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Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1β, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1β-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-ɑ. Furthermore, we revealed that LDC067 inhibited IL-1β-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA. • CDK9 is upregulated in osteoarthritis cartilage and is correlated with the severity of OA. • The specific inhibitor of CDK9, LDC067 attenuates the catabolism and hypertrophic changes of chondrocytes in vitro. • LDC067 suppresses the activation of the NF-κB signaling pathway. • LDC067 ameliorates OA cartilage destruction in vivo and may be a novel therapeutic agent. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the effectiveness of using the torsional vibration signal as a diagnostic tool for planetary gearbox faults detection. The traditional approach for condition monitoring of the planetary gear uses a stationary transducer mounted on the ring gear casing to measure all the vibration data when the planet gears pass by with the rotation of the carrier arm. However, the time variant vibration transfer paths between the stationary transducer and the rotating planet gear modulate the resultant vibration spectra and make it complex. Torsional vibration signals are theoretically free from this modulation effect and therefore, it is expected to be much easier and more effective to diagnose planetary gear faults using the fault diagnostic information extracted from the torsional vibration. In this paper, a 20 degree of freedom planetary gear lumped-parameter model was developed to obtain the gear dynamic response. In the model, the gear mesh stiffness variations are the main internal vibration generation mechanism and the finite element models were developed for calculation of the sun-planet and ring-planet gear mesh stiffnesses. Gear faults on different components were created in the finite element models to calculate the resultant gear mesh stiffnesses, which were incorporated into the planetary gear model later on to obtain the faulted vibration signal. Some advanced signal processing techniques were utilized to analyses the fault diagnostic results from the torsional vibration. It was found that the planetary gear torsional vibration not only successfully detected the gear fault, but also had the potential to indicate the location of the gear fault. As a result, the planetary gear torsional vibration can be considered an effective alternative approach for planetary gear condition monitoring. [ABSTRACT FROM AUTHOR]

This paper presents a new gear dynamic model for flexibly supported gear sets aiming to improve the accuracy of gear fault diagnostic methods. In the model, the operating gear centre distance, which can affect the gear design parameters, like the gear mesh stiffness, has been selected as the iteration criteria because it will significantly deviate from its nominal value for a flexible supported gearset when it is operating. The FEA method was developed for calculation of the gear mesh stiffnesses with varying gear centre distance, which can then be incorporated by iteration into the gear dynamic model. The dynamic simulation results from previous models that neglect the operating gear centre distance change and those from the new model that incorporate the operating gear centre distance change were obtained by numerical integration of the differential equations of motion using the Newmark method. Some common diagnostic tools were utilized to investigate the difference and comparison of the fault diagnostic results between the two models. The results of this paper indicate that the major difference between the two diagnostic results for the cracked tooth exists in the extended duration of the crack event and in changes to the phase modulation of the coherent time synchronous averaged signal even though other notable differences from other diagnostic results can also be observed. [ABSTRACT FROM AUTHOR]

Anaerobic sludge from sewage treatment was employed to derive a microbial colony that is capable of anaerobic oxidation of methane coupled with sulfate reduction and denitrification. Investigations revealed that methane can be oxidized with sulfate reduction and denitrification. When sulfate and nitrite acted as electron acceptors together, the rates and amount of methane conversion were higher than that when sulfate or nitrite alone was employed as an electron acceptor. The oxidation rate and amount of methane conversion reached 1.9 mg/(d•gVSS) and 22.24 mg, respectively. Methanotrophic bacteria, such as M. oxyfera , and Methylocystis sp., sulfate-reducing bacteria (SRB), e.g. Desulfosporosinus sp., and Desulfuromonas sp.; and denitrification bacteria, such as Hyphomicrobium sp. , and Diaphorobacter sp., presented in the bacterial community. Anaerobic methanotrophic archaea (ANME), including Methanosaeta sp. and Methanobacterium sp. were found in the archaeal community. These findings indicate the coexistence of ANME, SRB and denitrification bacteria in the system. Nitrite reduction coupled with methane oxidation was performed independently by M. oxyfera during which limited oxygen generated. The oxygen released may be utilized by methanotrophic bacteria to produce organics, which could be used by denitrifying bacteria to reduce nitrite. Methanotrophic archaea could also oxidize methane to carbon dioxide or organics by reverse methanogenesis whereas sulfate was reduced to sulfide by SRB. This study opens possibility for biotechnological process of sulfate reduction and denitrification with methane as electron donor and provides a method for the synergistic treatment of wastewater containing sulfate/nitrite and waste gas containing methane. • Methane was oxidized coupled with sulfate reduction and denitrification. • Sulfate and nitrite as electron co-acceptors for AOM performed better than alone. • Anaerobic digestion sludge could act as the inoculum for AOM. • Methanotrophic bacteria and archaea, denitrifying bacteria and SRB were dominant. • Transfer pathways of AOM, sulfate reduction and denitrification were speculated. [ABSTRACT FROM AUTHOR]

