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Globally, most high-grade ores have already been exploited. Contemporary mining tends to focus on the extraction of lower-grade ores thereby leaving large stored tailings open to the environment. As a result, current mines have emerged as hotspots for the migration of metal(loid)s and resistance genes, thereby potentially contributing to a looming public health crisis. Therefore, the management and remediation of tailings are the most challenging issues in environmental ecology. Bioremediation, a cost-effective solution for the treatment of multi-element mixed pollution (co-contamination), shows promise for the restoration of mine tailings. This review focuses on the bioremediation technologies developed to untangle the issues of non-ferrous metal mine tailings. These technologies address the environmental risks of multi-element exposure to the ecosystem and human health risks. It provides a review and comparison of current bioremediation technologies used to mineralize metal(loid)s. The role of plant-microorganisms and their mechanisms in the remediation of tailings are also discussed. The importance of "treating waste with wastes" is crucial for advancing bioremediation technologies. This approach underscores the potential for waste materials to contribute to environmental cleanup processes. The concept of a circular economy is pertinent in this context, emphasizing recycling and reuse. There's an immediate need for international collaboration. Collaboration is needed in policy-making, funding, and data accessibility. Sharing data is essential for the growth of bioremediation globally. [Display omitted] • Co-contamination of tailings has caused catastrophic impacts on the ecological environment. • Mechanisms and field applications of remediation technologies are discussed. • Specialized methods for environmental risk assessment targeted at tailings are needed. • Bioremediation requires oversight to manage risks in challenging tailings. • Combined bioremediation technology coupled with wastes holds great potential for application. [ABSTRACT FROM AUTHOR]

[Display omitted] The development of the effective diagnostic method for the determination of cancer biomarkers is one of the most promising strategies for early clinical diagnosis of cancer. Here, based on the preparation of heterogeneous cuprous oxide coated silver (Ag@Cu 2 O) nanocomposites/graphitic carbon nitride (g-C 3 N 4)/cadmium sulfide (CdS) nanoarrays structure, a highly sensitive photoelectrochemical (PEC) biosensor for the examination of carcinoembryonic antigen (CEA) has been constructed successfully. The combination of photoactive semiconductor materials g-C 3 N 4 and CdS increases the electron transfer rate between them and enhances their photocurrent response, thus greatly increasing the concentration detection range. At the same time, the specific recognition between antigen and antibody is used to form a sandwich structure secondary antibody (Ab 2)/CEA/antibody (Ab 1). And because Ag@Cu 2 O has the function of absorbing light and consuming electron donor. Therefore, the successful measurement of CEA was achieved by labeling Ag@Cu 2 O on Ab 2 and finally immobilizing it on the sensor to correlate the current reduction with the CEA concentration. The sandwich PEC biosensor proposed by this signal amplification strategy under optimal conditions has good analytical performance for CEA, with a wide linear detection range (from 10-5 to 1 ng/mL) and a low detection limit of 0.0011 pg/mL. The PEC biosensor constructed by this method showed high sensitivity, excellent anti-interference ability, favourable repeatability, and good stability. [ABSTRACT FROM AUTHOR]

Acid mine drainage (AMD) caused environmental risks from heavy metal pollution, requiring treatment methods such as chemical precipitation and biological treatment. Monitoring and adapting treatment processes was crucial for success, but cost-effective pollution monitoring methods were lacking. Using bioindicators measured through 16S rRNA was a promising method to assess environmental pollution. This study evaluated the effects of AMD on ecological health using the ecological risk index (RI) and the Risk Assessment Code (RAC) indices. Additionally, we also examined how acidic metal stress affected the diversity of bacteria and fungi, as well as their networks. Bioindicators were identified using linear discriminant analysis effect size (LEfSe), Partial least squares regression (PLS-R), and Spearman analyses. The study found that Cd, Cu, Pb, and As pose potential ecological risks in that order. Fungal diversity decreased by 44.88% in AMD-affected areas, more than the 33.61% decrease in bacterial diversity. Microbial diversity was positively correlated with pH (r = 0.88, p = 0.04) and negatively correlated with bioavailable metal concentrations (r = −0.59, p = 0.05). Similarly, microbial diversity was negatively correlated with bioavailable metal concentrations (bio_Cu, bio_Pb, bio_Cd) (r = 0.79, p = 0.03). Acidiferrobacter and Thermoplasmataceae were prevalent in acidic metal environments, while Puia and Chitinophagaceae were identified as biomarker species in the control area (LDA>4). Acidiferrobacter and Thermoplasmataceae were found to be pH-tolerant bioindicators with high reliability (r = 1, P < 0.05, BW > 0.1) through PLS-R and Spearman analysis. Conversely, Puia and Chitinophagaceae were pH-sensitive bioindicators, while Teratosphaeriaceae was a potential bioindicator for Cu–Zn–Cd metal pollution. This study identified bioindicator species for acid and metal pollution in AMD habitats. This study outlined the focus of biological monitoring in AMD acidic stress environments, including extreme pH, heavy metal pollutants, and indicator species. It also provided essential information for heavy metal bioremediation, such as the role of omics and the effects of organic matter on metal bioavailability. [Display omitted] • The order of ecological risk for sources of AMD pollution had been determined to be Cd > Cu > Pb > As. • Three acid indicator species and one bioindicator species for heavy metals were screened. • A tool was provided to assess soil metal contamination and a screening model for bioindicators. [ABSTRACT FROM AUTHOR]

