Insight into Interfacial Heat Transfer of ß-Ga2O3/Diamond Heterostructures via the Machine Learning Potential.

ß-Ga2O3 is an ultrawide-band gap semiconductor with excellent potential for high-power and ultraviolet optoelectronic device applications. Low thermal conductivity is one of the major obstacles to enable the full performance of ß-Ga2O3-based devices. A promising solution for this problem is to integrate ß-Ga2O3 with a diamond heat sink. However, the thermal properties of the ß-Ga2O3/diamond heterostructures after the interfacial bonding have not been studied extensively, which are influenced by the crystal orientations and interfacial atoms for the ß-Ga2O3 and diamond interfaces. In this work, molecular dynamics simulations based on machine learning potential have been adopted to investigate the crystal-orientation-dependent and interfacial-atom-dependent thermal boundary resistance (TBR) of the ß-Ga2O3/diamond heterostructure after interfacial bonding. The differences in TBR at different interfaces are explained in detail through the explorations of thermal conductivity value, thermal conductivity spectra, vibration density of states, and interfacial structures. Based on the above explorations, a further understanding of the influence of different crystal orientations and interfacial atoms on the ß-Ga2O3/diamond heterostructure was achieved. Finally, insightful optimization strategies have been proposed in the study, which could pave the way for better thermal design and management of ß-Ga2O3/diamond heterostructures according to guidance in the selection of the crystal orientations and interfacial atoms of the ß-Ga2O3 and diamond interfaces.

Interfacial Optimization for AlN/Diamond Heterostructures via Machine Learning Potential Molecular Dynamics Investigation of the Mechanical Properties.

AlN/diamond heterostructures hold tremendous promise for the development of next-generation high-power electronic devices due to their ultrawide band gaps and other exceptional properties. However, the poor adhesion at the AlN/diamond interface is a significant challenge that will lead to film delamination and device performance degradation. In this study, the uniaxial tensile failure of the AlN/diamond heterogeneous interfaces was investigated by molecular dynamics simulations based on a neuroevolutionary machine learning potential (NEP) model. The interatomic interactions can be successfully described by trained NEP, the reliability of which has been demonstrated by the prediction of the cleavage planes of AlN and diamond. It can be revealed that the annealing treatment can reduce the total potential energy by enhancing the binding of the C and N atoms at interfaces. The strain engineering of AlN also has an important impact on the mechanical properties of the interface. Furthermore, the influence of the surface roughness and interfacial nanostructures on the AlN/diamond heterostructures has been considered. It can be indicated that the combination of surface roughness reduction, AlN strain engineering, and annealing treatment can effectively result in superior and more stable interfacial mechanical properties, which can provide a promising solution to the optimization of mechanical properties, of ultrawide band gap semiconductor heterostructures.

New Insight into the Function of Dopamine (DA) during Cd Stress in Duckweed (Lemna turionifera 5511).

Dopamine (DA), a kind of neurotransmitter in animals, has been proven to cause a positive influence on plants during abiotic stress. In the present study, the function of DA on plants under cadmium (Cd) stress was revealed. The yellowing of duckweed leaves under Cd stress could be alleviated by an exogenous DA (10/20/50/100/200 µM) supplement, and 50 µM was the optimal concentration to resist Cd stress by reducing root breakage, restoring photosynthesis and chlorophyll content. In addition, 24 h DA treatment increased Cd content by 1.3 times in duckweed under Cd stress through promoting the influx of Cd2+. Furthermore, the gene expression changes study showed that photosynthesis-related genes were up-regulated by DA addition under Cd stress. Additionally, the mechanisms of DA-induced Cd detoxification and accumulation were also investigated; some critical genes, such as vacuolar iron transporter 1 (VIT1), multidrug resistance-associated protein (MRP) and Rubisco, were significantly up-regulated with DA addition under Cd stress. An increase in intracellular Ca2+ content and a decrease in Ca2+ efflux induced by DA under Cd stress were observed, as well as synchrony with changes in the expression of cyclic nucleotide-gated ion channel 2 (CNGC2), predicting that, in plants, CNGC2 may be an upstream target for DA action and trigger the change of intracellular Ca2+ signal. Our results demonstrate that DA supplementation can improve Cd resistance by enhancing duckweed photosynthesis, changing intracellular Ca2+ signaling, and enhancing Cd detoxification and accumulation. Interestingly, we found that exposure to Cd reduced endogenous DA content, which is the result of a blocked shikimate acid pathway and decreased expression of the tyrosine aminotransferase (TAT) gene. The function of DA in Cd stress offers a new insight into the application and study of DA to Cd phytoremediation in aquatic systems.