Although permanent bilateral common carotid artery occlusion (2VO) has been demonstrated to induce retinal injury, there is still a lack of systematic research on the complex processing of retinal degeneration. In the present study, time-dependent (at three, 14, 60 days after 2VO surgery) changes of neurotrophic and inflammatory systems, as well as cAMP-responsive element binding protein (CREB) signaling, which has been previously reported to effectively regulate these two systems, were evaluated. First, a morphological study confirmed that 2VO surgery progressively induced severe inner retinal degeneration and down-regulation of synaptic proteins, PSD95 and synaptophysin. The mRNA or protein levels of neurotrophic factors (NGF, BDNF, NT-3 and GDNF) and their receptors (TrkA, TrkB and TrkC) showed marked and persistent down-regulation in the rat retina since three days after 2VO surgery, whereas the gene transcription levels of CNTF were increased and p75NTR mRNA levels remained unchanged. In contrast to inner retinal degeneration, retinal Müller cells displayed rapid and prolonged activation since three days after 2VO lesion, whereas the microglia cell number, and TNF-α and IL-1β levels showed a robust increase with a maximal effect at three days and returned to levels that were slightly over baseline at 14 and 60 days after 2VO lesion. Interestingly, the gene expression levels of iNOS significantly decreased in the rat retina at both three and 14 days after 2VO surgery. Finally, as we hypothesized, remarkable reduction of CREB and extracellular signal-regulated kinase (ERK) phosphorylation levels were observed in the rat retina at three days after 2VO surgery. Thus, for the first time, our study demonstrated that chronic ischemia induced long-term aberrant CREB signaling and time-dependent progressive dysregulation of neurotrophic and inflammatory systems in the retina, which may provide important clues for a better understanding of the pathogenesis of retinal ischemic damage. [ABSTRACT FROM AUTHOR]

Abstract: A fully divergence-free method is proposed for generation of inhomogeneous/anisotropic turbulence with large spatial variation. The method is based on the method of Smirnov et al., which is known to violate the divergence-free constraint when spatial variation of turbulence is present. In the proposed method a vector potential field is introduced; by taking the vector curl of the potential field one can generate a strictly divergence-free flow field. A novel formulation for scaling the vector potential field, together with a coordinate transformation strategy, is proposed in this work. The result is a six-step procedure for the generation of inhomogeneous turbulence fields. The proposed formulation is proven to reproduce the prescribed velocity correlation with energy spectrum at large Reynolds numbers. Four test cases are considered to evaluate the new method. First, the statistical quantities introduced in the proposed method are verified numerically in a classical homogeneous turbulence case. Then, the performance of the new method is demonstrated in three different inhomogeneous turbulence cases: a confined turbulent flow in a “slip-wall” box, a planar channel flow and an annular flow. It is shown that the unphysical patterns in the fluctuation fields and divergence errors produced with Smirnovʼs method are absent in the results from the new method. The accuracy of the proposed methods is verified by comparing the velocity correlations with the prescribed scaling functions. The proposed method is efficient and simple to implement. [Copyright &y& Elsevier]

Abstract: The time-marching approach has clear physical meaning and strict mathematical nature and has been applied in computation of compressible flows widely and extended to many uniform algorithms for All-Speed flows. Remedy for its weakness in the problem of checkerboard decoupling of pressure field for incompressible flows is envisaged with the time-marching momentum interpolation method (MIM) taken into account in this paper. Existing preconditioning methods for suppressing decoupling and time-marching MIM are analyzed for this purpose, and algorithms of time-marching MIM are proposed for steady and unsteady flows and for All-Speed flows. Asymptotic analysis shows that the supposed time-marching MIM has at least a third-order accuracy, better than the existing time-marching coupling methods, which only have an accuracy of the same order as the adopted scheme has. Effects of the time step sizes on the ability of the time-marching MIM to suppress the checkerboard pressure decoupling are particularly discussed in terms of the dual-time stepping approach, and it is revealed how the decreased sizes of either the pseudo- or physical-time step increases the possibility of decoupling and how Choi’s modification, in which the history of the interface velocity is decided by itself instead of the arithmetic average of the velocities on its adjacent nodes, removes the unphysical pressure oscillation with small size of the physical time step but leads to divergence with the pseudo-time step as well. As a remedy for the pseudo-time step, such methods are recommended as implicit methods and the local-time step method with a proposed modification of the time-marching MIM preventing accuracy loss due to very large time step size. Numerical experiments support the theoretical analyses and show the validity of the time-marching MIM proposed. [ABSTRACT FROM AUTHOR]

Abstract: In this study, removal of chromium (VI) from aqueous solution by walnut hull (a local low-cost adsorbent) was studied. The extent of adsorption was investigated as a function of solution pH, contact time, adsorbent and adsorbate concentration, reaction temperature and supporting electrolyte (sodium chloride). The Cr (VI) removal was pH-dependent, reaching a maximum (97.3%) at pH 1.0. The kinetic experimental data were fitted to the first-order, modified Freundlich, intraparticle diffusion and Elovich models and the corresponding parameters were obtained. A 102.78kJ/molEa (activation energy) for the reaction of chromium (VI) adsorption onto walnut indicated that the rate-limiting step in this case might be a chemically controlled process. Both the Langmuir and Freundlich isotherms were suitable for describing the biosorption of chromium (VI) onto walnut hull. The uptake of chromium (VI) per weight of adsorbent increased with increasing initial chromium (VI) concentration up to 240–480mg/L, and decreased sharply with increasing adsorbent concentration ranging from 1.0 to 5.0g/L. An increase in sodium chloride (as supporting electrolyte) concentration was found to induce a negative effect while an increase in temperature was found to give rise to a positive effect on the chromium (VI) adsorption process. Compared to the various other adsorbents reported in the literature, the walnut hull in this study shows very good promise for practical applicability. [Copyright &y& Elsevier]