The quality of soil containing heavy metals (HMs) around nonferrous metal mining areas is often not favorable for plant growth. Three types of plant growth promoting rhizobacteria (PGPR)-assisted ryegrass were examined here to treat Cd, Pb, and Zn contaminated soil collected from a nonferrous metal smelting facility. The effects of PGPR-assisted plants on soil quality, plant growth, and the migration and transformation of HMs were evaluated. Results showed that inter-root inoculation of PGPR to ryegrass increased soil redox potential, urease, sucrase and acid phosphatase activities, microbial calorimetry, and bioavailable P, Si, and K content. Inoculation with PGPR also increased aboveground parts and root length, P, Si, and K contents, and antioxidant enzyme activities. The most significant effect was that the simultaneous inoculation of all three PGPRs increased the ryegrass extraction (%) of Cd (59.04–79.02), Pb (105.56–157.13), and Zn (27.71–40.79), compared to CK control (without fungi). Correspondingly, the inter-root soil contents (%) of total Cd (39.94–57.52), Pb (37.59–42.17), and Zn (34.05–37.28) were decreased compared to the CK1 control (without fungi and plants), whereas their bioavailability was increased. Results suggest that PGPR can improve soil quality in mining areas, promote plant growth, transform the fraction of HMs in soil, and increase the extraction of Cd, Pb, and Zn by ryegrass. PGPR is a promising microbe-assisted phytoremediation strategy that can promote the re-greening of vegetation in the mining area while remediating HMs pollution. [Display omitted] • Plant growth promoting rhizobacteria (PGPR) improves soil quality and plant growth. • PGPR increases the extraction of Cd, Pb and Zn by ryegrass. • PGPR works synergistically. [ABSTRACT FROM AUTHOR]

This study investigated the stability of vibration in a nonlinear suspension system with slow-varying sprung mass under dual-excitation. A mathematical model of the system was first established and then solved using the multi-scale method. Finally, the amplitude-frequency curve of vehicle vibration, the solution's stable region and time-domain curve in Hopf bifurcation were derived. The obtained results revealed that an increase in the lower excitation would reduce the system's stability while an increase in the upper excitation can make the system more stable. The slow-varying sprung mass will change the system's damping from negative to positive, leading to the appearance of limit cycle and Hopf bifurcation. As a result, the vehicle's vibration state is forced to change. The stability of this system is extremely fragile under the effect of dynamic Hopf bifurcation as well as static bifurcation. [ABSTRACT FROM AUTHOR]

Nanostructure Mn 3 O 4 is a promising pseudocapacitive electrode material due to its low cost, environmental compatibility, and intrinsically high capacity. However, the poor electrical conductivity and low accessible active sites limit its performance. We report that one-dimensional (1D) nanoscale Mn 3 O 4 has been coupled with reduced graphene oxide (RGO) to fabricate RGO/Mn 3 O 4 nanohybrid (MORGO) as a pseudocapacitive electrode material with high capacitance. The selective reduction of graphene oxide (GO) in Mn 3 O 4 /graphene oxide (MOGO) to reduced graphene oxide (RGO) while sustaining the unchanged oxidation state of manganese is the key to obtain MORGO. Specific surface area of MORGO is 14 times higher than pure Mn 3 O 4 , and the charge transfer resistance decreases 3.2 times. These enhanced properties lead to excellent specific capacitance of 538 F g −1 at the current density of 0.1 A g −1 , and of 472 F g −1 at 10 A g −1 in 1 M Na 2 SO 4 aqueous electrolyte. The capacitance retained 89% after 2000 cycles, demonstrating its excellent long-term cycling stability. [ABSTRACT FROM AUTHOR]

A series of goethite-modified montmorillonite (GMt) materials was synthesized for the amelioration of cationic cadmium (Cd) and anionic arsenic (As) complex contaminants in soil and water bodies. The results showed that goethite (Gt) was successfully loaded onto the surface of montmorillonite (Mt), which possessed more functional groups (such as Fe–O, and Fe–OH) and a larger specific surface area. GMt-0.5 (Mt loaded with Gt at a ratio of 0.5:1) showed the highest adsorption capacity for Cd(II) and As(III) with the maximum of 50.61 mg/g and 57.58 mg/g, respectively. The removal rate of Cd(II) was highly pH dependent, while the removal rate of As(III) showed little dependence on pH. The goethite on montmorillonite might contribute to the formation of surface complexes with As(III) and oxidation of As(III) to As(V). In the binary system, both, synergistic and competitive adsorption existed simultaneously. Importantly, in the binary system, the removal of As(III) was more favorable because of the electrostatic interaction, formation of a ternary complex, and co-precipitation. In addition, the amendment of GMt-0.5 significantly reduced the availability of Cd and As in the soil. This study suggests that GMt-0.5 is a promising candidate for the simultaneous immobilization of metal (loid)s in both, aqueous solution and mine soil. [Display omitted] • GMt-0.5 has a great removal efficiency for Cd(II) and As(III). • Higher adsorption capacity of GMt-0.5 for As(III) in both two systems. • In the binary system, Cd(II) remarkably enhanced the removal of As(III) by GMt-0.5. • Cd(II) induces As(III) to form ternary complexes and enhances As(III) adsorption. • GMt-0.5 effectively immobilizes Cd and As in mine soil. [ABSTRACT FROM AUTHOR]

