asthma. However, the role of epithelial mitochondria dysfunction in T2-low asthma remains unknown.
Differentially expressed genes (DEGs) were identified using gene expression omnibus (GEO) dataset GSE4302, which is originated from airway epithelial brushings from T2-high (n = 22) and T2-low asthma patients (n = 20). Gene set enrichment analysis (GSEA) was implemented to analyze the potential biological pathway involved between T2-low and T2-high asthma. T2-low asthma related genes were identified using weighted gene co-expression network analysis (WGCNA). The mitochondria-related genes (Mito-RGs) were referred to the Molecular Signatures Database (MSigDB). T2-low asthma related mitochondria (T2-low-Mito) DEGs were obtained by intersecting the DEGs, T2-low asthma related genes, and Mito-RGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to further explore the potential function of the T2-low-Mito DEGs. In addition, the hub genes were further identified by protein-protein interaction (PPI), and the expressions of hub genes were verified in another GEO dataset GSE67472 and bronchial brushings from patients recruited at Tongji Hospital.
Six hundred and ninety-two DEGs, including 107 downregulated genes and 585 upregulated genes were identified in airway epithelial brushings from T2-high and T2-low asthma patients included in GSE4302 dataset. GSEA showed that mitochondrial ATP synthesis coupled electron transport is involved in T2-low asthma. Nine hundred and four T2-low asthma related genes were identified using WGCNA. Twenty-two T2-low-Mito DEGs were obtained by intersecting the DEGs, T2-low asthma and Mito-RGs. The GO enrichment analysis of the T2-low-Mito DEGs showed significant enrichment of mitochondrial respiratory chain complex assembly, and respiratory electron transport chain. PPI network was constructed using 22 T2-low-Mito DEGs, and five hub genes,
,
,
,
, and
, were identified. Moreover, the expression of these hub genes was validated in another GEO dataset, and our cohort of asthma patients.
This study suggests that mitochondria dysfunction contributes to T2-low asthma.
BackgroundMinor (i.e., <20% prevalence) drug-resistant human immunodeficiency virus (HIV) variants may go undetected, yet be clinically important ObjectivesTo compare the prevalence of drug-resistant ...variants detected with standard and ultra-deep sequencing (detection down to 1% prevalence) and to determine the impact of minor resistant variants on virologic failure (VF) MethodsThe Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study (N = 1397) compared 3 initial antiretroviral therapy (ART) strategies. A random subset (n = 491) had baseline testing for drug-resistance mutations performed by use of standard sequencing methods. Ultra-deep sequencing was performed on samples that had sufficient viral content (N = 264). Proportional hazards models were used to compare rates of VF for those who did and did not have mutations identified ResultsMutations were detected by standard and ultra-deep sequencing (in 14% and 28% of participants, respectively; P<.001). Among individuals who initiated treatment with an ART regimen that combined nucleoside and nonnucleoside reverse-transcriptase inhibitors (hereafter, “NNRTI strategy”), all individuals who had an NNRTI-resistance mutation identified by ultra-deep sequencing experienced VF. When these individuals were compared with individuals who initiated treatment with the NNRTI strategy but who had no NNRTI-resistance mutations, the risk of VF was higher for those who had an NNRTI-resistance mutation detected by both methods (hazard ratio HR, 12.40 95% confidence interval {CI}, 3.41–45.10) and those who had mutation(s) detected only with ultra-deep sequencing (HR, 2.50 95% CI, 1.17–5.36) ConclusionsUltra-deep sequencing identified a significantly larger proportion of HIV-infected, treatment-naive persons as harboring drug-resistant viral variants. Among participants who initiated treatment with the NNRTI strategy, the risk of VF was significantly greater for participants who had low- and high-prevalence NNRTI-resistant variants
4-1BB (CD137, TNFRSF9) is a costimulatory receptor expressed on several subsets of activated immune cells. Numerous studies of mouse and human T cells indicate that 4-1BB promotes cellular ...proliferation, survival, and cytokine production. 4-1BB agonist mAbs have demonstrated efficacy in prophylactic and therapeutic settings in both monotherapy and combination therapy tumor models and have established durable anti-tumor protective T-cell memory responses. PF-05082566 is a fully human IgG2 that binds to the extracellular domain of human 4-1BB with high affinity and specificity. In preclinical studies, this agonist antibody demonstrated its ability to activate NF-κB and induce downstream cytokine production, promote leukocyte proliferation, and inhibit tumor growth in a human PBMC xenograft tumor model. The mechanism of action and robust anti-tumor efficacy of PF-05082566 support its clinical development for the treatment of a broad spectrum of human malignancies.
Adverse reactions reported in patients treated with antibody-calicheamicin conjugates such as gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin include thrombocytopenia and sinusoidal ...obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury, and identify potential safety biomarkers.
Cynomolgus monkeys were dosed intravenously at 6 mg/m
/dose once every 3 weeks with a nonbinding antibody-calicheamicin conjugate (PF-0259) containing the same linker-payload as gemtuzumab ozogamicin and inotuzumab ozogamicin. Monkeys were necropsied 48 hours after the first administration (day 3) or 3 weeks after the third administration (day 63).
PF-0259 induced acute thrombocytopenia (up to 86% platelet reduction) with nadirs on days 3 to 4. There was no indication of effects on megakaryocytes in bone marrow or activation of platelets in peripheral blood. Microscopic evaluation of liver from animals necropsied on day 3 demonstrated midzonal degeneration and loss of sinusoidal endothelial cells (SECs) associated with marked platelet accumulation in sinusoids. Liver histopathology on day 63 showed variable endothelial recovery and progression to a combination of sinusoidal capillarization and sinusoidal dilation/hepatocellular atrophy, consistent with early SOS. Among biomarkers evaluated, there were early and sustained increases in serum hyaluronic acid (HA) that correlated well with serum aspartate aminotransferase and liver microscopic changes, suggesting that HA may be a sensitive diagnostic marker of the liver microvascular injury.
These data support the conclusion that target-independent damage to liver SECs may be responsible for acute thrombocytopenia (through platelet sequestration in liver sinusoids) and development of SOS.
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At high magnetic fields, monolayer graphene hosts competing phases distinguished by their breaking of the approximate SU(4) isospin symmetry. Recent experiments have observed an even denominator ...fractional quantum Hall state thought to be associated with a transition in the underlying isospin order from a spin-singlet charge density wave at low magnetic fields to an antiferromagnet at high magnetic fields, implying that a similar transition must occur at charge neutrality. However, this transition does not generate contrast in typical electrical transport or thermodynamic measurements and no direct evidence for it has been reported, despite theoretical interest arising from its potentially unconventional nature. Here, we measure the transmission of ferromagnetic magnons through the two-dimensional bulk of clean monolayer graphene. Using spin polarized fractional quantum Hall states as a benchmark, we find that magnon transmission is controlled by the detailed properties of the low-momentum spin waves in the intervening Hall fluid, which is highly density dependent. Remarkably, as the system is driven into the antiferromagnetic regime, robust magnon transmission is restored across a wide range of filling factors consistent with Pauli blocking of fractional quantum Hall spin-wave excitations and their replacement by conventional ferromagnetic magnons confined to the minority graphene sublattice. Finally, using devices in which spin waves are launched directly into the insulating charge-neutral bulk, we directly detect the hidden phase transition between bulk insulating charge density wave and a canted antiferromagnetic phase at charge neutrality, completing the experimental map of broken-symmetry phases in monolayer graphene.
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