Abstract: A new scheme, All-Speed-Roe scheme, was proposed for all speed flows. Compared with traditional preconditioned Roe scheme, All-Speed-Roe scheme changes non-linear eigenvalues in the numerical dissipation terms of Roe-type schemes. With an asymptotic analysis, the low Mach number behaviour of the scheme is studied theoretically in two ways. In one way, All-Speed-Roe scheme is regarded as finite magnification of Low-Speed-Roe scheme in the low Mach number limit. In the other way, a general form of All-Speed-Roe scheme is analyzed. Both ways demonstrate that All-Speed-Roe scheme has the same low Mach number behaviour as the original governing equation in the continuous case, which includes three important features: pressure variation scales with the square of the Mach number, the zero order velocity field is subject to a divergence constraint, and the second order pressure satisfies a Poisson-type equation in the case of constant-entropy. The analysis also leads to an unexpected conclusion that the velocity filed computed by traditional preconditioned Roe scheme does not satisfy the divergence constraint as the Mach number vanishes. Moreover, the analysis explains the reason of checkerboard decoupling and shows that momentum interpolation method provides a similar mechanism as traditional preconditioned Roe scheme inherently possesses to suppress checkerboard decoupling. In the end, general rulers for modifying non-linear eigenvalues are obtained. Finally, several numerical experiments are provided to support the theoretical analysis. All-Speed-Roe scheme has a sound foundation and is expected to be widely studied and applied to all speed flow calculations. [Copyright &y& Elsevier]

Abstract: Synthetic oligonucleotides had been employed in DNA repair and promised great potentials in gene therapy. To test the ability of single-stranded oligonucleotide (SSO)-mediated gene repair within a chromosomal site in human cells, a HeLa cell line stably integrated with mutant enhanced green fluorescence protein gene (mEGFP) in the genome was established. Transfection with specific SSOs successfully repaired the mEGFP gene and resulted in the expression of functional fluorescence proteins, which could be detected by fluorescence microscopy and FACS assay. Western blot showed that EGFP was only present in the cells transfected with correction SSOs rather than the control SSOs. Furthermore, DNA sequencing confirmed that phenotype change resulted from the designated nucleotide correction at the target site. Using this reporter system, we determined the optimal structure of SSO by investigating the effect of length, modifications, and polarities of SSOs as well as the positions of the mismatch-forming nucleotide on the efficiency of SSO-mediated gene repair. Interestingly, we found that SSOs with mismatch-forming nucleotide positioned at different positions have varying potencies that homology at the 5′-end of SSOs was more crucial for the SSO’s activity. These results provided guidance for designing effective SSOs as tools for treating monogenic inherited diseases. [Copyright &y& Elsevier]

The present study reports changes in synaptic function and plasticity [long-term potentiation (LTP)] in a recently developed mouse model of Alzheimer''s disease (CRND8 line) harboring a double amyloid precursor protein mutation (APPswe/ind). In 9-week-old preplaque transgenic (Tg) mice brain slices, basal synaptic function in the hippocampal CA1 area was unchanged. Only one of three different LTP induction protocols revealed early influence of genotype on synaptic plasticity. By 20 weeks of age, there were numerous plaques in the hippocampus from Tg mice associated with more robust evidence for genotype-related effects in synaptic function. Field potential maximum slope was consistently decreased and LTP was increased, irrespective of the stimulation protocol used. In addition, there was clear evidence of increased synaptic excitability in Tg mice. Furthermore, the maximum amplitude of evoked IPSCs was decreased whereas the maximum amplitude of evoked EPSCs was increased in 20-week-old Tg mice. Collectively, these results suggest a number of APP genotype-related changes in the fine-tuning of the CA1 area circuitry, some of which are likely to contribute to the pathology-dependent effects on LTP observed in CRND8 mice. [Copyright &y& Elsevier]

Abstract: Tuning surface charge property by a floating gate field effect transistor (FGFET) is proposed and analyzed for the first time. The FGFET has an additional floating gate electrode embedded inside the dielectric channel wall and is superior to the conventional FET to tune the surface charge property of a dielectric material in contact with an aqueous solution. [Copyright &y& Elsevier]

• The planetary gear mathematical model with detailed planet bearing dynamics was developed. • The planet bearing stiffness was calculated by the Hertzian contact theory. • The planet bearing faults were modelled and incorporated into the planetary gear model. • A modified signal processing method were used to enhance the instantaneous angular speed. • The IAS signal was found to be an effective tool for the planet bearing monitoring. This paper aims to investigate the effectiveness of using the torsional vibration signal as a diagnostic tool for planet bearing fault detection. The inner race of the planet bearing is connected to the planet carrier and its outer race is connected to the planet gear bore hole. When moving, the planet bearing not only spins around the planet gear axis, but also revolves about the sun gear axis. This rotating mechanism poses a challenge for the condition monitoring of the planet bearing because of the variant vibration transfer paths. The transducer mounted on the carrier arm measuring the torsional vibration is theoretically free from this modulation effect and it is used in this research to extract the diagnostic information from the torsional vibration. A 34 degrees of freedom planetary gear lumped-parameter model with detailed planet bearing model was developed to obtain the dynamic response. The planet bearing was modelled by 5 degrees of freedom, with 2 degrees of freedom from the outer race, 2 degrees of freedom from the inner race and one degree of freedom from the sprung-mass. The variations of the sun-planet and ring-planet mesh stiffnesses were evaluated by the finite element method and the variation of the planet bearing stiffness was evaluated by the Hertzian contact theory. The localized faults on the planet bearing inner race, outer race and the rolling element were created mathematically and then these faults were incorporated into the planetary gear model to obtain the faulted vibration signal. The linear prediction method and the minimum entropy deconvolution method were used to enhance the planet bearing signal and then the amplitude demodulation results were analysed. It was found that the carrier arm instantaneous angular speed was an effective alternative approach for planet gear condition monitoring. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer is reported a very complex disease along with heterogeneous morphological characteristics and unrelated clinical behavior, and is a leading cancer among female. Nevertheless, chemo-resistance is frequently observed. Adriamycin (ADM) is a always employed drug to treat clinical breast cancer. However, strong resistance to ADM limited its clinical efficacy. Deregulation of HDAC6 activity is linked to various diseases including cancer resulting in accumulating interest for developing HDAC6 inhibitors. In the present study, for the first time, we found that 4-Hydroxybenzoic acid (4-HBA), as histone deacetylase 6 (HDAC6) inhibitor, could successfully reverse ADM resistance in human breast cancer cells. 4-HBA significantly promoted the anticancer effect of ADM on apoptosis induction, as evidenced by the increased expressions of Caspase-3 and PARP cleavage, which was associated with the promotion p53 and homeodomain interacting protein kinase-2 (HIPK2) expressions in ADM-resistant breast cancer cells. Furthermore, the suppressive effect of ADM on drug-resistant breast cancer cells was accelerated by 4-HBA through increasing the number of cells distributed in G2/M phase of cell cycle arrest. Inhibiting HIPK2/p53 pathway could abolish 4-HBA/ADM co-treatment-induced apoptosis and G2/M cell cycle arrest. Importantly, HDAC6 expressions were also significantly down-regulated in ADM-resistance breast cancer cells co-treated with ADM and 4-HBA. Additionally, 4-HBA clearly potentiated the anticancer role of ADM in the MCF-7 breast cancer animal model with low toxicity. Therefore, 4-HBA could be applied as an effective HDAC6 inhibitor to reverse human breast cancer resistance. Herein, the 4-HBA and ADM combination might represent as a useful therapeutic strategy to prevent human breast cancer. Highlights • 4-Hydroxybenzoic acid enhances the sensitivity of MCF-7/ADM to ADM-induced apoptosis. • 4-Hydroxybenzoic acid induces apoptosis in breast cancer cell lines. • 4-Hydroxybenzoic acid induces cell cycle arrest in G2/M phase. [ABSTRACT FROM AUTHOR]