The phosphoinositide-3-kinase (PI3Ks) family of lipid kinases is widely conserved from yeast to mammals. In this work, we identified a total of 14 members of the PI3Ks from the channel catfish genome and transcriptome and conducted phylogenetic and syntenic analyses of these genes. The expression profiles after infection with Edwardsiella ictaluri and Flavobacterium columnare were examined to determine the involvement of PI3Ks in immune responses after bacterial infection in catfish. The results indicated that PI3Ks genes including all of the catalytic subunit and several regulatory subunits genes were widely regulated after bacterial infection. The expression patterns were quite different when challenged with different bacteria. The PI3Ks were up-regulated rapidly at the early stage after ESC infection, but their induced expression was much slower, at the middle stage after columnaris infection. RNA-Seq datasets indicated that PI3K genes may be expressed at different levels in different catfish differing in their resistance levels against columnaris. Future studies are required to confirm and validate these observations. Taken together, this study indicated that PI3K genes may be involved as a part of the defense responses of catfish after infections, and they could be one of the determinants for disease resistance. [ABSTRACT FROM AUTHOR]

• A load-balanced domain decomposition algorithm for 3D embedded unstructured grids. • Implementation of parallel simulations for embedded discrete fracture model. • Discussion on inter-processor communication patterns of embedded discrete fracture model. • Satisfactory scalability and parallel efficiency for a two-phase flow model with up 36 million grids on 1024 CPU cores. Recently, embedded discrete fracture model (EDFM) using non-conforming staggered 3D unstructured grids was presented for the numerical simulation of fluid-flows in large-scale complex fractured porous media. In this paper, we implement load-balanced parallel simulations for this approach on distributed memory systems. A load-balanced domain decomposition algorithm is presented to partition matrix grids and embedded fracture grids uniformly. We classify all grid connections on the boundary of subdomains to five types and illustrate corresponding inter-processor connections. A packaged inter-processor communication approach is implemented based on message passing interface (MPI) to improve communication efficiency for this simulation method. A two-phase parallel simulator is developed, and block coupled method is adopted to assemble the equations discretized in matrix and grid domains using two-point flux approximation (TPFA) finite volume method. The load-balanced algorithm is tested by nonuniformly distributed fracture networks. The performance and scalability are also tested on 1024 CPU cores by two complex fracture network models with up to 25 million matrix grids and 11 million embedded fracture grids. The results show satisfactory parallel efficiency and scalability. [ABSTRACT FROM AUTHOR]

• An improved embedded discrete fracture model for 3D unstructured grids. • Efficient and robust domain connectivity algorithms for 3D unstructured grids. • Block coupled solving method for overlapping matrix and fracture domains. • Tested for solving two-phase flow in a field-scale highly complex fracture network. Numerical simulation in 3D complex fractured media is challenging as the geometric discretization of porous media and fracture domains is on multiple scales. In this paper, we present an improved embedded discrete fracture model (EDFM) for 3D unstructured non-matching grids, and correspondingly efficient and robust domain connectivity algorithms are developed. Unlike traditional EDFM, improved EDFM is capable to simulate flows on 3D staggered overlapping unstructured matrix and fracture grids. We illustrate flux exchange patterns and formulas of improved EDFM. Two types of domain connectivity are built to assemble hybrid dimensional overlapping grids of matrix and fracture domains to a coupled linear system using finite volume method. Building domain connectivity is an important challenge for 3D hybrid-dimensional unstructured non-matching grids. We classify all points of domain connectivity into three types. A face indexed octree is employed for spatial binary search. Two types of grid adjacency information are used to accelerate the calculation of grid intersection points. Fracture-matrix intersection information is adopted to accelerate fracture-fracture connectivity generation. The performance of the algorithms is tested by 8 cases in different scales and compared with traversal method. Improved EDFM is validated against discrete fracture model and traditional EDFM using a two-phase flow solver. A case with highly complex fracture network is simulated to demonstrate the capacity of improved EDFM in real complex physical problems. The effects of grid type and resolution are also analyzed in this work. [ABSTRACT FROM AUTHOR]

Abstract: Numerical simulation in naturally fractured media is challenging because of the coexistence of porous media and fractures on multiple scales that need to be coupled. We present a new approach to reservoir simulation that gives accurate resolution of both large-scale and fine-scale flow patterns. Multiscale methods are suitable for this type of modeling, because it enables capturing the large scale behavior of the solution without solving all the small features. Dual-porosity models in view of their strength and simplicity can be mainly used for sugar-cube representation of fractured media. In such a representation, the transfer function between the fracture and the matrix block can be readily calculated for water-wet media. For a mixed-wet system, the evaluation of the transfer function becomes complicated due to the effect of gravity. In this work, we use a multiscale finite element method (MsFEM) for two-phase flow in fractured media using the discrete-fracture model. By combining MsFEM with the discrete-fracture model, we aim towards a numerical scheme that facilitates fractured reservoir simulation without upscaling. MsFEM uses a standard Darcy model to approximate the pressure and saturation on a coarse grid, whereas fine scale effects are captured through basis functions constructed by solving local flow problems using the discrete-fracture model. The accuracy and the robustness of MsFEM are shown through several examples. In the first example, we consider several small fractures in a matrix and then compare the results solved by the finite element method. Then, we use the MsFEM in more complex models. The results indicate that the MsFEM is a promising path toward direct simulation of highly resolution geomodels. [Copyright &y& Elsevier]

Abstract: Defining the pathways required for keratinocyte cell migration is important for understanding mechanisms of wound healing and tumor cell metastasis. We have recently identified an α6β4 integrin-Rac1 signaling pathway via which the phosphatase Slingshot (SSH) activates/dephosphorylates cofilin, thereby determining keratinocyte migration behavior. Here, we assayed the role of 14-3-3 isoforms in regulating the activity of SSH1. Using amino or carboxy terminal domains of 14-3-3ζ, we demonstrate that in keratinocytes 14-3-3ζ/τ heterodimers bind SSH1, in the absence of Rac1 signaling. This interaction leads to an inhibition of SSH1 activity, as measured by an increase in phosphorylated cofilin levels. Overexpression of the carboxy terminal domain of 14-3-3ζ acts as a dominant negative and inhibits the interaction between 14-3-3τ and SSH1. These results implicate 14-3-3ζ/τ heterodimers as key regulators of SSH1 activity in keratinocytes and suggest they play a role in cytoskeleton remodeling during cell migration. [Copyright &y& Elsevier]