Mechanism of calcium signal response to cadmium stress in duckweed.

Cadmium (Cd) causes serious damage to plants. Although calcium (Ca) signal has been found to respond to certain stress, the localization of Ca and molecular mechanisms underlying Ca signal in plants during Cd stress are largely unknown. In this study, Ca2+-sensing fluorescent reporter (GCaMP3) transgenic duckweed showed the Ca2+ signal response in Lemna turionifera 5511 (duckweed) during Cd stress. Subsequently, the subcellular localization of Ca2+ has been studied during Cd stress by transmission electron microscopy, showing the accumulation of Ca2+ in vacuoles. Also, Ca2+ flow during Cd stress has been measured. At the same time, the effects of exogenous glutamic acid (Glu) and γ-aminobutyric (GABA) on duckweed can better clarify the signal operation mechanism of plants to Cd stress. The molecular mechanism of Ca2+ signal responsed during Cd stress showed that Cd treatment promotes the positive response of Ca signaling channels in plant cells, and thus affects the intracellular Ca content. These novel signal studies provided an important Ca2+ signal molecular mechanism during Cd stress.

Serum-derived exosomes induce proinflammatory cytokines production in Cynoglossus semilaevis via miR-133-3p.

Exosomes are small membrane-enclosed vesicles secreted by various types of cells. In mammals, a wide range of physiological and pathological functions have been confirmed and attributed to EVs carrying a variety of molecular cargoes, including miRNAs. However, studies on the biological functions and related molecular mechanisms of serum exosomes isolated from teleost fish are limited. Indeed, the molecular mechanisms underlying the effects of serum exosomes on immune responses and inflammatory processes are unknown. Chinese tongue sole (Cynoglossus semilaevis) is an economically important species used widely in industrial aquaculture. Vibrio harveyi, a common bacterial pathogen that infects C. semilaevis and some other fish, causes excessive inflammatory reactions, which are characterized by skin ulceration. Here, we isolated serum-derived exosomes from C. semilaevis and investigated their effects on inflammatory processes following V. harveyi infection. We found that compared with uninfected fish, exosome abundance in infected fish blood increased with bacterial infection time, while expression of TNF-α increased, and that of IL-10 decreased, significantly. Moreover, artificial infection studies demonstrated that injection of serum exosomes isolated from infected fish increased expression of TNF-α, IL-6, and IL-8, which is consistent with the increase in proinflammatory cytokines induced by V. harveyi infection. To further investigate the mechanisms by which exosomes increase proinflammatory cytokine production, we performed miRNA expression profiling and found that 26 differentially expressed miRNAs were associated with bacterial infection and immune responses; of these, miR-133-3p was considerably more abundant in serum exosomes from infected fish. Bioinformatics analysis suggested that miR-133-3p inhibits NF-κB signaling pathways by targeting PP2A and affecting cytokine release. We also found that miR-133-3p increased expression of TNF-α, IL-6, and IL-8 in fish blood and kidney, whereas an miR-133-3p inhibitor showed the opposite results. Thus, the data suggest that serum exosomes participate in innate immunity in teleost fish by promoting inflammatory responses to bacterial infection. Exosome-mediated transfer of miR-133-3p increases expression of proinflammatory cytokines in C. semilaevis, resulting in excessive inflammatory responses during V. harveyi infection. These data may lead to development of methods and strategies that control skin ulceration in Chinese tongue sole.

The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia.

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (Vmem) and quiescence. We found that Vmem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas Vmem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high Vmem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and Vmem in the Artemia model.

MicroRNA expression profiling in exosomes derived from gastric cancer stem-like cells.