Social well-being reflects the appraisal of one's circumstance and functioning in society, which is crucial for individuals' mental and physical health. However, little is known about the neural processes associated with social well-being. In this study, we used voxel-based morphometry (VBM) to identify the brain regions underlying individual differences in social well-being, as measured by the Social Well-being Scale (SWBS), in a large sample of young healthy adults. We found that social well-being was negatively correlated with gray matter volume in left mid-dorsolateral prefrontal cortex (mid-DLPFC) that is implicated in executive functioning, emotional regulation and social reasoning. The results remained significant even after controlling for the effect of socioeconomic status. Furthermore, although basic personality factors such as neuroticism, extraversion, and conscientiousness (as measured by the NEO Personality Inventory) all contributed to social well-being, only extraversion acted as a mediational mechanism underlying the association between the left mid-DLPFC volume and social well-being. Together, our findings provide the first evidence for the structural basis of individual differences in social well-being, and suggest that the personality trait of extraversion might play an important role in the acquisition and process of social well-being. [ABSTRACT FROM AUTHOR]

Abstract: We present an improved numerical scheme for numerical simulations of low Mach number turbulent reacting flows with detailed chemistry and transport. The method is based on a semi-implicit operator-splitting scheme with a stiff solver for integration of the chemical kinetic rates, developed by Knio et al. [O.M. Knio, H.N. Najm, P.S. Wyckoff, A semi-implicit numerical scheme for reacting flow II. Stiff, operator-split formulation, Journal of Computational Physics 154 (2) (1999) 428–467]. Using the material derivative form of continuity equation, we enhance the scheme to allow for large density ratio in the flow field. The scheme is developed for direct numerical simulation of turbulent reacting flow by employing high-order discretization for the spatial terms. The accuracy of the scheme in space and time is verified by examining the grid/time-step dependency on one-dimensional benchmark cases: a freely propagating premixed flame in an open environment and in an enclosure related to spark-ignition engines. The scheme is then examined in simulations of a two-dimensional laminar flame/vortex-pair interaction. Furthermore, we apply the scheme to direct numerical simulation of a homogeneous charge compression ignition (HCCI) process in an enclosure studied previously in the literature. Satisfactory agreement is found in terms of the overall ignition behavior, local reaction zone structures and statistical quantities. Finally, the scheme is used to study the development of intrinsic flame instabilities in a lean H2/air premixed flame, where it is shown that the spatial and temporary accuracies of numerical schemes can have great impact on the prediction of the sensitive nonlinear evolution process of flame instability. [Copyright &y& Elsevier]

Abstract: Targeted gene repair mediated by single-stranded DNA oligonucleotides (SSOs) is a promising method to correct the mutant gene precisely in prokaryotic and eukaryotic systems. We used a HeLa cell line, which was stably integrated with mutant enhanced green fluorescence protein gene (mEGFP) in the genome, to test the efficiency of SSO-mediated gene repair. We found that the mEGFP gene was successfully repaired by specific SSOs, but the efficiency was only ∼0.1%. Then we synthesized a series of nonspecific oligonucleotides, which were single-stranded DNA with different lengths and no significant similarity with the SSOs. We found the efficiency of SSO-mediated gene repair was increased by 6-fold in nonspecific oligonucleotides-treated cells. And this improvement in repair frequency correlated with the doses of the nonspecific oligonucleotides, instead of the lengths. Our evidence suggested that this increased repair efficiency was achieved by the transient alterations of the cellular proteome. We also found the obvious strand bias that antisense SSOs were much more effective than sense SSOs in the repair experiments with nonspecific oligonucleotides. These results provide a fresh clue into the mechanism of SSO-mediated targeted gene repair in mammalian cells. [Copyright &y& Elsevier]