Abstract: The loss of independent joint control in the paretic upper limb is a cardinal sign of movement disorders following stroke. However, the underlying neural mechanisms for such a loss following stroke are still largely unknown. In order to investigate the possible contribution of altered sensorimotor cortical activity to the loss of independent joint control, we measured electroencephalographic (EEG) and torque signals during the generation of static shoulder/elbow torques. We found significant increases in the overlap of shoulder and elbow joint representations at the cortical level in stroke subjects as compared to control subjects. Linear regression results demonstrated significant associations between the cortical overlap of joint representations and the degree of the loss of independent joint control. Therefore, we conclude that an increased overlap of cortical representations for shoulder and elbow contributes to the expression of the loss of independent shoulder/elbow control of the paretic upper limb in chronic hemiparetic stroke survivors. [Copyright &y& Elsevier]

[Display omitted] • In this study, MIL-101(Cr) was applied to nucleic acid adsorption and ATP detection. • The quenching mechanism of MIL-101(Cr) was studied deeply. • This strategy adopted aptamer/enzyme assisted cyclic amplification to promote ATP test. • Successfully designed the "AND" logic gate. With the development of frame materials, metal organic frameworks (MOFs) have been successfully applied in the fields of biological small molecule analysis and fluorescent DNA detection. In this work, in view of the good adsorption characteristics of MIL-101(Cr), the highly sensitive detection of adenosine triphosphate (ATP) assisted nucleic acid exonuclease amplification by MIL-101(Cr) on the different affinity of single stranded DNA and double stranded DNA was investigated. The detection limit of ATP reaches 1.7 μM, and the platform has good applicability in biological samples. On this basis, an "AND" logic gate was successfully constructed. Superior sensitivity to ATP in the presence of exonuclease was reflected, which greatly enhanced the system's fluorescence. Importantly, the fluorescence sensing application of this nanomaterial inspired other target detection and enriched the building blocks of fluorescence sensing platform. [ABSTRACT FROM AUTHOR]

Abstract: Accumulation of GABAA receptors (GABAARs) at GABAergic synapses requires the cytoplasmic loop region and C-terminal transmembrane domain of the receptor γ2 subunit. We here report a novel interaction of γ2 with Calcium-Modulating cyclophilin Ligand (CAML), an integral membrane protein that regulates this mechanism. Interaction of GABAARs with CAML depends on both the cytoplasmic region and fourth transmembrane domain of the γ2 subunit, CAML immunoprecipitates with GABAARs from transfected cells and brain lysates and colocalizes with γ2 in ER vesicles in soma and dendrites of neurons. CAML shRNA treatment results in reduced expression of postsynaptic GABAARs, along with significant reductions in GABA-evoked whole cell currents and GABAergic synaptic function, while glutamatergic transmission is unaffected. Reduced surface expression of GABAARs in CAML mutant neurons is associated with selective deficits in recycling of endocytosed GABAARs to the cell surface. Our results indicate a specific role of CAML in functional expression and endocytic recycling of postsynaptic GABAARs. [Copyright &y& Elsevier]

Abstract: Some research has reported interaction between polyamidoamine dendrimers or polyethylenimine and quantum dots causing a quantum yield decrease of quantum dots. In this work, however, polyethylenimines of different molecular weight that were used to modify CdS quantum dots gave rise to the enhancement of CdS quantum yield to nearly 100%. Herein, we present the synthesis of a kind of easily prepared high-quantum-yield CdS quantum dot in aqueous solution and the study of the interaction between CdS and polyethylenimine. [Copyright &y& Elsevier]

Abstract: Alzheimer’s patients have increased levels of both the 42 beta amyloid-β-peptide (Aβ) and amyloid binding alcohol dehydrogenase (ABAD) which is an intracellular binding site for Aβ. The over-expression of Aβ and ABAD in transgenic mice has shown that the binding of Aβ to ABAD results in exaggerating neuronal stress and impairment of learning and memory. From a proteomic analysis of the brains from these animals we identified that peroxiredoxin II levels increase in Alzheimer’s diseased brain. This increase in peroxiredoxin II levels protects neurons against Aβ induced toxicity. We also demonstrate, for the first time in living animals, that the expression level of peroxiredoxin II is an indicator for the interaction of ABAD and Aβ as its expression levels return to normal if this interaction is perturbed. Therefore this indicates the possibility of reversing changes observed in Alzheimer’s disease and that the Aβ–ABAD interaction is a suitable drug target. [Copyright &y& Elsevier]

Abstract: The HDAC inhibitor Trichostatin A (TSA) exhibits antitumour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113 cells by inducing G2/M arrest, apoptosis, up-regulation of the pro-apoptotic protein Bax and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-XL which are regulated by the transcription factor nuclear factor (NF)-κB. Coincident with this observation, TSA induced a concentration-dependent reduction of constitutive and tumour necrosis factor (TNF)-α-induced NF-κB activation in Tca8113 cells. This induction was correlated with decreased phosphorylation and increased expression of inhibitors of NF-κB (IκB)α induced by TSA. Overall, our results indicate inhibition of NF-κB activation contributes, at least partially, to the antitumour activity of TSA in human tongue carcinoma cells. [Copyright &y& Elsevier]

