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Dynamic alteration of the epitranscriptome exerts regulatory effects on the lifecycle of oncogenic viruses in vitro. However, little is known about these effects in vivo because of the general lack of suitable animal infection models of these viruses. Using a model of rapid-onset Marek's disease lymphoma in chickens, we investigated changes in viral and host messenger RNA (mRNA) N6-methyladenosine (m

Background Lung adenocarcinoma (LUAD), as the most common subtype of lung cancer, is the leading cause of cancer deaths in the world. The accumulation of driver gene mutations enables cancer cells to gradually acquire growth advantage. Therefore, it is important to understand the functions and interactions of driver gene mutations in cancer progression. Methods We obtained gene mutation data and gene expression profile of 506 LUAD tumors from The Cancer Genome Atlas (TCGA). The subtypes of tumors with driver gene mutations were identified by consensus cluster analysis. Results We found 21 significantly mutually exclusive pairs consisting of 20 genes among 506 LUAD patients. Because of the increased transcriptomic heterogeneity of mutations, we identified subtypes among tumors with non‐silent mutations in driver genes. There were 494 mutually exclusive pairs found among driver gene mutations within different subtypes. Furthermore, we identified functions of mutually exclusive pairs based on the hypothesis of functional redundancy of mutual exclusivity. These mutually exclusive pairs were significantly enriched in nuclear division and humoral immune response, which played crucial roles in cancer initiation and progression. We also found 79 mutually exclusive triples among subtypes of tumors with driver gene mutations, which were key roles in cell motility and cellular chemical homeostasis. In addition, two mutually exclusive triples and one mutually exclusive triple were associated with the overall survival and disease‐specific survival of LUAD patients, respectively. Conclusions We revealed novel mutual exclusivity and generated a comprehensive functional landscape of driver gene mutations, which could offer a new perspective to understand the mechanisms of cancer development and identify potential biomarkers for LUAD therapy., We revealed novel mutual exclusivity and generated a comprehensive functional landscape of driver gene mutations, which could offer a new perspective to understand the mechanisms of cancer development and identify biomarkers for LUAD therapy.

The evolutionary dynamics of human cancers has been investigated popularly and several bifurcated paths in cancer evolutionary trajectories are revealed to be with differential outcomes and phenotypes. However, whether such bifurcated paths exist in glioblastoma (GBM) remains unclear. In 385 GBM samples, through determining the clonal status of cancer driver events and inferring their temporal order, we constructed a temporal map of evolutionary trajectories at the patient population level. By investigating the differential impact on clinical outcome, we identified four key bifurcated paths, namely, "chromosome 10 copy number loss (ie, 10 loss) → chromosome 19 copy number gain (ie, 19 gain): 10 loss → 13q loss"; "10 loss → 19 gain: 10 loss → 15q loss"; "10 loss → 19 gain: 10 loss → 6q loss" and "10 loss → 19 gain: 10 loss → 16q loss". They formed a core multibranches path, with 10 loss being regarded as the common earliest event followed by 19 gain and four other departure events (13q loss, 15q loss, 6q loss and 16q loss), which may account for their difference in genome instability and patient survival time. Compared to "10 loss → 19 gain", the patients with "10 loss → 13q loss" had higher telomerase activity. Notably, there were obvious discrepancies in immune activity and immune cell infiltration level between patients with "10 loss → 13q/16q loss" and "10 loss → 19 gain", highlighting the bifurcated paths' effect on tumor immune microenvironment. In summary, our study identifies four key bifurcated paths in GBM for the first time, suggesting the feasibility of patient stratification and prognosis prediction based on key bifurcated paths.

The shuttle effect caused by soluble lithium polysulfides (LiPSs) and intrinsic slow electrochemical transformation from LiPSs to Li2 S/Li2 S2 will induce undesirable cycling performance, which is the primary obstruct limiting the practical applications of lithium-sulfur (Li-S) batteries. Here a convenient method is designed to fabricate the 2D louts-like N-Co2 VO4 -Co heterostructures with well-abundant interfaces and oxygen vacancies (Vo ), endowing the materials with both "sulfiphilic" and "lithiophilic" features. When employed as the modification layer coated on commercial Celgard 2400 separator, the as-prepared N-Co2 VO4 -Co/PP with synergistic adsorption-electrocatalysis effects achieves desirable sulfur electrochemistry, thus showing a high initial discharge capacity of 1466.4 mAh g-1 at 0.1 C and stable cycle life with a fade rate of 0.03% per cycle over 1000 cycle at 3.0 C. Moreover, a superior areal capacity of 12.84 mAh cm-2 is preserved under high sulfur loading of 14.3 mg cm-2 .