Abstract: Tumour necrosis factor (TNF) family ligands and their corresponding receptors play important roles in the immune system and are involved in immune regulation such as lymphoid development, cell proliferation, differentiation, activation and death. Antibodies against these ligands and receptors together with Fc-fusion proteins, have been particularly useful as immunological tools in addressing the underlying involvement of these proteins in these contexts and furthermore, have given us hope in using them as potential therapeutic agents. Over last few years, there have been many additions to these ever-growing TNF family ligands and their receptors. Here, we have generated and characterised a set of monoclonal antibodies, together with mAbs from the HLDA workshop, against DcR1, DcR2, DR4, DR5, TRAIL, APRIL, BAFF, BAFF-R, BCMA, and TACI, which may be useful in phenotypic and functional studies of the role of TNF and TNF receptor family in immune function and regulation in relation to health and disease. [Copyright &y& Elsevier]

The chain length (CL) of fatty acids (FAs) is pivotal to oil property, yet to what extent it can be customized in industrial oleaginous microalgae is unknown. In Nannochloropsis oceanica , to modulate long-chain FAs (LCFAs), we first discovered a fungi/bacteria-originated polyketide synthase (PKS) system which involves a cytoplasmic acyl-ACP thioesterase (NoTE1). NoTE1 hydrolyzes C16:0-, C16:1- and C18:1-ACP in vitro and thus intercepts the specific acyl-ACPs elongated by PKS for polyunsaturated FA biosynthesis, resulting in elevation of C16/C18 monounsaturated FAs when overproduced and increase of C20 when knocked out. For medium-chain FAs (MCFAs; C8-C14), C8:0 and C10:0 FAs are boosted by introducing a Cuphea palustris acyl-ACP TE (CpTE), whereas C12:0 elevated by rationally engineering CpTE enzyme's substrate-binding pocket to shift its CL preference towards C12:0. A mechanistic model exploiting both native and engineered PKS and type II FAS pathways was thus proposed for manipulation of carbon distribution among FAs of various CL. The ability to tailor FA profile at the unit CL resolution from C8 to C20 in Nannochloropsis spp. lays the foundation for scalable production of designer lipids via industrial oleaginous microalgae. • Broad-spectrum carbon chain length modulation of fatty acids in microalgae. • Rational engineering thioesterase to shift substrate preference in carbon chain length. • A new model for fatty-acid chain length control in industrial microalgae. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a fatal and intractable disease accompanied by the comorbidity of chronic neuropathic pain. Here, we purposed to explore the therapeutic effect and the underlying mechanism of Resolvin D2 (RvD2) on neuropathic pain after SCI. The in vivo model of traumatic SCI rats was established. Primary microglia isolated from neonatal rats were induced by TNF-α in vitro. The locomotor ability was assessed by the Basso-Beattie-Besnahan score. Hargreaves methods and Von Frey fibrofilaments were used to evaluate the symptoms of neuropathic pain including allodynia and hyperalgesia in rats. The cytotoxicity of RvD2 was evaluated by MTT assay. ELISA kit was applied to access the levels of inflammatory factors. And the expression levels of related mRNA and proteins were determined by qRT-PCR, western blotting and immunofluorescence staining. The targeting relationship between miR-155 and PTEN was verified by dual-luciferase reporter (DLR) assay. We found that RvD2 mitigated locomotor dysfunction, allodynia and hyperalgesia of SCI rats. In addition, RvD2 treatment suppressed pro-inflammatory phenotype but promoted anti-inflammatory differentiation in microglia. Furthermore, RvD2 treatment inhibited the upregulated expression level of miR-155 which was caused by NF-κB activation and then recovered the autophagy flux via targeting PTEN, thereby relieving the inflammatory response in the TNF-α-induced primary microglia. In summary, RvD2 treatment could recover the autophagy flux via suppressing NF-κB-modulated miR-155 expression to activate anti-inflammatory microglia and then inhibit the inflammatory response and even mitigate neuropathic pain following SCI. • RvD2 could alleviate neuropathic pain evoked by spinal cord injury in rats. • RvD2 inhibited microglia M1 polarization-mediated neuroinflammation. • RvD2 restored the impaired autophagic flux via modulating miR-155/PTEN axis. • RvD2 may promote autophagy through AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