Abstract: Different cortical source localization methods have been developed to directly link the scalp potentials with the cortical activities. Up to now, these methods are the only possible solution to noninvasively investigate cortical activities with both high spatial and time resolutions. However, the application of these methods is hindered by the fact that they have not been rigorously evaluated nor compared. In this paper, the performances of several source localization methods (moving dipoles, minimum Lp norm, and low resolution tomography (LRT) with Lp norm, p equal to 1, 1.5, and 2) were evaluated by using simulated scalp EEG data, scalp somatosensory evoked potentials (SEPs), and upper limb motor-related potentials (MRPs) obtained on human subjects (all with 163 scalp electrodes). By using simulated EEG data, we first evaluated the source localization ability of the above methods quantitatively. Subsequently, the performance of the various methods was evaluated qualitatively by using experimental SEPs and MRPs. Our results show that the overall LRT Lp norm method with p equal to 1 has a better source localization ability than any of the other investigated methods and provides physiologically meaningful reconstruction results. Our evaluation results provide useful information for choosing cortical source localization approaches for future EEG/MEG studies. [Copyright &y& Elsevier]

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study. Approximately 88.31% of 100 mg/L Cr(VI) was continuously removed within 72 h, while it could resist up to 300 mg/L Cr(VI). Metal ions Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance to 14.41% and 3.41% under the optimal conditions, respectively. Cr(VI) removal performances by subcellular extracts showed that nearly 45.28% of 100 mg/L extracellular Cr(VI) was efficaciously reduced to Cr(III), while only 14.27%, 6.40%, and 2.73% of the cell-free extract, resting cells, and cell debris were reduced, respectively. This suggested that extracellular bioreduction was the primary Cr(VI) detoxification strategy despite a small part of Cr(VI) reduction took place intracellularly. In particular, the reduction products of the intracellular and extracellular compounds significantly differed, with organo-Cr(III) complex outside the cell and crystalline Cr(III) precipitate inside. Such observation was also evidenced by the intracellular black precipitate observed in the TEM image. XRD, XPS, and EPR analysis showed different Cr(III) compositions of intracellular and extracellular products. This study deepens our insights into the different fates of microorganisms that reduce Cr(VI) intracellularly and extracellularly. • Extracellular bioreduction was main Cr(VI) detoxification strategies by the newly isolated Bacillus sp. HL1. • Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance. • Extracellular organo-Cr(III) complex and intracellular crystalline Cr(III) precipitate were the main reduced products. [ABSTRACT FROM AUTHOR]

A luminescent zinc metal-organic framework with uncoordinated triazolate N-donors, namely [Zn (tba) 2 ]·DMA (1 , DMA ​= ​ N , N -dimethylacetamide), has been successfully synthesized under solvothermal conditions by using a triazolate-carboxylate bifunctional ligand, 4-(1 H -1,2,4-triazol-1-yl)benzoic acid (Htba). Single-crystal X-ray diffraction analysis reveals that compound 1 displays a 4-fold interpenetrating dia framework with 1D dumbbell-shaped channels. The systematic luminescence experiments reveal that 1 can be potentially used as a fast-response fluorescence sensor for the sensitive detection of nitrobenzene and Fe3+ ion through drastic fluorescence quenching. Moreover, the quenching mechanisms of 1 towards nitrobenzene and Fe3+ were also investigated. A luminescent zinc metal-organic framework with a 4-fold interpenetrating dia network can be used as a fast-response fluorescence sensor for the sensitive detection of nitrobenzene and Fe3+ ion through drastic fluorescence quenching. Image 1 • A new luminescent MOF based on a triazolate-carboxylate bifunctional ligand have been synthesized. • The framework exhibits a 4-fold interpenetrating dia framework with 1D dumbbell-shaped channels. • The framework can be used as a fast-response fluorescence sensor for detection of nitrobenzene and Fe3+. [ABSTRACT FROM AUTHOR]

Terracing and rainfall characteristics notably influence the water erosion processes. However, an extensive long term in situ quantitative evaluation of the approaches to control the water erosion in different orchard terraces has not yet been performed, especially considering the increasing frequency and severity of extreme rainfall events due to the global climate change. In this study, six types of orchard terraces, including slope land as the control (SLck), level terrace with bare (LTb) and vegetation taluses (LTv), outward (OTv) and inward terrace (ITv) with vegetation taluses and level terrace having front mounds and back ditches with vegetation taluses (MDLTv), were used to analyze the effects of extreme and ordinary rainfall events on the surface runoff and soil erosion. According to the measured data for twelve consecutive years, 356 natural rainfall events were divided into extreme and ordinary rainfall, based on the World Meteorological Organization standard. The results indicated that more severe surface runoff and sediment loss occurred under extreme rainfall: the runoff coefficient and soil loss under extreme rainfall were 2.6 and 11.5 times those under ordinary rainfall, respectively. The sediment yield (contribution rate, 42.9%) exhibited a higher sensitivity to extreme rainfall events compared to that of the surface runoff generation (contribution rate, 16.4%). Moreover, the reduction in the surface runoff and sediment in the extreme rainfall case differed for different orchard terraces. The average surface runoff coefficient and soil loss amount decreased in the following order: SLck>LTb>OTv>LTv>ITv>MDLTv. Nevertheless, the highest and lowest contributions of the extreme rainfall to the sediment yield occurred in the LTb (64.8%) and MDLTv (21.7%) plots, respectively. Therefore, severe talus erosion caused by extreme rainfall should be monitored, and a combination of vegetation taluses and front mounds and back ditches on the platforms is recommended as a sustainable strategy to prevent extreme water erosion when transforming slope land into orchard terraces. • Terraces reduce substantially water erosion, especially with vegetation taluses. • Extreme rainfall events facilitate the occurrence of runoff and soil erosion. • MDLTv is most efficient terracing measure to prevent extreme water erosion. [ABSTRACT FROM AUTHOR]

