Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation.

BACKGROUND: Previous studies have shown that microtubule actin crosslinking factor 1 (MACF1) can regulate osteoblast proliferation and differentiation through non-coding RNA (ncRNA) in bone-forming osteoblasts. However, the role of MACF1 in targeting the competing endogenous RNA (ceRNA) network to regulate osteoblast differentiation remains poorly understood. Here, we profiled messenger RNA (mRNA), microRNA (miRNA), and long ncRNA (lncRNA) expression in MACF1 knockdown MC3TC­E1 pre­osteoblast cells. RESULTS: In total, 547 lncRNAs, 107 miRNAs, and 376 mRNAs were differentially expressed. Significantly altered lncRNAs, miRNAs, and mRNAs were primarily found on chromosome 2. A lncRNA-miRNA-mRNA network was constructed using a bioinformatics computational approach. The network indicated that mir-7063 and mir-7646 were the most potent ncRNA regulators and mef2c was the most potent target gene. Pathway enrichment analysis showed that the fluid shear stress and atherosclerosis, p53 signaling, and focal adhesion pathways were highly enriched and contributed to osteoblast proliferation. Importantly, the fluid shear stress and atherosclerosis pathway was co-regulated by lncRNAs and miRNAs. In this pathway, Dusp1 was regulated by AK079370, while Arhgef2 was regulated by mir-5101. Furthermore, Map3k5 was regulated by AK154638 and mir-466q simultaneously. AK003142 and mir-3082-5p as well as Ak141402 and mir-446 m-3p were identified as interacting pairs that regulate target genes. CONCLUSION: This study revealed the global expression profile of ceRNAs involved in the differentiation of MC3TC­E1 osteoblasts induced by MACF1 deletion. These results indicate that loss of MACF1 activates a comprehensive ceRNA network to regulate osteoblast proliferation.

Immunity, Ion Channels and Epilepsy.

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise.

Imaging features of microwave-ablated lesions of the VX2 tumors in rabbit lungs on computed tomography and magnetic resonance images and their correlations with pathological examination.

PURPOSE: This study aimed to explore the accuracy of different imaging methods for lesion volume estimation pre- and post-microwave ablation (MWA) as compared with that of pathological examination. METHODS: We used the VX2 cell line to establish the VX2 lung tumor model in rabbits, followed by MWA of the tumor. The imaging features of the VX2 tumors were documented. The volume of the tumors and the ablated lesions were measured and compared across imaging methods, using the pathological examination as reference. RESULTS: Tumors were successfully developed in 11 rabbits (age, 13.91 ± 1.38 weeks; weight, 2.15 ± 0.56 kg). The mean volume of the tumors was 2.05 ± 1.88 cm3. CT showed the strongest correlation with the pathologic examination results (r = 0.998, p<.001). MWA created three-layered structures that were delineated on MRI. The mean volume of the post-ablation lesion was 10.39 ± 8.93 cm3, and the measurement of the post-ablation volume on 3D-VIBE-T1WI showed the strongest correlation with the pathologic examination results (r = 0.991, p<.001). CONCLUSION: Both CT and MRI are capable of depicting lung tumors. In terms of post-ablation evaluation, MR images could provide more versatile information. The 3D-VIBE-T1WI sequence provides more precise lesion volume evaluation after ablation compared with other methods.

LAMP real-time turbidity detection for fowl adenovirus.

BACKGROUND: Fowl adenovirus (FAdV) is an infectious agent that can cause jaundice, severe anaemia, dyspnoea and reproductive disorders in fowls. Since 2015, FAdV disease has been rapidly spreading among broiler chickens in China, where it has caused significant economic losses. In this study, a loop-mediated isothermal amplification (LAMP) real-time turbidity method with strong specificity to FAdV was established. RESULTS: The established assay was specific to FAdV-4, and the lower limit of detection was 75 copies/µL of extracted DNA. The positive detection rate for the suspected tissue samples was 33.3% (14/42), which was consistent with that of the real-time PCR. CONCLUSION: The proposed LAMP method can quickly and accurately detect prevalent FAdV via real-time turbidity assay, thereby providing a diagnostic platform for the prevention and control of the FAdV disease.

Systems pharmacology approach to investigate the molecular mechanisms of herb Rhodiola rosea L. radix.

Rhodiola rosea L. radix (RRL) is one of the most popular medical herb which has been widely used for the treatment of different diseases effectively, including cardiovascular diseases and nerve system diseases. However, due to the multiple compounds in RRL, the underlying molecular mechanisms of RRL are remained unclear. To decipher the action mechanisms of RRL from a systematic perspective, a systems pharmacology approach integrated absorption, distribution, metabolism, and excretion (ADME) system, drug targeting, and network analysis was introduced. First, by the ADME screening system and the target fishing process, 56 potential active compounds and 62 targets were obtained, respectively. In addition, compound-target network demonstrated that most compounds interacted with multiple targets, indicating that RRL may enhance its therapeutic effects probably through hitting on multiple targets in a holistic level. Moreover, target-pathway network and gene ontology analysis showed that multiple targets of RRL were involved in several biological pathways, i.e. Neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling in cardiomyocytes, and VEGF signaling pathway, which dissecting the therapeutic effects of RRL on various diseases, such as cardiovascular diseases, depression, adaptation diseases, etc. In summary, this work successfully explains the potential active compounds and the multi-scale curative action mechanisms of RRL for treating various diseases; meanwhile, it implies that RRL could be applied as a novel therapeutic agent in arthritic diseases. Most importantly, this work provides an in silico strategy to understand the action mechanisms of herbal medicines from molecular/system levels, which will promote the new drug development of traditional Chinese medicine.

Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via ß-Catenin/TCF1/Runx2 Signaling Axis.

Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory. In this study we identify a novel long noncoding RNA AK045490 which is correlated with osteogenic differentiation and enriched in skeletal tissues of mice. In vitro analysis of bone-derived mesenchymal stem cells (BMSCs) showed that AK045490 inhibited osteoblast differentiation. In vivo inhibition of AK045490 by its small interfering RNA rescued bone formation in ovariectomized osteoporosis mice model. Mechanistically, AK045490 inhibited the nuclear translocation of ß-catenin and downregulated the expression of TCF1, LEF1, and Runx2. The results suggest that Lnc-AK045490 suppresses ß-catenin/TCF1/Runx2 signaling and inhibits osteoblast differentiation and bone formation, providing a novel mechanism of osteogenic differentiation and a potential drug target for osteoporosis.

Propagation of partially coherent four-petal elliptic Gaussian vortex beams in atmospheric turbulence.

The beam spreading and evolution behavior of the intensity profile and coherent vortices of partially coherent, four-petal elliptic Gaussian vortex beams propagating in atmospheric turbulence are studied. The analytical expressions for cross-spectral density function, as well as root mean square (rms) beam width, are derived based on the extended Huygens-Fresnel principle. Results showed that, unlike the partially coherent four-petal Gaussian vortex beams, the partially coherent four-petal elliptic Gaussian vortex beam could change its petal number into six. The dependencies of occurrence, appearance, and transition speed from four- to six-petal profile on the topological charge, the beam order, and the ellipticity factor are illustrated. The far field behaviors of partially coherent four-petal elliptic Gaussian vortex beams propagating in atmospheric turbulence and are compared in free space. Beams with larger topological charge, smaller beam order, and larger ellipticity factor were found to be less influenced by atmospheric turbulence. Further, the ellipticity factor can be used as an additional degree of freedom in controlling the conservation distance of coherence vortices' topological charge.

Prediction of thermodynamically stable Li-B compounds at ambient pressure.

To clarify controversial structures and phase stability in the Li-B system, we predicted energetically favorable compounds and crystal structures of the Li-B binary system at ambient pressure, mainly including Li6B5, LiB2, and LiB3, from ab initio evolutionary structure simulations and further investigated physical properties of stable Li-B compounds using first-principles methods. Metallic Li6B5, predicted in our simulations, has trigonal symmetry with space group R32 and contains linear B chains, but its superconducting Tc is low according to the electron-phonon coupling calculations. Orthorhombic LiB2 (Pnma) and tetragonal LiB3 (P4/mbm) are zero-gap semiconductors; LiB2 is a Dirac semimetal, and both LiB2 and LiB3 are promising thermoelectric materials.

Potential contribution of anammox to nitrogen loss from paddy soils in Southern China.

The anaerobic oxidation of ammonium (anammox) process has been observed in diverse terrestrial ecosystems, while the contribution of anammox to N2 production in paddy soils is not well documented. In this study, the anammox activity and the abundance and diversity of anammox bacteria were investigated to assess the anammox potential of 12 typical paddy soils collected in southern China. Anammox bacteria related to "Candidatus Brocadia" and "Candidatus Kuenenia" and two novel unidentified clusters were detected, with "Candidatus Brocadia" comprising 50% of the anammox population. The prevalence of the anammox was confirmed by the quantitative PCR results based on hydrazine synthase (hzsB) genes, which showed that the abundance ranged from 1.16 × 10(4) to 9.65 × 10(4) copies per gram of dry weight. The anammox rates measured by the isotope-pairing technique ranged from 0.27 to 5.25 nmol N per gram of soil per hour in these paddy soils, which contributed 0.6 to 15% to soil N2 production. It is estimated that a total loss of 2.50 × 10(6) Mg N per year is linked to anammox in the paddy fields in southern China, which implied that ca. 10% of the applied ammonia fertilizers is lost via the anammox process. Anammox activity was significantly correlated with the abundance of hzsB genes, soil nitrate concentration, and C/N ratio. Additionally, ammonia concentration and pH were found to be significantly correlated with the anammox bacterial structure.

Long-term balanced fertilization increases the soil microbial functional diversity in a phosphorus-limited paddy soil.

The influence of long-term chemical fertilization on soil microbial communities has been one of the frontier topics of agricultural and environmental sciences and is critical for linking soil microbial flora with soil functions. In this study, 16S rRNA gene pyrosequencing and a functional gene array, geochip 4.0, were used to investigate the shifts in microbial composition and functional gene structure in paddy soils with different fertilization treatments over a 22-year period. These included a control without fertilizers; chemical nitrogen fertilizer (N); N and phosphate (NP); N and potassium (NK); and N, P and K (NPK). Based on 16S rRNA gene data, both species evenness and key genera were affected by P fertilization. Functional gene array-based analysis revealed that long-term fertilization significantly changed the overall microbial functional structures. Chemical fertilization significantly increased the diversity and abundance of most genes involved in C, N, P and S cycling, especially for the treatments NK and NPK. Significant correlations were found among functional gene structure and abundance, related soil enzymatic activities and rice yield, suggesting that a fertilizer-induced shift in the microbial community may accelerate the nutrient turnover in soil, which in turn influenced rice growth. The effect of N fertilization on soil microbial functional genes was mitigated by the addition of P fertilizer in this P-limited paddy soil, suggesting that balanced chemical fertilization is beneficial to the soil microbial community and its functions.

Multi-perturbation stochastic parallel gradient descent method for wavefront correction.

The multi-perturbation stochastic parallel gradient descent (SPGD) method for adaptive optics is presented in this work. The method is based on a new architecture. The incoming beam with distorted wavefront is split into N sub-beams. Each sub-beam is modulated by a wavefront corrector and its performance metric is measured subsequently. Adaptive system based on the multi-perturbation SPGD can operate in two modes - the fast descent mode and the modal basis updating mode. Control methods of the two operation modes are given. Experiments were carried out to prove the effectiveness of the proposed method. Analysis as well as experimental results showed that the two operation modes of the multi-perturbation SPGD enhance the conventional SPGD in different ways. The fast descent mode provides faster convergence than the conventional SPGD. The modal basis updating mode can optimize the modal basis set for SPGD with global coupling.

Isolation and genetic characterization of avian influenza virus H4N6 from ducks in China.

An avian influenza virus (AIV) strain belonging to the H4 subtype and provisionally designated as A/duck/China/J1/2012(H4N6) was isolated from diseased ducks with respiratory disease at a commercial poultry farm in Shandong, China, in 2012. The genomic coding sequences of all eight segments of this J1 isolate were determined and used for subsequent analysis. Phylogenetic analysis of all eight segments showed that this duck H4N6 virus was of Eurasian lineage and not American lineage. The results show that the virus probably emerged because of a reassortment event involving other avian H4N6 and H6N1 viruses. Interestingly, this H4N6 virus had all the conserved features common to low-pathogenic AIVs, including the HA cleavage sequence, receptor-binding sequences for the 2,3-linked sialic acid receptor in avian species, and the PB2 627E motif. These results suggest that the duck H4N6 isolate could not cross the species barrier to infect and replicate in mammals, including humans. In addition, screening of the duck serum samples showed that only 0.57 % (2/352) of the individuals had weak but measurable hemagglutination inhibition (HI) antibody titers. The low antibody prevalence data were also supported by the failure to detect H4N6 virus (0/56) in clinical nasal swabs of the ducks. These data indicate an alternate reservoir for the H4N6 virus.

Biochar impacts soil microbial community composition and nitrogen cycling in an acidic soil planted with rape.

Biochar has been suggested to improve acidic soils and to mitigate greenhouse gas emissions. However, little has been done on the role of biochar in ameliorating acidified soils induced by overuse of nitrogen fertilizers. In this study, we designed a pot trial with an acidic soil (pH 4.48) in a greenhouse to study the interconnections between microbial community, soil chemical property changes, and N2O emissions after biochar application. The results showed that biochar increased plant growth, soil pH, total carbon, total nitrogen, C/N ratio, and soil cation exchange capacity. The results of high-throughput sequencing showed that biochar application increased α-diversity significantly and changed the relative abundances of some microbes that are related with carbon and nitrogen cycling at the family level. Biochar amendment stimulated both nitrification and denitrification processes, while reducing N2O emissions overall. Results of redundancy analysis indicated biochar could shift the soil microbial community by changing soil chemical properties, which modulate N-cycling processes and soil N2O emissions. The significantly increased nosZ transcription suggests that biochar decreased soil N2O emissions by enhancing its further reduction to N2.

BaC: a thermodynamically stable layered superconductor.

To predict all stable compounds in the Ba-C system, we perform a comprehensive study using first-principles variable-composition evolutionary algorithm USPEX. We find that at 0 K the well-known compound BaC2 is metastable in the whole pressure range 0-40 GPa, while intercalated graphite phase BaC6 is stable at 0-19 GPa. A hitherto unknown layered orthorhombic Pbam phase of BaC has structure consisting of alternating layers of Ba atoms and layers of stoichiometry Ba2C3 containing linear C3 groups and is predicted to be stable in the pressure range 3-32 GPa. From our electron-phonon coupling calculations, the newly found BaC compound is a phonon-mediated superconductor and has a critical superconductivity temperature Tc of 4.32 K at 5 GPa. This compound is dynamically stable at 0 GPa and therefore may be quenchable under normal conditions.

HuR-positive stress granules: Potential targets for age-related osteoporosis.

Aging impairs osteoblast function and bone turnover, resulting in age-related bone degeneration. Stress granules (SGs) are membrane-less organelles that assemble in response to stress via the recruitment of RNA-binding proteins (RBPs), and have emerged as a novel mechanism in age-related diseases. Here, we identified HuR as a bone-related RBP that aggregated into SGs and facilitated osteogenesis during aging. HuR-positive SG formation increased during osteoblast differentiation, and HuR overexpression mitigated the reduction in SG formation observed in senescent osteoblasts. Moreover, HuR positively regulated the mRNA stability and expression of its target ß-catenin by binding and recruiting ß-catenin into SGs. As a potential therapeutic target, HuR activator apigenin (API) enhanced its expression and thus aided osteoblasts differentiation. API treatment increased HuR nuclear export, enhanced the recruitment of ß-catenin into HuR-positive SGs, facilitated ß-catenin nuclear translocation, and contributed osteogenesis. Our findings highlight the roles of HuR and its SGs in promoting osteogenesis during skeletal aging and lay the groundwork for novel therapeutic strategies against age-related skeletal disorders.

Pressure-induced stabilization and insulator-superconductor transition of BH.

Diborane (B(2)H(6)), a high energy density material, was believed to be stable in a wide P, T interval. A systematic investigation of the B-H system using the ab initio variable-composition evolutionary simulations shows that boron monohydride (BH) is thermodynamically stable and can coexist with solid B, H(2), and B(2)H(6) in a wide pressure range above 50 GPa. B(2)H(6) becomes unstable and decomposes into the Ibam phase of BH and H(2) (C2/c) at 153 GPa. The semiconducting layered Ibam structure of BH at 168 GPa transforms into a metallic phase with space group P6/mmm and a 3D topology with strong B-B and B-H covalent bonds. The Ibam-P6/mmm transformation pathway suggests the possibility of obtaining the metastable Pbcm phase on cold decompression of the P6/mmm phase. The electron-phonon coupling calculations indicate that P6/mmm-BH is a phonon-mediated superconductor with a critical temperature of superconductivity (T(c)) of 14.1-21.4 K at 175 GPa.

Effect of long-term wastewater irrigation on potential denitrification and denitrifying communities in soils at the watershed scale.

Wastewater irrigation mitigates the problem of water shortage but leads to the potential accumulation of pollutants and causes corresponding changes in denitrifying communities and denitrification, hence the potential ecological risk of long-term wastewater irrigation should not be overlooked. We investigated the relative contributions of different environmental factors to the abundance and diversity of denitrifying communities harboring nirK, nirS, and nosZ genes and the relative importance of these biotic and abiotic variables in potential denitrification activity (PDA) in soils with wastewater irrigation for around 25 years at a large watershed scale. Results showed that soil physicochemical properties, pollutants, including heavy metals and PAHs, and vegetation are the major factor groups influencing the abundance and structure of the three denitrifying communities and PDA. NirK-, nirS-, or nosZ-harboring denitrifiers responded in different manners to environmental changes, and were mainly influenced by substrate concentration, carbon source, or pollutants, respectively. The structure of the three denitrifying communities was more relevant to the environmental changes than their abundance. Conversely, the abundance, rather than diversity, was correlated with PDA. Pollutants and vegetation could affect PDA by both direct and indirect paths through soil physicochemical properties including pH, carbon and nitrogen sources, or through the abundance of denitrifying functional genes. The abundance of denitrifying functional genes is a valuable index that integrates potential activity and various environmental factors, and is therefore a good predictor of denitrification in the presence of environmental changes.

MiR-12200-5p Targets Multiple Members of Wnt Signaling Pathway to Inhibit Osteoblast Differentiation and Bone Formation.

BACKGROUND: Osteoporosis is widespread and has become an emerging problem in the elderly. MicroRNAs could affect osteoblast differentiation and further regulate the occurrence of osteoporosis by targeting osteogenic differentiation signaling pathways. Our screening study found that miR-12200-5p simultaneously targeted six important factors within the Wnt signaling pathway (Apc, Tcf4, Tcf7, Wnt3a, Wnt5a, and Lrp6), indicating that miR-12200-5p might function as a strong regulator of this pathway. Since the Wnt pathway exists as one of the most essential pathways for osteogenic differentiation, miR-12200-5p may have an important role in the development of osteoporosis. OBJECTIVE: This study intended to explore the regulatory role and corresponding mechanism of miR-12200-5p in osteoblast differentiation. METHODS: We investigated the differentiation of osteoblast after the treatments of miR-12200-5p mimic and inhibitor. The interactions between miR-12200-5p and its target genes were also detected. Furthermore, the rescue effect of miR-12200-5p inhibitor on osteoporosis was evaluated using an ovariectomized osteoporosis mouse model. RESULTS: MiR-12200-5p significantly inhibited osteoblast differentiation, and bound with the 3'-UTR sequences of its target genes (Apc, Tcf4, Tcf7, Wnt3a, Wnt5a, and Lrp6) to reduce the expressions of these genes. The inhibition of miR-12200-5p would almost fully alleviate postmenopausal osteoporosis. CONCLUSION: MiR-12200-5p could strongly repress osteoblast differentiation and bone formation by targeting multiple members of the Wnt signaling pathway simultaneously. The study supplemented the theoretical and experimental basis for researching the mechanism of osteogenic differentiation and inspired the development of novel therapeutic strategies for osteoporosis.

Nitrous oxide emissions from tea plantations: A review.

Tea plantations are an important N2O source. Fertilizer-induced N2O emission factors of tea plantations are much higher than other upland agricultural ecosystems. According to the basic information on characteristics and knowledge of N2O emissions from tea plantations around the world, we comprehensively reviewed N2O emission characteristics, production process, influencing factors, and reduction measures from tea plantations. The global means of ambient N2O emission and N2O emission stimulated by nitrogen fertilizer application from tea plantations were (2.68±2.92) kg N·hm-2 and (11.29±9.45) kg N·hm-2, respectively. The fertilizer-induced N2O emission factor in tea plantations (2.2%±2.1%) was much higher than the IPCC-estimated N2O emission factor for agricultural land (1%). N2O emission from tea plantation soil (a typical acid soil) were mainly produced during nitrification and denitrification, with denitrification being dominant. N2O emission from tea plantations were significantly related to the amount of fertilizer application. Other factors, such as fertilizer type, could also affect soil N2O emissions in tea plantations. The main reduction methods of N2O emission from tea plantations included optimizing the amount and type of fertilizer, amending biochar, and rationally using nitrification inhibitors. In future, we should strengthen in-situ observations of soil N2O emission from tea plantations at both temporal and spatial scales, combine lab incubation and field studies to elucidate the mechanisms underling tea plantation soil N2O emissions, and use a data-model fusion approach to reduce uncertainties in the estimation of global N2O emission. These would provide theoretical support and practical guidance for reasonable N2O emission reduction in tea plantations.

Research progress in biological control of tomato bacterial wilt.

Bacterial wilt caused by the infection of Ralstonia solanacearum, is one of the most harmful diseases to tomatoes, one of the most important greenhouse vegetables in China. R. solanacearum can survive and remain active in the deep soil for a long time, and the chemical control of tomato bacterial wilt is consequently limited. In this study, we introduced the characteristics of tomato bacterial wilt disease and the types of R. solanacearum, and systematically reviewed the research progresses of biological control methods from the aspects of botanical insecticides, agricultural antibiotics, biocontrol bacteria. We emphatically introduced the principle and current status of these methods, discussed the limitations and the improvement strategies, and prospected a new environmental protection and efficient biological control system based on micro-ecological regulation would be the development direction of biological control of tomato bacterial wilt.