The RNA-binding protein fused in sarcoma (FUS) forms physiological granules and pathological fibrils, which facilitate RNA functions and cause neurodegenerative diseases, respectively. Phosphorylation at Ser/Thr residues may regulate the functional assembly of FUS and prevent pathological aggregation in cells. However, the low-complexity nature of the FUS sequence makes it challenging to characterize how phosphorylation of specific sites within the core amyloid-forming segment affects aggregation. Taking advantage of the recently solved molecular structures of the fibrillar core of the FUS low-complexity (FUS-LC) domain, we systematically investigated the aggregation of repeated segments within the core. We identified a segment with a strong amyloid-forming tendency that induced the aggregation of FUS-LC domain in phase-separated liquid droplets and further seeded the aggregation of full-length FUS. The aggregation propensity and seeding ability of this amyloid-forming segment were modulated by site-specific phosphorylation. Solid-state nuclear magnetic resonance (NMR) spectroscopy and computational modeling implied that site-specific phosphorylation at Ser61 plays key roles in FUS assembly by disrupting both intra- and intermolecular interactions that maintain the amyloid core structure. Image 1 • A segment with strong tendency to form amyloid fibrils of FUS was explored. • The segment can convert phase separated droplets to pathological fibrils. • Phosphorylation at Ser61 could inhibit the aggregation of the segment. • Phos-Ser61 could prohibit the seeding effects due to its retarded fibril formation process. • Phos-Ser61 disrupts both intra- and intermolecular interactions of the segment. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis after myocardial infarction (MI) is mainly associated with cardiac fibroblasts and its differentiation is the key pathological process. However, the cellular mechanism of fibroblast-to-myofibroblast conversion has not been clarified and a deeper mechanistic understanding is needed. We found that miR-574–5p was up-regulated in TGF-β-induced myofibroblast differentiation. Silencing transiently miR-574–5p in HCFs, we found that suppression of miR-574–5p decreased myofibroblasts differentiation as validated by expression levels of fibrosis related genes, EDU imaging assay, wound healing assay and transwell assays. Conversely, overexpression of miR-574–5p displayed opposite results. ARID3A was verified as a direct target gene of miR-574–5p and decreased level of ARID3A forced fibroblast-to-myofibroblast differentiation of TGF-β-induced HCFs. Our data suggests that miR-574–5p plays a pivotal role in human cardiac fibroblasts (HCFs) myofibroblast differentiation and demonstrates that miR-574–5p and arid3a may be a novel therapeutic target for cardiac fibrosis. • We first demonstrated that miR-574–5p promotes the differentiation of HCFs. • ARID3A is the direct target gene of miR-574–5p. • Suppression of ARID3A recovered the anti-fibrotic response of miR-574–5p knockdown on TGF-β stimulation. [ABSTRACT FROM AUTHOR]

Visible light-driven photocatalytic aerobic oxidative coupling processes of amines have been successfully performed in the presence of a flower-like Bi 2 O 2 CO 3 catalyst. • Visible light-driven of benzyl amine is successfully performed. • The flower-like Bi 2 O 2 CO 3 is a preferable catalyst in the presence of O 2. • A 99% yield of N-benzylidenebenzylamine is obtained at room temperature. • The catalyst still keeps a high activity after being recycled for 5 times. The photocatalytic selective transformation of amines is a green and cost-effective technology to obtain value-added products in chemical industry. In this work, a series of bismuth-based photocatalysts including Bi 2 MoO 6 , Bi 2 WO 6 , Bi 5 O 7 Cl, Bi 5 O 7 Br, Bi 5 O 7 I, BiPO 4 , BiVO 4 , Bi 2 O 3 and various morphology Bi 2 O 2 CO 3 (flower-like, sponge-like, plate-like and spherical) were synthesized and employed in the aerobic oxidative coupling of benzylamine. It is found that flower-like Bi 2 O 2 CO 3 exhibited the highest photocatalytic activity, in which a 100% conversion of benzylamine with 99.0% selectivity of N -benzylidenebenzylamine was obtained at room temperature. Moreover, the photocatalytic oxidative coupling processes of various aromatic and aliphatic amines were further investigated, and excellent yields and selectivities of corresponding products are attained. Then, based on characterization results (XRD, SEM, BET and XPS, etc.) of catalyst, high photocatalytic activity of flower-like Bi 2 O 2 CO 3 is attributed to thin nanopetals, low band gap, the morphology and large specific surface area. Finally, a possible reaction mechanism is proposed for the photocatalytic oxidative coupling of benzyl amine. [ABSTRACT FROM AUTHOR]

Denitrifying anaerobic methane-oxidizing (DAMO) processes, which link anaerobic methane oxidation (AMO) and denitrification, have a promising prospect in anaerobic wastewater treatment. In bioelectrochemical systems (BES), DAMO consortium presented potent metabolic activity. However, the extracellular electron transfer (EET) in BES was poorly understood. This study investigated the EET mechanisms and modes of electron transport in BES dominated by anaerobic methanotrophic bacteria. In the bioreactors with the auxiliary voltage of 0.5 and 1.1 V, named EMN-0.5 and EMN-1.1, respectively, biological voltages of 0.198 and 0.329 V were generated with power densities of 0.6 and 1.20 mW/m2, after removing the voltage. High throughput and metagenome analyses demonstrated that main methanotrophs were DAMO bacteria and Methylocystis sp. The electroactive bacteria detected were Pseudomonas sp., Hypomicrobium sp., Thiobacillus sp, and Rhodococcus sp. The pil , cytochrome c , hdr , and he / fp genes related to EET were present on the electrode surfaces. Carbon 13 isotope tracing and chemicals analysis by GC-MS exhibited that methanol was an intermediate product released to extracellular environment and acted as the electronic carrier to drive the EET in methane oxidation. Extracellular electron transfer was achieved through the collaboration of DAMO bacteria, Methylocystis sp., and Pseudomonas sp. Anthraquinone 2-sulfonic acid ester (AQS) could improve the rate of electron transfer to the extracellular space, especially in the EMN-0.5 reaction system. This study provides a new understanding of AMO consortium metabolism in BES and may provide a scientific basis for developing methane control technology. [Display omitted] • 1.20 mW/m2 was generated in the bioelectrochemical systems driven DAMO bacteria. • Electroactive bacteria and EET genes were identified on the surface of electrodes. • Methanol was likely the electron carrier of methanotrophs and electroactive bacteria. • AQS, as an electron shuttle, enhanced the EET process in the system of EMN-0.5. • DAMO bacteria, Methylocystis sp. and Pseudomonas sp. might jointly complete EET. [ABSTRACT FROM AUTHOR]

4-Carboxyphenoxybutanoic acid (H 2 cpob) and its monosodium salt (NaHcpob) are synthesized and characterized. The crystal structure of NaHcpob shows that the sodium atoms are connected by the carboxyl group of Hcpob−, forming a three-dimensional coordination polymer network. NaHcpob reacts with metal salts and N -containing ligands produced following complexes: [Co(cpob)(H 2 O) 2 ] n 1 , [Zn(cpob)(phen)(H 2 O)] 2 2 , [Cd(cpob)(phen)] n 3 , [Mn(cpob)(phen)·4H 2 O] n 4 , and [Cd 2 (cpob) 2 (bimb)] n 5 (phen ​= ​1,10-phenanthroline, bimb ​= ​1,4-bis(imidazole-1-ylmethyl)benzene). Single-crystal X-ray diffraction analysis showed that these complexes have different metal-organic frameworks, ranging from binuclear (2) to one-dimensional (3 and 4), two-dimensional (1), and three-dimensional (5) arrangements. When only H 2 cpob forms a complex with metal ions, the ligand connects the metal ions into a higher-dimensional structure. In contrast, the terminal ligand (phen) added as an auxiliary ligand forms a low-dimensional complex. And when the bridging auxiliary ligand (bimb) is added, the high-dimensional complex can still be formed. The flexible conformation of H 2 cpob and the different N -containing ligands may be responsible for the structural diversity of binary H 2 cpob metal complexes. These metal complexes also displayed many differences in their fluorescence properties in the solid state. NaHcpob reacts with M(II) salts and N -containing ligands produced five complexes. Single-crystal X-ray diffraction analysis showed that these complexes have different metal-organic frameworks, ranging from binuclear to one-dimensional, two-dimensional, and three-dimensional arrangements. [Display omitted] • H 2 cpob and its monosodium salt (NaHcpob) have been synthesized. • Five M(II) complexes are constructed from NaHcpob and N -donor ligands. • These complexes have different metal-organic frameworks. • Luminescence properties and lifetime of solid state are documented. [ABSTRACT FROM AUTHOR]

Background Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear. Objective The aim of this study was to investigate the effect and mechanism of HMGA2 in inducing invasion and migration in NPC. Methods In NPC tissues samples, the association of HMGA2 mRNA expression with clinicopathological characteristics were estimated by real-time quantitative RT-PCR(qRT-PCR). In vitro, following the silencing of HMGA2 in CNE-1 and CNE-2 cell lines, the viability and metastatic ability were analyzed using Cell Counting Kit-8 (CCK8), colony formation assay, and transwell assay. EMT and transforming growth factor-beta (TGFβ)/Smad3 signaling pathway-related protein expression changes were evaluated using western blot. Results HMGA2 was upregulated in NPC cell lines and clinical specimens ( P < 0.01), and HMGA2 expression correlated significantly with metastasis ( P = 0.02) and disease-free survival of NPC (hazard ratio: 3.52; 95% confidence interval: 1.34–7.79; P = 0.01). In addition, following in vitro knockdown of HMGA2, the aggressiveness of cells was markedly inhibited, Vimentin and Snail level was downregulated and E-cadherin expression was upregulated. Moreover, the expression of key proteins TGFβRII and p-Smad3 of the TGFβ/Smad3 signaling pathway was inhibited by the downregulation of HMGA2. Conclusion HMGA2 might maintain EMT-induced invasion and migration through the TGFβ/Smad3 signaling pathway in NPC cell lines. [ABSTRACT FROM AUTHOR]

Malonyl-coenzyme A: acyl-carrier protein transacylase (MCAT) catalyzes the transfer of malonyl group from malonyl-CoA to the holo-acyl carrier protein (Holo-ACP), yielding malonyl-ACP. The overall reaction has been extensively studied in heterotrophic microorganisms, while its mechanism in photosynthetic autotrophs as well as the stepwise reaction information remains unclear. Here the 2.42 Å crystal structure of MCAT from photosynthetic microorganism Synechocystis sp. PCC 6803 is presented. It demonstrates that Arg113, Ser88 and His188 constitute catalytic triad. The second step involved ACP-MCAT-malonyl intermediate is speed-limited instead of the malonyl-CoA-MCAT intermediate in the first step. Therefore His87, Arg113 and Ser88 render different contributions for the two intermediates. Additionally, S88T mutant initializes the reaction by H87 deprotonating S88T which is different from the wild type. [ABSTRACT FROM AUTHOR]

Defect in mitochondrial biogenesis and cardiac energy metabolism is a critical contributing factor to cardiac hypertrophy and heart failure. Sentrin/SUMO specific protease 1 (SENP1) mediated regulation of PGC-1α transcriptional activity plays an essential role in mitochondrial biogenesis and mitochondrial function. However, whether SENP1 plays a role in cardiac hypertrophy and failure is unknown. We investigated whether alteration in SENP1 expression affects cardiomyopathy and the underlying mechanism. In our present study, we found that the expression of SENP1 was induced in mouse and human failing hearts associated with induced expression of mitochondrial genes. SENP1 expression in cardiomyocytes was induced by hypertrophic stimuli through calcium/calcineurin-NFAT3. SENP1 regulated mitochondrial gene expression by de-SUMOylation of MEF-2C, which enhanced MEF-2C-mediated PGC-1α transcription. Genetic induction of SENP1 led to mitochondrial dysregulation and cardiac dysfunction in vivo. Our data showed that pathogenesis of cardiomyopathy is attributed by SENP1 mediated regulation of mitochondrial abnormities. SENP1 up-regulation in diseased heart is mediated via calcineurin-NFAT/MEF2C-PGC-1α pathway. [ABSTRACT FROM AUTHOR]