Nonferrous metal mining activities produce enormous amounts of tailings that contain high concentrations of toxic chemicals threatening human health and the environment. This risk could be alleviated using remediation agents such as biochar, as proposed by others. However, contradictory evidence indicates that biochar can increase or sometimes decrease bioavailable concentrations depending on the selection of metal(loid)s in mine tailings. Here three biochars derived from different raw stocks were used to treat mine tailings samples. Chemical analyses indicated that all biochars favored the stabilization of Cd, Cr, Cu, Pb, and Zn, as well as the mobilization of As and Sb. The barley root elongation bioassay showed that the tailings toxicity was only partially diminished (up to 55.8%) or even elevated (up to 20.7%) by biochar treatment. Similar results were also observed from microbial enzyme assays (increased up to 28.3% or decreased up to 24.0%). Further analyses showed that these toxic effects correlated well with the relative toxicity index (R 2 = 0.66 to 0.88). Toxicity testing coupled with the use of a toxicity prediction model presented here suggested that the release of As and Sb from tailings compromised the favorable effects of biochar treatment on toxic cationic metals. Such information is of paramount importance when taking countermeasures for improving bioremediation technologies. Image 1 • Biochar decreased mobility of metals and increased that of metalloids in tailings. • Phytotoxicity was diminished < 55.8% or increased < 20.7% using different biochars. • Microbial activities increased < 28.3% or decreased < 24.0% using different biochars. • Release of metalloids compromised biochar treatment on mine tailings. • Relative toxicity index can predict tailings mixture toxicity. [ABSTRACT FROM AUTHOR]

Although most activities of daily life require simultaneous coordination of both proximal and distal joints, motor preparation during such movements has not been well studied. Previous results for motor preparation have focused on hand/finger movements. For simple hand/finger movements, results have found that such movements typically evoke activity primarily in the contralateral motor cortices. However, increasing the complexity of the finger movements, such as during a distal sequential finger-pressing task, leads to additional recruitment of ipsilateral resources. It has been suggested that this involvement of the ipsilateral hemisphere is critical for temporal coordination of distal joints. The goal of the current study was to examine whether increasing simultaneous coordination of multiple joints (both proximal and distal) leads to a similar increase in coupling with ipsilateral sensorimotor cortices during motor preparation compared to a simple distal movement such as hand opening. To test this possibility, 12 healthy individuals participated in a high-density EEG experiment in which they performed either hand opening or simultaneous hand opening while lifting at the shoulder on a robotic device. We quantified within- and cross-frequency cortical coupling across the sensorimotor cortex for the two tasks using dynamic causal modeling. Both hand opening and simultaneous hand opening while lifting at the shoulder elicited coupling from secondary motor areas to primary motor cortex within the contralateral hemisphere exclusively in the beta band, as well as from ipsilateral primary motor cortex. However, increasing the task complexity by combining hand opening while lifting at the shoulder also led to an increase in cross-frequency coupling within the ipsilateral hemisphere including theta, beta, and gamma frequencies, as well as a change in the coupling frequency of the interhemispheric coupling between the primary motor and premotor cortices. These findings demonstrate that increasing the demand of joint coordination between proximal and distal joints leads to increases in communication with the ipsilateral hemisphere as previously observed in distal sequential finger tasks. • EEG was measured to analyze frequency coupling during motor preparation using DCM. • Complexity was manipulated to examine changes in coupling with ipsilateral cortex. • Addition of lifting led to increased coupling with ipsilateral sensorimotor cortex. • Coupling expanded from beta to theta and gamma bands with the addition of lifting. • Increasing the number of joints controlled increases reliance on ipsilateral cortex. [ABSTRACT FROM AUTHOR]

[Display omitted] Metal-organic polymers (MOPs) can enhance the photoelectrochemical (PEC) water oxidation performance of BiVO 4 photoanodes, but their PEC mechanisms have yet to be comprehended. In this work, we constructed an active and stable composite photoelectrode by overlaying a uniform MOP on the BiVO 4 surface using Fe2+ as the metal ions and 2,5-dihydroxyterephthalic acid (DHTA) as ligand. Such modification on the BiVO 4 surface yielded a core-shell structure that could effectively enhance the PEC water oxidation activity of the BiVO 4 photoanode. Our intensity-modulated photocurrent spectroscopy analysis revealed that the MOP overlayer could concurrently reduce the surface charge recombination rate constant (k sr) and enhance the charge transfer rate constant (k tr), thus accelerating water oxidation activity. These phenomena can be ascribed to the passivation of the surface that inhibits the recombination of the charge carrier and the MOP catalytic layer that improves the hole transfer. Our rate law analysis also demonstrated that the MOP coverage shifted the reaction order of the BiVO 4 photoanode from the third-order to the first-order, resulting in a more favorable rate-determining step where only one hole accumulation is required to overcome water oxidation. This work provides new insights into the reaction mechanism of MOP-modified semiconductor photoanodes. [ABSTRACT FROM AUTHOR]