Cancer stem-like cells (CSCs) have been identified as the initial cell in formation of cancer. Quiescent CSCs can "hide out" from traditional cancer therapy which may produce an initial response but are often unsuccessful in curing patients. Thus, levels of CSC in patients may be used as an indicator to measure the chance of recurrence of cancer after therapy. The goals of our work are to develop specific exosomal miRNA clusters for gastric CSCs that can potentially predict which patients are at high risk for developing gastric cancer (GC) in order to diagnose GC at an early stage. Here, upon sorting gastric CSCs, we initially isolated and characterized exosomes secreted by both gastric CSCs and their differentiated cells (DCs). By deep sequencing of each exosomal miRNA library, 11 typical differentially expressed miRNAs were identified as signature miRNAs for CSC. Gene target prediction, GO annotation and KEGG pathway enrichment analysis showed possible functions associated with these signature miRNAs. Hence, upon research of exosomal miRNAs that would influence behavior of tumor cells and their microenvironment, this study shows that a specific miRNA signature is present in CSCs, and implies that a potential miRNA biomarker reflecting the stage of gastric cancer progression and metastasis could be developed in the foreseeable future.

Identification of exosomes and its signature miRNAs of male and female Cynoglossus semilaevis.

Exosomes are small membrane particles which are widely found in various cell lines and physiological fluids in mammalian. MicroRNAs (miRNAs) enclosed in exosomes have been identified as proper signatures for many diseases and response to therapies. However, the composition of exosomes and enclosed miRNAs in fishes has not been investigated. Cynoglossus semilaevis is an important commercial flatfish with ambiguous distinction between males and females before sex maturation, which leads to screening difficulty in reproduction and cultivation. An effective detection method was required for sex differentiation of C. semilaevis. In this work, we successfully identified exosomes in C. semilaevis serum. The analysis of nucleotide composition showed that miRNA dominated in exosomes. Thereafter the miRNA profiles in exosomes from males and females were sequenced and compared to identify the signature miRNAs corresponding to sex differentiation. The functions of signature miRNAs were analyzed by target matching and annotation. Furthermore, 7 miRNAs with high expression in males were selected from signature miRNAs as the markers for sex identification with their expression profiles verified by real time quantitative PCR. Exosomes were first found in fish serum in this work. Investigation of marker miRNAs supplies an effective index for the filtration of male and female C. semilaevis in cultivation.

UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians.

PURPOSE: Previous studies confirmed that genotyping uridine diphosphate glucuronosyltransferase (UGT) 1A1*28 polymorphisms could predict the side effects in cancer patients using irinotecan (IRI) and then reduce IRI-induced toxicity by preventative treatment or decrease in dose. However, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in Asian patients is still unclear. The aim of this study was to evaluate the association between UGT1A1*6 polymorphisms and IRI-induced severe neutropenia as well as diarrhea in Asian patients. METHODS: We searched all papers on PubMed and Embase from February 1998 to August 2013. Then we assessed the methodologies quality, extracted data and made statistics analysis using STATA software. To uncover the sources of heterogeneity, subgroup meta-analysis was conducted according to the dosage of IRI. RESULTS: Eleven papers were included according to the inclusion and exclusion criteria after searching Pubmed and Embase. Overall, an increased risk of severe toxicity in Asian patients with UGT1A1*6 polymorphisms was found. Patients with heterozygous variant of UGT1A1*6 showed an increased risk [odds ratio (OR) = 1.98, 95 % confidence intervals (CI) 1.45-2.71, P < 0.001], and homozygous mutation showed an even higher risk (OR = 4.44, 95 % CI 2.42-8.14, P < 0.001) for severe neutropenia. For severe diarrhea, heterozygous variant of UGT1A1*6 showed no significant risk, while the homozygous variant performed a notable risk (OR = 3.51, 95 % CI 1.41-8.73, P = 0.007). Subgroup meta-analysis indicated that for patients harboring either heterozygous or homozygous variant, low dose of IRI also presented comparably increased risk in suffering severe neutropenia. CONCLUSION: In this meta-analysis, UGT1A1*6 polymorphisms were revealed as potential biomarkers, predicting IRI-induced severe toxicity in patients from Asia, and increased incidences of severe neutropenia could occur in both high/medium and low doses of IRI.

Signaling network assessment of mutations and copy number variations predict breast cancer subtype-specific drug targets.

Individual cancer cells carry a bewildering number of distinct genomic alterations (e.g., copy number variations and mutations), making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here, we performed exome sequencing on several breast cancer cell lines that represent two subtypes, luminal and basal. We integrated these sequencing data and functional RNAi screening data (for the identification of genes that are essential for cell proliferation and survival) onto a human signaling network. Two subtype-specific networks that potentially represent core-signaling mechanisms underlying tumorigenesis were identified. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening, whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes on the basis of genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated.