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Background: In the era of antiretroviral therapy (ART), central nervous system (CNS) complications in patients with human immunodeficiency virus (HIV) infection are sometimes associated with cerebrospinal fluid (CSF) viral escape. Here, we reported a case of persistent CNS viral escape with recurrent symptomatic encephalitis, which had ultimate stabilization achieved by a combination of ART adjustment and corticosteroids. Case presentation: A 27-year-old man with HIV infection complained of recurrent headaches during the last year. His magnetic resonance imaging (MRI) presented diffused bilateral white matter lesions, and laboratory tests confirmed elevated CSF protein level, lymphocytic pleocytosis, and detectable CSF HIV RNA (774 copies/mL). Plasma HIV RNA was well suppressed with tenofovir, lamivudine, and lopinavir/ritonavir. Prednisone 60 mg once daily was initiated to reduce intracranial inflammation, followed by a good clinical response, with CSF HIV RNA still detectable (31.1 copies/mL). During the gradual tapering of prednisone, his headache relapsed, and booming viral loads were detected in both CSF (4580 copies/mL) and plasma (340 copies/mL) with consistent drug-resistant mutations. Thereupon, prednisone was resumed and the ART regimen was switched to zidovudine, lamivudine, and dolutegravir according to drug resistance tests. Persistent clinical recovery of symptoms, neuroimaging, and laboratory abnormalities were observed in the follow-up visits. Conclusion: CSF and plasma HIV RNA and further drug resistance tests should be monitored in HIV-infected patients with neurologic symptoms, as opportunistic infections or tumors can be ruled out. ART optimization using a sensitive regimen may be crucial for addressing CSF viral escape and the related encephalitis. [ABSTRACT FROM AUTHOR]

Clustering is a basic task of data analysis and decision making. Recently, graph convolution network (GCN) based deep clustering frameworks have produced the state-of-the-art performance. However, the traditional GCN has not fully learnt the structural information of the neighbors. Therefore, in this paper, we propose an attention-based hierarchical denoised deep clustering (AHDDC) algorithm to solve the problem, which enables GCN to learn multiple layers of hidden information and uses the attention mechanism to strengthen the information. Besides, we use a denoising autoencoder to reduce the influence of the data noise on the clustering. In AHDDC, Firstly, we input the feature vector of the original data into a denoising autoencoder (DAE) to learn the hidden representation; secondly, the representation information of the autoencoder and the structure information constructed by the KNN graph are passed into a hierarchical attentional graph convolutional network; finally, a self-supervision module is used to optimize the clustering results. Experimental results show the superiorities of our method over most advanced algorithms. Besides, the effectiveness of the proposed hierarchical, attention based and denoising improving strategies are also verified experimentally. [ABSTRACT FROM AUTHOR]

Stress relaxation, the decreasing trend of stress at a given strain along with time, is an essential mechanical behavior for any structural material. Graphene fiber (GF), a new kind of carbonaceous fiber, has emerged prominent mechanical performance and multifunctionality since first invented in 2011. However, most of efforts were focused on the improvement of mechanical strength and electrical/thermal conductivity and dynamic mechanical behavior has been ignored. Here, we studied the stress relaxation behavior of GF and revealed a severe stress drop for nascent GF. We found that the drop in stress during relaxation decreased with the promotion of the orientation degree and crystallinity. Plasticization stretching strategy and graphitization process were presented to relieve the relaxation of GF, accompanying with excellent mechanical strength. The optimized GF exhibits best stress relaxation property with 99% stress remained after relaxation. This work reveals an essential relaxation behavior of GFs and develops effective processes to conquer stress relaxation, making GFs for practical applications as structural materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner. [ABSTRACT FROM AUTHOR]

Textiles with excellent electromagnetic interference (EMI) shielding properties are highly desirable to prevent interference between electronic devices and ensure their stable service in this era of serious electromagnetic radiation. However, prevalent method to prepare EMI shielding textiles focused on decorating conductive nanomaterials onto insulative textile, limiting the performance of textiles. Here, we directly weave highly conductive graphene fiber (GF) tows to obtain a GF textile with high EMI shielding performance. The electrical conductivity of GFs is improved by the restored conjugate structure and optimized crystallinity through efficient thermal annealing. An X-band EMI shielding effectiveness (SE) for GF textile of more than 90 dB is achieved owing to the high electrical conductivity of 8.5 × 105 S m−1 of GF. Overlapping two layers of textile weaved by GF yields an SE of more than 120 dB. Moreover, the woven GF textiles exhibit excellent durability of bending and pressing. Combined with the outstanding EMI shielding performance, the GF textiles show great potential for applications in wearable devices, communication, defense, and the Internet of Things. [Display omitted] • Highly conductive graphene fiber (GF) tows are woven to obtain a GF textile. • The greatly restored graphene structure makes GF highly conductive thus awarding GF textiles high EMI shielding performance. • The durable GF textiles have broad application prospects. [ABSTRACT FROM AUTHOR]

Purpose: DCP is a useful HCC tumor marker, which reflects a defect in vitamin K metabolism. We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also.Experimental Design: HCC patients who had both elevated AFP and DCP were included. A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose.Results: A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose. No toxicities were found up to 1,000 mg/infusion. In the phase II cohort, 93% of patients had tumor marker responses by decreased DCP levels, but only 22% had responses by decreased AFP levels. CT scans showed 11% of patients had PRs, 59% had stable tumors and 29.6% had tumor progression. Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis.Conclusions: Vitamin K1 was non-toxic at high doses, strongly inhibited plasma DCP levels, but weakly suppressed AFP levels. The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth, as DCP levels were decreased in patients without AFP change, and were suppressed in vitro at 1% of the vitamin K1 concentration needed to inhibit AFP. [ABSTRACT FROM AUTHOR]

A synthetic vitamin K analog, compound 5 (Cpd 5), is a potent inhibitor of cell growth. The aim was to investigate whether c-Myc was involved in Cpd 5-induced cell growth inhibition.Human hepotoma cells (Hep 3B) were cultured and treated with Cpd 5, and c-Myc protein expression and phosphorylation were investigated using Western blot analysis.Cpd 5 was found to inhibit c-Myc protein expression and induce c-Myc phosphorylation in Hep 3B cells. The phosphorylation of c-Myc was induced by both Cpd 5-mediated persistent extracellular signal-regulated kinase (ERK) phosphorylation and Cpd 5 increased glycogen synthase kinase-3 (GSK-3) activity. When using GSK-3 inhibitor, SB216763, c-Myc phosphorylation was significantly decreased and c-Myc levels were restored in Cpd 5 treated cells, suggesting that Cpd 5-mediated increase of GSK-3 activity enhanced c-Myc degradation and resulted in reduction of c-Myc levels. The lower c-Myc levels were found to cause altered expression of two c-Myc target genes, growth arrest gene gadd45 and ornithine decarboxylase (ODC).The results suggest that Cpd 5-mediated c-Myc phosphorylation resulted in enhanced c-Myc protein degradation and reduced c-Myc protein levels, which may contribute to cell growth inhibition by Cpd 5. [Copyright &y& Elsevier]

A comparison was made between two K vitamin analogs. Growth in vitro of Hep G2 hepatoma cells was inhibited both by Compound 5 (Cpd 5), a recently synthesized thioalkyl analog of vitamin K or 2-(2-mercaptoethanol)-3-methyl-1, 4-naphthoquinone, as well as by synthetic vitamin K3 (menadione). Using synchronized Hep G2 hepatoma cells, the actions of both Cpd 5 and vitamin K3 on cell cycle regulating proteins were examined. Cpd 5 decreased the levels of cyclin D1, Cdk4, p16, p21 and cyclin B1. By contrast, VK3 only decreased the level of cyclin D1, but had no effect on the levels of Cdk4, p16 or p21. Interestingly, both VK3 and VK2 increased the levels of p21. The naturally occurring K vitamins had little effect on cell growth and none on the cyclins or Cdks. Amounts and activity of the G1/S phase controlling Cdc25A were measured. We found that Cpd 5 directly inhibited both Cdc25A activity and its protein expression, whereas VK3 did not. Thus, the main effects of Cpd 5 were on G1 and S phase proteins, especially Cdk4 and Cdc25A amounts in contrast to VK3. Computer docking studies of Cpd 5 and VK3 to Cdc25A phosphatase showed three binding sites. In the best conformation, Cpd 5 was found to be closer to the enzyme active site than VK3. These findings show that Cpd 5 represents a new class of anticancer agent, being a protein tyrosine phosphatase (PTP) antagonist, that binds to Cdc25A with suppression of its activity. Tumors expressing high levels of oncogenic Cdc25A phosphatase may thus be susceptible to the growth inhibitory activities of this class of compound. [Copyright &y& Elsevier]

Thioalkyl containing K vitamin analogs have been shown to be potent inhibitors of hepatoma cell growth and antagonizers of protein tyrosine phosphatase activity. We now show that they inhibit the activity of specific protein tyrosine phosphatases (PTP) in cell-free conditions in vitro, particularly the dual specificity phosphatase Cdc25A. Using primary cultures of adult rat hepatocytes that are in G0/G1 phase until stimulated into DNA synthesis by epidermal growth factor, we found that 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or Compound 5 (Cpd 5) inhibited hepatocyte DNA synthesis and PTP activity in cell culture and in vivo after a two-thirds partial hepatectomy. We found a selective inhibition of Cdc25A activity in vitro, using both synthetic substrates and authentic cellular substrate, immunoprecipitated phospho-Cdk4. Intact Cpd 5-treated cells had decreased cellular Cdc25A activity and increased tyrosine phosphorylation of Cdk4, resulting in decreased phosphorylation of retinoblastoma (Rb). Loss of Cdk4 activity was confirmed using Cdk4 immunoprecipitates from either Cpd 5-treated or untreated cells and measuring its kinase activity using GST-Rb as target. We found a similar order of activity for inhibition of growth and Cdc25A activity using several thiol-containing analogs. Cdc25A inhibitors may thus be useful for defining biochemical pathways involving protein tyrosine phosphorylation that mediate cell growth inhibition. [Copyright &y& Elsevier]

Background/Aims: Compound 5 (Cpd 5), a vitamin K analog, inhibits rat hepatocyte DNA synthesis and hepatoma cell growth. The aim of this study was to determine if the inhibitory effect of Cpd 5 on cell growth was related to apoptosis.Methods: Isolated rat hepatocytes were cultured with Cpd 5, and mitogen-activated signaling pathway and apoptosis pathway were investigated using Western blot analysis.Results: When rat hepatocytes were cultured with Cpd 5 for 48 h, apoptosis was evident, which included characteristic morphological changes, DNA fragmentation, and the activation of caspase 3 (CPP 32)-like protease. Examination of upstream events of apoptosis pathway showed that the expression of Bax was induced and bcl-2 was inhibited by Cpd 5 treatment. Concomitant with the induction of apoptosis, Cpd 5 activated the extracellular signal-regulated kinase (ERK) signaling pathway. PD 98059, a mitogen-activated protein kinase kinase inhibitor, and glutathione, an anti-thiol-oxidant, not only blocked Cpd 5-induced ERK phosphorylation, but also antagonized the activation of CPP-32, the altered Bcl-2/Bax expression, and DNA fragmentation.Conclusions: The data suggest that the ERK signaling pathway may be involved in the regulation of rat hepatocyte apoptosis induced by Cpd 5. [Copyright &y& Elsevier]

By studying dynamic characteristics of the leaf spring system, a new elastic component is designed to reduce the working load and to a certain extent to ensure the linearity as well as increase the amplitude in the vertical and horizontal directions in vibration screen. The modal parameters, amplitudes, and amplification factors of the leaf spring system are studied by simulation and experiment. The modal results show that the leaf spring system vibrates in horizontal and vertical directions in first and second mode shapes, respectively. It is conducive to loosening and moving the particles on the vibration screen. In addition, it is found that the maximum amplitude and amplification factor in the horizontal direction appear at 300 r/min (5 Hz) while those in the vertical direction appear at 480 r/min (8 Hz), which are higher than those in the disc spring system. Moreover, the amplitude of the leaf spring system increases proportionally with the increase of exciting force while the amplification factors are basically the same under different exciting forces, indicating the good linearity of the leaf spring system. Furthermore, the minimum exciting force occurs in the leaf spring system under the same amplitude by comparing the exciting force among different elastic components. The above works can provide guidance for the industrial production in vibration screen. [ABSTRACT FROM AUTHOR]

In this work, the influences of constraint modes and the number of disc springs on the dynamic characteristics of the disc spring system are studied by simulation and experiment. The amplitudes and amplification factors of the disc spring system under different constraint modes and different numbers of disc springs are obtained. The results show that the maximum amplitude and amplification factor both appear at the constraint modes of locking and no preloading, which indicates that the locking and no preloading is the best constraint mode among the four different constraint modes. Moreover, the amplitude of the disc spring system first increases and then decreases with the number of disc springs increasing, while the amplification factor increases with the number of disc springs increasing. The maximum amplification factor (10.21 in experiment) of the disc spring system appears at 10 disc springs. By studying the relationship between the number of disc springs and amplification factor and damping, we find that the damping of the disc spring system can be reduced by increasing the disc spring numbers, and thus, the corresponding amplification factor can be improved. Furthermore, as the number of disc spring increases, the height differences of disc springs before and after locking are all close to 3 mm, which indicates that the amount of locking compression in the assembly process has a good consistency when the number of disc springs changes. The aforementioned works can provide guidance for the industrial production in screen vibration. [ABSTRACT FROM AUTHOR]

To avoid too large exciting force in traditional linear vibrating screen and unstable working state in resonance screen, the disc spring system is applied in the linear vibration screen. The model of the disc spring system in vibration screen is established by simulation and experiment. The characteristics of modal and amplitude of the disc spring system in vibration screen are studied. We found that the disc spring system vibrates in vertical direction at the third-order natural frequency, which is consistent with the direction of the vibration screen when screening particles. Moreover, the third-order natural frequencies in simulation and experiment are basically consistent. Furthermore, the maximum amplitude of the disc spring system appears at 960 r/min (16 Hz), which is in accord with the third-order natural frequency. Meanwhile, the amplitude increases proportionally with the increase of exciting force, while the amplification factors are the same under three different exciting forces. This indicates that the disc spring system has excellent linearity. The results of research provide guidance for design and application of elastic components on the vibration screen. [ABSTRACT FROM AUTHOR]

Highlights: Presenting the first investigation into the structurally bubbling-failure mechanism of graphitic film during cyclic liquid nitrogen shocks. Proposing an innovative design about seamless heterointerface constructing a Cu-modified structure. Inventing a new ultra-stable species of highly thermally conductive films to inspire new techniques for efficient and extreme thermal management. Highly thermally conductive graphitic film (GF) materials have become a competitive solution for the thermal management of high-power electronic devices. However, their catastrophic structural failure under extreme alternating thermal/cold shock poses a significant challenge to reliability and safety. Here, we present the first investigation into the structural failure mechanism of GF during cyclic liquid nitrogen shocks (LNS), which reveals a bubbling process characterized by "permeation-diffusion-deformation" phenomenon. To overcome this long-standing structural weakness, a novel metal-nanoarmor strategy is proposed to construct a Cu-modified graphitic film (GF@Cu) with seamless heterointerface. This well-designed interface ensures superior structural stability for GF@Cu after hundreds of LNS cycles from 77 to 300 K. Moreover, GF@Cu maintains high thermal conductivity up to 1088 W m−1 K−1 with degradation of less than 5% even after 150 LNS cycles, superior to that of pure GF (50% degradation). Our work not only offers an opportunity to improve the robustness of graphitic films by the rational structural design but also facilitates the applications of thermally conductive carbon-based materials for future extreme thermal management in complex aerospace electronics. [ABSTRACT FROM AUTHOR]

Exploring and understanding the structure‐mechanical property relations in hierarchical graphene assemblies is crucial for optimizing their mechanical properties and developing new functionalities, as the tensile strength is two orders of magnitude degradation from pristine graphene to graphene assemblies. Yet, quantifying the strength degradation across multiscale is a challenge due to the complex hierarchical structures. Thus, key structures and dominated factors at different lengthscales that affect the mechanical properties of graphene assemblies should be extracted for the reasonable unveiling of this problem. In this study, the multiscale mechanical degradation of graphene assemblies through practical microstructure‐guided multiscale modeling is characterized. Combining with experimental observations, three representative models are developed to study the mechanical behaviors of graphene assemblies at different lengthscales. Then, the dominated factors affecting the strength at these lengthscales are identified, that is the defects in monolayer graphene, tension‐shear load transfer for stacked graphene, and uniformity of graphene assemblies. Based on the simulation results, the structure‐strength relation of graphene assemblies is given, and practical strategies are proposed followed by experimental realization, to significantly improve the mechanical properties of graphene‐based nanocomposites. [ABSTRACT FROM AUTHOR]

Disordered wrinkles inevitably appear in the fluid assembly process of graphene and heavily depress performances of assembled graphene papers. Achieving high plasticity enables the post modulation to rearrange wrinkles by stretching. Here, we obtain an over 100% improved plasticity by intercalating oligomer into graphene oxide (GO) laminates and fabricate strong, stiff and conductive graphene papers (GPs) via post stretching. The intercalated oligomer activates the mobilization of GO sheets and achieves high plasticity of solid GO papers. The improved plasticity allows high stretching ratio and the post-stretched GP features regular orientation (0.95) of graphene sheets and aligned fine wrinkles. The crystalline GPs have a high tensile strength up to 1.3 GPa, Young's modulus of 92.9 GPa and highly electrical conductivity (1.05 × 105 S m−1). The greatly improved plasticity by oligomer extends the processing capability of graphene materials and the strong and conductive GP can be assembled in high performance nanocomposites with excellent electromagnetic interference shielding effectiveness (EMI SE). [Display omitted] • Intercalating oligomer greatly enhances plasticity of graphene oxide laminates for the improved interlayer friction. • The greatly enhanced plasticity enables to efficiently eliminate disordered wrinkles of assembled graphene sheets. • The crystalline graphene paper (GP) exhibits superior mechanical and electrical properties. • The (GP-based) laminated composite shows high tensile strength and electromagnetic interference shielding effectiveness. [ABSTRACT FROM AUTHOR]

The unique, plate-like morphology of hydroxyapatite (HAP) nanocrystals in bone lends to the hierarchical structure and functions of bone. Proteins enriched in phosphoserine (Ser-OPO3) and glutamic acid (Glu) residues have been proposed to regulate crystal morphology; however, the atomic-level mechanisms remain unclear. Previous molecular dynamics studies addressing biomineralization have used force fields with limited benchmarking, especially at the water/mineral interface, and often limited sampling for the binding free energy profile. Here, we use the umbrella sampling/weighted histogram analysis method to obtain the adsorption free energy of Ser-OPO3 and Glu on HAP (100) and (001) surfaces to understand organic-mediated crystal growth. The calculated organic-water-mineral interfacial energies are carefully benchmarked to density functional theory calculations, with explicit inclusion of solvating water molecules around the adsorbate plus the Poisson-Boltzmann continuum model for long-range solvation effects. Both amino acids adsorb more strongly on the HAP (100) face than the (001) face. Growth rate along the [100] direction should then be slower than in the [001] direction, resulting in plate-like crystal morphology with greater surface area for the (100) than the (001) face, consistent with bone HAP crystal morphology. Thus, even small molecules are capable of regulating bone crystal growth by preferential adsorption in specific directions. Furthermore, Ser-OPO3 is a more effective growth modifier by adsorbing more strongly than Glu on the (100) face, providing one possible explanation for the energetically expensive process of phosphorylation of some proteins involved in bone biomineralization. The current results have broader implications for designing routes for biomimetic crystal synthesis. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A microfluidic device with a microvalve incorporated with intelligent giant electrorheological fluid (GERF) was proposed to actively and accurately control micro-droplet merging in various droplet scales. The GERF is a suspension without an additional electric field, and its viscosity can be increased with the increase in the voltage. A chamber composed of an expanded channel with thin membranes on both sides and several pillars is used to realize droplet merging. The chamber can restrict droplet flow to ensure droplet contact. When the pressure is applied by the microvalve, the membranes would pump up to the merging chamber. Thus, the pressure difference between the merging chamber and GERF channel could be controlled by the membranes' deformation and influence the merging of the droplets. Therefore, the number of merged droplets from zero to five can be controlled when the flow rate of both the continuous phase and the discrete phase was 0.5 µl/min or from four to zero when the flow rate of the continuous phase was 0.8 µl/min and the discrete phase was 0.2 µl/min. The micro-chip can be easily fabricated without complex equipment, and only a pair of electrodes are required to control the microvalve. Thus, the proposed device has excellent application prospects in chemical synthesis and single-cell analysis. [ABSTRACT FROM AUTHOR]

Graphene fiber (GF), a macroscopic one‐dimensional assembly of individual graphene sheets, promises both extraordinary mechanical performance and superior multifunctionality. However, the properties of graphene fiber are still limited due to the unfavorable crystalline structures, especially induced by wrinkled conformations of graphene. A plasticization spinning strategy is presented to achieve GF with both high mechanical strength and electrical/thermal conductivity. Adjusting the interlayer space from 1.2 to 1.8 nm by intercalating proper plasticizers to adjacent graphene oxide sheets enables graphene oxide fibers to achieve a 580% enhanced deformable plasticity. Such a plasticization spinning flattens random graphene wrinkles, and regulates sheets with high order and stacking density, thereby forming large crystallite domains. The GF exhibits all around record performance including mechanical strength (3.4 GPa), electrical conductivity (1.19 × 106 S m−1), and thermal conductivity (1480 W m−1 K−1). The optimally crystalline GF with the integration of benchmark overall properties and scalable fabrication is likely to be attractive and competitive in future industrial applications. [ABSTRACT FROM AUTHOR]

The p38MAPKs (mitogen-activated protein kinases) signaling contributes a pivotal role in mammalian ovarian follicular development; however, the knowledge regarding their expression in geese remains unresolved. The objective of the current study was to determine the spatio-temporal expression of heat shock protein 27 (HSP27) and mitogen- and stress-activated protein kinase 1 (MSK1) genes in the prehierarchical follicles during geese ovarian development. The prehierarchical follicles samples were harvested from 35- to 37-week-old healthy laying geese. HSP27 and MSK1 relative expression in various sized prehierachical follicles was detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Follicular wall localization of HSP27 and MSK1 was examined by using immunohistochemistry. Our results at mRNA level indicated that HSP27 was highly expressed in middle white follicles whereas MSK1 was predominantly expressed in small white follicles. The western blotting results for HSP27 and MSK1 were inconsistent with the RT-qPCR results in various stages of prehierachical follicular development but noticeably, HSP27 proteins were still expressed more in middle white follicles while MSK1 proteins were more abundant in primary follicles. At different stages of prehierarchical development, immunodetections in the granulosa and theca cells revealed that HSP27 was intensively localized in middle white follicles while strong detections of MSK1 were observed in large white follicles. These results indicate HSP27 and MSK1 might be associated to the key regulators of folliculogenesis in geese. [ABSTRACT FROM AUTHOR]

The unavoidable defects in the structure of carbon-graphite composites, such as microcracks, have severe effects on their behaviors and performances in application. The introduction of graphene in carbon-graphite materials is considered as an effective strategy to regulate their structures and properties. Here, sulfonated graphene with abundant sulfonic acid groups was introduced into ultrafine petroleum coke powders, which could effectively prevent and reduce the generation of microcracks during preparation process of carbon-graphite composite. As a consequent, the prepared composites reinforced by doping 1 wt% of sulfonated graphene demonstrate obviously enhanced mechanical properties with flexural and compressive strength of 57.5 ± 3.8 MPa and 121.0 ± 2.3 MPa, respectively, which is 2.5 times higher than that of pure carbon-graphite counterparts. It indicates that the addition of sulfonated graphene as carbon reinforcement in carbon-graphite composites effectively improve interaction between tar pitch and coke powders, which increases the carbonized degree in roasting process, thus substantially polish up the structure integrity and the performance of carbon-graphite composites. Image 1 [ABSTRACT FROM AUTHOR]

The critical role of the self-assembled structure of collagen in skeletal mineralization is long recognized, yet the angstrom to tens of nanometers length-scale nucleation mechanism of calcium phosphate mineral (Ca–P i ) remains unclear. Here, by constructing three-dimensional structure of collagen fibril, we report direct computational evidence of intrafibrillar Ca–P i nucleation in the collagen matrix and illustrate the crucial role of charged amino acid sidechains of collagen molecules in nucleation. The all-atom Hamiltonian replica exchange molecular dynamics simulation shows that these charged sidechains are oriented toward the fibril “hole zones” and significantly template nucleation with amorphous Ca–Pi phase, ∼1.3–1.6 nm in size, thus explaining the empirical observations that Ca–P i nucleates principally in these regions. We also show that the low water density of about 0.70 g cm −3 in these zones may further benefit nucleation by lowering the enthalpic penalty for ion desolvation. This work provides insight, at the atomistic level, into the nucleation mechanism of bone crystals within a collagen matrix for understanding mineral deposition, interpreting mineralization experiments and guiding the design of new implantable materials. [ABSTRACT FROM AUTHOR]

mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. Although cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5′ UTRs impacts protein synthesis at the level of initiation. 5′ UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed that ac4C in the −1 position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner. [Display omitted] • mRNA acetylation impacts translation in a position-dependent manner • 5′ UTR ac4C promotes upstream initiation and inhibits canonical start codons • ac4C within Kozak sequences structurally alters the interaction with tRNA i Met • ac4C within mRNA CDSs enhances translation mRNA modifications alter canonical nucleobase behavior. Arango et al. show that a single modification, ac4C, influences mRNA translation in a position-dependent manner. ac4C within coding sequences promotes elongation, whereas 5′ UTR ac4C inhibits initiation through the generation of repressive structures and through the direct modulation of tRNA i Met interactions. [ABSTRACT FROM AUTHOR]

Abstract: Most hepatomas have a defect in prothrombin carboxylation, and can secrete under-carboxylated prothrombin or des-γ-carboxy-prothrombin (DCP), the function of which is unknown. We considered that the prothrombin-DCP axis might also be involved in growth control. Hepatocytes and hepatoma cells were treated with prothrombin and DNA synthesis and cytoskeletal changes were studied. Prothrombin inhibited DNA synthesis in hepatocytes on fibronectin, but not collagen matrix. Hepatoma cell lines were not inhibited. We found that hepatoma cell matrix conferred resistance to hepatocytes. Prothrombin decreased fibronectin but not collagen amounts, but only in the presence of hepatocytes and not hepatoma cells, indicating that it has a differential action on matrix proteins. It also caused changes in cell shape and actin depolymerization. In vivo, there was a decrease in plasma prothrombin activity after a partial hepatectomy (PH), concomitant with the peak of DNA synthesis in the hepatocytes at 24h after PH. Injection of warfarin at the time of PH, further inhibited PT activity and enhanced this 24h peak of DNA synthesis. Furthermore, repeated injection of prothrombin lowered the peak DNA synthesis after PH. The data support the hypothesis that prothrombin can act as a hepatocyte growth inhibitor, likely at the level of fibronectin loss and result in cytoskeletal changes. Hepatomas resist this action, possibly due to their different matrix proteins. This represents a novel mechanism for growth regulation and provides a possible biological significance for the tumor marker DCP. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) or hepatoma cells have impaired ability to perform vitamin K-dependent carboxylation reactions. Vitamin K can also inhibit growth of HCC cells in vitro. Both carboxylation and growth inhibition are vitamin K dose dependent. We used rat hepatocytes, a vitamin K-growth sensitive (MH7777) and a vitamin K-growth resistant (H4IIE) rat hepatoma cell line to examine vitamin K uptake and vitamin K-mediated microsomal carboxylation. We found that vitamin K is taken up by normal rat hepatocytes against a saturable concentration gradient. The relative rates of uptake by rat hepatocytes and the two rat cell lines MH7777 and H4IIE correlated with their sensitivity to vitamin K-mediated cell growth inhibition. Pooled hepatocytes from liver nodules from rats treated with the hepatocarcinogen diethylnitrosamine (DEN) also had a reduced rate of vitamin K uptake. However, using a cell-free system, microsomes from both normal rat hepatocytes and the two rat hepatoma cell lines had a similar ability to support carboxylation mediated by exogenously added vitamin K. The results support the hypothesis that different sensitivity of hepatoma cells to vitamin K may be due to differences in vitamin K uptake and may be unrelated to the actions of vitamin K on carboxylation. [Copyright &y& Elsevier]