The no-reflow phenomenon induced by ischemia-reperfusion (I/R) injury seriously limits the therapeutic value of coronary recanalization and leads to a poor prognosis. Previous studies have shown that luteolin (LUT) is a vasoprotective factor. However, whether LUT can be used to prevent the no-reflow phenomenon remains unknown. Positron emission tomography perfusion imaging, performed to detect the effects of LUT on the no-reflow phenomenon in vivo, revealed that LUT treatment was able to reduce the no-reflow area in rat I/R models. In vitro, LUT was shown to reduce the hypoxia-reoxygenation injury-induced endothelial permeability and apoptosis. The levels of malondialdehyde, reactive oxygen species and NADPH were also measured and the results indicated that LUT could inhibit the oxidative stress. Western blot analysis revealed that LUT protected endothelial cells from I/R injury by regulating the Wnt/β-catenin pathway. Overall, we concluded that the use of LUT to minimize I/R induced microvascular damage is a feasible strategy to prevent the no-reflow phenomenon. • Luteolin serves as a potential candidate for the prevention of the no-reflow. • Luteolin can minimize I/R induced microvascular damage. • Luteolin alleviates ischemia/reperfusion injury via regulating Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Abstract: The Escherichia coli gene cluster ymgABC was identified in transcriptome studies to have a role in biofilm development and stability. In this study, we showed that YmgB represses biofilm formation in rich medium containing glucose, decreases cellular motility, and protects the cell from acid indicating that YmgB has a major role in acid-resistance in E. coli. Our data show that these phenotypes are potentially mediated through interactions with the important cell signal indole. In addition, gel mobility-shift assays suggest that YmgB may be a non-specific DNA-binding protein. Using nickel-enrichment DNA microarrays, we showed that YmgB binds, either directly or indirectly, via a probable ligand, genes important for biofilm formation. To advance our understanding of the function of YmgB, we used X-ray crystallography to solve the structure of the protein to 1.8 Å resolution. YmgB is a biological dimer that is structurally homologous to the E. coli gene regulatory protein Hha, despite having only 5% sequence identity. This supports our DNA microarray data showing that YmgB is a gene regulatory protein. Therefore, this protein, which clearly has a critical role in acid-resistance in E. coli, has been renamed as AriR for regulator of acid resistance influenced by indole. [Copyright &y& Elsevier]

Abstract: The ideal gene-therapy vector for treating genetic disorders should deliver intact therapeutic genes and their essential regulatory elements into the specific “safe genomic site” and realize long-term, self-regulatory expression. For β-thalassemia gene therapy, viral vectors have been broadly used, but the accompanying insertional mutation and immunogenicity remain problematic. Hence, we aimed to develop new non-viral vectors that are efficient and safe in treating diseases. As previous studies have demonstrated that physiological expression of β-globin genes requires both a 5′ locus control region and 3′ specific elements, we constructed a new human chromosome-derived targeting vector to transfer the intact β-globin gene cluster into K562 cells. The whole β-globin gene cluster was precisely integrated into the target site and expressed in a self-regulatory pattern. The results proved that the human chromosome-derived vector was specifically targeted to the human genome and this could provide a novel platform for further gene therapy research. [Copyright &y& Elsevier]

Abstract: The expression of the apoptosis-inducing ligands, TNF-α, FasL and TRAIL on peripheral blood mononuclear cells (PBMC) and the levels of their soluble form (TNF-α, sFasL and sTRAIL) in plasma from 40 hemorrhagic fever with renal syndrome (HFRS) patients as well as 26 healthy blood donors were determined by flow cytometry (FCM) analysis and sandwich ELISA, respectively. The status of Th1, Th2, Tc1 and Tc2 subsets in PBMC was evaluated by intracellular cytokine staining and FCM. Compared to controls, the expression of membrane bound FasL and TRAIL was up-regulated on surface of PBMC isolated from the HFRS patients, particularly on CD8+ T lymphocytes. The levels of TNF-α, sFasL and sTRAIL in plasma from the HFRS patients in the acute phase increase 4.7-fold, 6.0-fold and 1.8-fold, respectively, over those from the healthy donors. The percentage of Th1, Tc1 and Tc2 subsets in PBMC from the patients also increased significantly compared with those from healthy donors. These results indicate that dynamic changes occurred in both the membrane bound and soluble forms of apoptosis-inducing ligands (FasL, TRAIL and TNF-α) and proportions of Th1 and CTL in HFRS patients increased. Both factors may play an important role in the etiology of Hantaan virus infection in humans. [Copyright &y& Elsevier]

Abstract: Despite of our knowledge of genetic make up of schistosomes, a number of genes have not been characterized largely due to lack of effective transformation protocols. Here we present electroporation as a strategy for effective introduction of plasmids DNA into schistosomula and adults. Using plasmids of pEGFP-C1 as an expression vector, we first verified that the CMV promoter could direct EGFP to express in primary culture cells from Schistosoma japonicum. Subsequently, the plasmids were introduced into schistosomula and adults by electroporation and EGFP expression was demonstrated using molecular and microscopical methods. Our findings indicate that electroporation is an effective method for transformation of S. japonicum. [Copyright &y& Elsevier]

The RNA splicing endonuclease is responsible for recognition and excision of nuclear tRNA and all archaeal introns. Despite the conserved RNA cleavage chemistry and a similar enzyme assembly, currently known splicing endonuclease families have limited RNA specificity. Different from previously characterized splicing endonucleases in Archaea, the splicing endonuclease from archaeum Sulfolobus solfataricus was found to contain two different subunits and accept a broader range of substrates. Here, we report a crystal structure of the catalytic subunit of the S.solfataricus endonuclease at 3.1Å resolution. The structure, together with analytical ultracentrifugation analysis, identifies the catalytic subunit as an inactive but stable homodimer, thus suggesting the possibility of two modes of functional assembly for the active enzyme. [Copyright &y& Elsevier]