Vascular calcification (VC) is a major contributor of cardiovascular dysfunction in chronic renal failure (CRF). Citrate binds calcium and inhibits the growth of calcium crystals. This present study intends to evaluate the effect of citrate on VC in adenine-induced CRF rats. The rats were randomly divided into five groups: the control group, the citrate control group, model group, model rats with low-dose treatment of citrate (216 mg/kg) and model rats with high-dose treatment of citrate (746 mg/kg). The rats were euthanized at 5 weeks with their blood and aorta in detection. The results showed that serum level of blood urea nitrogen, serum creatinine, phosphorus, calcium, and related renal failure function marker were elevated in the model group. Furthermore, the aortic calcium accumulation and alkaline phosphatase activity were significantly increased in the model group compared with control groups. Additionally, hematoxylin-eosin staining results demonstrated that the vascular calcification in aorta is significantly increased in the model group. Finally, the expression of VC-related proteins including bone morphogenetic protein and osteocalcin were increased in the model group, whereas alpha-smooth muscle actin was decreased in the model group compared with the control group. However, treatment with citrate caused a reversal effect of all the above events in a dose-dependent manner. In conclusion, citrate may attenuate vascular calcification in adenine-induced CRF rats.

Background and Aims Hepatic fibrosis represents a major cause of morbidity and mortality worldwide. The present study was to evaluate the antifibrogenesis effect of paeonol and involved mechanisms. Methods The degree of liver injury was evaluated biochemically by measuring serum and fibrotic markers and pathological examination. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and trypan blue staining. Cytotoxic effects were determined using lactate dehydrogenase release assay. Cell cycle was determined using single dyeing methods of propidium iodide (PI) by flow cytometry. Apoptosis was confirmed using double-staining of annexin V/PI and Hoechst. Western blot, immunofluorescence and real-time polymerase chain reaction were used to explore the molecular mechanisms. Results Treatment with paeonol significantly protected the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, improving the histological architecture of the liver, and by inhibiting activation of hepatic stellate cells (HSCs) in vivo. Interestingly, paeonol had no apparent cytotoxic effects but could markedly inhibit primary HSC proliferation and induced HSC cell cycle arrest at the G2/M checkpoint. These effects were caused by paeonol suppression of phosphorylation of cycle protein cdc2 and of CDK2. Moreover, that paeonol triggered mitochondrial apoptosis pathway and led to activation of caspase cascades in HSCs was found. Mechanistic investigations revealed that the nuclear factor-κB (NF-κB) pathway inhibition resulted in the earlier events. Furthermore, paeonol altered the expression of some marker proteins relevant to HSCs activation. Conclusion Paeonol could inhibit HSC proliferation and induce mitochondrial apoptosis via disrupting NF-κB pathway, which might be the mechanisms of paeonol reduction of liver fibrosis.

Sintering of pure B4C and Ni2B nanolayer-coated B4C was studied from 1300° to 1600°C, with the holding time at the peak temperatures being 2 or 10 h. Compacts were made by uniaxial die compaction and combustion-driven compaction. Pure B4C sample shows less sintering at all conditions. Ni2B-coated B4C sample shows more extensive densification, neck formation, and grain shape accommodation. The combustion driven compaction process accelerates sintering by offering higher green density to start with. The Ni2B species on the B4C particle surfaces melts into a nickel–boron-containing liquid phase during heating, remains as liquid during sintering, and then transforms into Ni4B3 and NiB during cooling. High-resolution composition analysis shows that there is no nickel diffusion into bulk B4C during the sintering process. However, there is boron diffusion into the Ni2B coating layer. Carbon diffusion cannot be directly measured but is believed to be a simultaneous process as boron diffusion. A multievent sintering process has been proposed to explain the observations.

Nanoparticle material forming is challenging because of loose packing and agglomeration issues intrinsic to nanoparticles. Liquid processing shows great potential to overcome such hurdles. This study is focused on nanoparticle colloidal processing and freeze-casting forming. Al2O3 nanoparticle suspensions are examined, and microstructure evolution of Al2O3 nanoparticle suspension during freeze casting is discussed. The “Fines” effect influences nanoparticle packing on freeze-cast sample surfaces. Trapped air bubbles in the suspension lead to a porous bulk microstructure. Prerest is necessary for dense and homogeneous green microstructure formation. The green strength, fracture mode, and ability to form fine features by freeze casting are also evaluated.