In our previous study, Oxysterol-binding protein-related protein 2 (OSBPL2) was first identified as a new deafness-causative gene contribute to non-syndromic hearing loss. However, the underlying mechanism of OSBPL2 -induced hearing loss remains unknown. Here, we used hearing-specific cells and tissues OC-1 cells and zebrafish inner ear tissues as models to identify common transcriptome changes in genes and pathways in the absence of human OSBPL2 orthologues by RNA-seq analysis. In total, 2112 differentially expressed genes (DEGs) were identified between wild-type (WT) and Osbpl2 −/− OC-1 cells, and 877 DEGs were identified between WT and osbpl2b −/- zebrafish inner ear tissues. Functional annotation implicated Osbpl2/osbpl2b in lipid metabolism, cell adhesion and the extracellular matrix in both OC-1 cells and zebrafish inner ear tissues. Protein–protein interaction (PPI) analysis indicated that Osbpl2/osbpl2b were also involved in ubiquitination. Further experiments showed that Osbpl2 −/− OC-1 cells exhibited an abnormal focal adhesion morphology characterized by inhibited FAK activity and impaired cell adhesion. In conclusion, we identified novel pathways modulated by OSBPL2 orthologues, providing new insight into the mechanism of hearing loss induced by OSBPL2 deficiency. • Osbpl2 / osbpl2b defects enrich ECM-receptor interaction and focal adhesion in OC-1 cells and zebrafish inner ear tissues. • The activity of FAK is inhibited in Osbpl2 −/− OC-1 cells. • Novel pathways are identified to be modulated by OSBPL2 orthologues. [ABSTRACT FROM AUTHOR]

The growing global demand for non-ferrous metals has led to serious environmental issues involving uncovered mine site slag dumps that threaten the surrounding soils, surface waters, groundwater, and the atmosphere. Remediation of these slags using substitute cement materials for ordinary Portland cement (OPC) and precursors for alkali-activated materials (AAMs) can convert hazardous solid wastes into valuable construction materials, as well as to attain the desired solidification and stabilization (S/S) of heavy metal(loid)s (HM). This review discusses the current research on the effect of non-ferrous slags on the reaction mechanisms of the OPC and AAM. The S/S of HM from the non-ferrous slags in AAM and OPC is also reviewed. HM can be stabilized in these materials based on the complex salt effect and isomorphic effects. The major challenges faced in AAMs and OPC for HM stabilization include the long-term durability of the matrix (e.g., sulfate attack, stability of volume). The existing knowledge gaps and future trends for the sustainable application of non-ferrous slags are also discussed. [Display omitted] • The effect of non-ferrous slags on reaction mechanisms of the OPC and AAM was discussed. • The S/S of HM from the non-ferrous slags in AAM and OPC were reviewed. • The long-term durability of the AAMs and OPC for HM stabilization were proposed. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we propose a locally conservative Galerkin (LCG) finite element method for two-phase flow simulations in heterogeneous porous media. The main idea of the method is to use the property of local conservation at steady state conditions in order to define a numerical flux at element boundaries. It provides a way to apply standard Galerkin finite element method in two-phase flow simulations in porous media. The LCG method has all the advantages of the standard finite element method while explicitly conserving fluxes over each element. All the examples presented show that the formulation employed is accurate and robust, while using less CPU time than finite volume method. [Copyright &y& Elsevier]

GPRASP2 is implicated in nervous system diseases, tumors and immune inflammation. In our previous study, G protein-coupled receptor associated sorting protein 2 (GPRASP2) was identified as a novel causal gene for X-linked recessive syndromic hearing loss (SHL). However, the role of GPRASP2 in auditory function has not been elucidated. The Gprasp2 -knockout (KO) mouse HEI-OC1 auditory cells were constructed using CRISPR/Cas9-mediated gene editing. RNA-sequencing (RNA-seq) was used to investigate the differentially expressed genes (DEGs) and DEGs-enriched signaling pathways, which was verified by Western blot. Flow cytometry assay was used to examine cell apoptosis. The cytological pathology was evaluated by laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). Mitochondrial damage was observed in Gprasp2 -KO HEI-OC1 cells. RNA-seq analysis suggested that Gprasp2 -KO was implicated in the apoptosis process, which could be mediated by Hedgehog (Hh) signaling pathway. The key molecules in Hh signaling pathway (Smo, Gli1, Gli2) were detected to be down-regulated in Gprasp2 -KO HEI-OC1 cells. The differential expression of apoptosis molecules (Bcl2, Bax, Caspase-3/cleaved-Caspase-3) indicated that Gprasp2 -KO induced apoptosis in HEI-OC1 cells. The treatment of smoothened agonist (Purmorphamine, PUR) activated the Hh-Gli signaling pathway and reduced apoptosis in Gprasp2 -KO HEI-OC1 cells. This study revealed that Gprasp2 -disruption inhibited Hh signaling pathway and led to cell apoptosis in HEI-OC1 cells, which might provide the potential molecular mechanism of GPRASP2 mutation associated with human SHL. • Gprasp2 disruption induced mitochondrial damage and apoptosis in HEI-OC1 cells. • Gprasp2 disruption inhibited Hedgehog signaling pathway in HEI-OC1 cells. • The smoothened agonist could reduce apoptosis in Gprasp2 -knockout HEI-OC1 cells. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) are key regulators of gene expression and perform critical roles in various biological processes. To investigate the functional roles of miRNAs in the prolactin receptor (PRLR) signaling pathway in breast cancer, we constructed two small RNA libraries from human breast cancer T-47D cells treated with or without prolactin (PRL). The miRNA expression profiles were systematically screened using Solexa deep-sequencing technology. More than 40 miRNAs were significantly differentially expressed, from which 4 miRNAs were chosen for validation by stem-loop real-time PCR. In addition, 3 novel miRNAs were selected for verification by PCR. Furthermore, upstream miRNA target genes were predicted using different algorithms, GO and KEGG analyses revealed that these targets were highly related to the PRLR signaling pathway. This study provides a reference for elucidating the complex miRNA-mediated regulatory networks of PRL/PRLR signaling pathway that affect breast cancer tumorigenesis and progression. [Copyright &y& Elsevier]

Exercise training is one of the major non-pharmacological treatments for hypertension. However, the central mechanism by which exercise training attenuates the hypertensive responses remains unclear. Irisin is a muscle-secreted cytokine derived from fibronectin type III domain containing 5 (FNDC5) that will be released into the circulation during exercise. We hypothesized that irisin may play a role in the blood pressure regulation by exercise. To examine the hypothesis, our study investigated the effect of irisin on hypertension and its central mechanism. The study was performed in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats. We found that intravenous injection of irisin effectively reduced blood pressure, plasma norepinephrine, paraventricular nucleus (PVN) levels of neuronal activation, oxidative stress and inflammation in SHRs. Moreover, irisin activated nuclear factor E2-related factor-2 (Nrf2) and restored the imbalance of neurotransmitters in the PVN. Our study also found PVN knockdown of Nrf2 abolished the protective effects of irisin on hypertension. These findings demonstrate irisin can improve hypertension via Nrf2-mediated antioxidant in the PVN. [ABSTRACT FROM AUTHOR]

A phase-field moving contact line model is presented for a two-phase system with soluble surfactants. With the introduction of some scalar auxiliary variables, the original free energy functional is transformed into an equivalent form, and then a new governing system is obtained. The resulting model consists of two Cahn–Hilliard-type equations and incompressible Navier–Stokes equation with variable densities, together with the generalized Navier boundary condition for the moving contact line. We prove that the proposed model satisfies the total energy dissipation with time. To numerically solve such a complex system, we develop a nonlinearly coupled scheme with unconditional energy stability. A splitting method based on pressure stabilization is used to solve the Navier–Stokes equation. Some subtle implicit–explicit treatments are adopted to discretize convection and stress terms. A stabilization term is artificially added to balance the explicit nonlinear term associated with the surface energy at the fluid–solid interface. We rigorously prove that the proposed scheme can preserve the discrete energy dissipation. An efficient finite difference method on staggered grids is used for the spatial discretization. Numerical results in both two and three dimensions demonstrate the accuracy and energy stability of the proposed scheme. Using our model and numerical scheme, we investigate the wetting behavior of droplets on a solid wall. Numerical results indicate that surfactants can affect the wetting properties of droplet by altering the value of contact angles. [ABSTRACT FROM AUTHOR]

Osteoclast activation by wear particles has caused major difficulties for surgeons. Wear particles are the main causes of aseptic prosthetic loosening. Gö6983, a protein kinase C inhibitor, inhibits five subtypes of protein kinase C family members. Here, we found that Gö6983 had an obviously inhibitory effect on wear-particles-induced osteolysis in vivo . In vitro , Gö6983 inhibited RANKL-stimulated osteoclast formation and function by inhibiting the RANKL-stimulated nuclear factor-κB/JNK/p38 signaling pathway. We also observed that Go6983 had no effect on the differentiation of osteoblasts and osteoblast-associated genes expression. According to our data, Gö6983 has potential therapeutic effects for aseptic prosthetic loosening caused by osteoclast activation. [ABSTRACT FROM AUTHOR]

The thermostable Geobacillus stearothermophilus GsI–IIC intron is among the few bacterial group II introns found to proliferate to high copy number in its host genome. Here, we developed a bacterial genetic assay for retrohoming and biochemical assays for protein-dependent and self-splicing of GsI–IIC. We found that GsI–IIC, like other group IIC introns, retrohomes into sites having a 5′-exon DNA hairpin, typically from a bacterial transcription terminator, followed by short intron-binding sequences (IBSs) recognized by base pairing of exon-binding sequences (EBSs) in the intron RNA. Intron RNA insertion occurs preferentially but not exclusively into the parental lagging strand at DNA replication forks, using a nascent lagging strand DNA as a primer for reverse transcription. In vivo mobility assays, selections, and mutagenesis indicated that a variety of GC-rich DNA hairpins of 7–19 bp with continuous base pairs or internal elbow regions support efficient intron mobility and identified a critically recognized nucleotide (T-5) between the hairpin and IBS1, a feature not reported previously for group IIC introns. Neither the hairpin nor T-5 is required for intron excision or lariat formation during RNA splicing, but the 5′-exon sequence can affect the efficiency of exon ligation. Structural modeling suggests that the 5′-exon DNA hairpin and T-5 bind to the thumb and DNA-binding domains of GsI–IIC reverse transcriptase. This mode of DNA target site recognition enables the intron to proliferate to high copy number by recognizing numerous transcription terminators and then finding the best match for the EBS/IBS interactions within a short distance downstream. [ABSTRACT FROM AUTHOR]

Objectives: It is well known that cancer patients with concurrent venous thromboembolism (VTE) have poorer oncologic outcomes. Even though 25-40% of ovarian cancer patients develop a VTE, the role of tumor-specific molecular factors in VTE development is not known. Therefore, we aimed to perform a comprehensive multi-platform omics analysis to identify factors in ovarian cancer that could be related to the development of VTE or the associated impact on patient outcomes. Methods: Patients diagnosed with high-grade serous ovarian carcinoma (HGSOC) between 2013 and 2019 with frozen tissue and matched germline blood samples available were screened for a concurrent diagnosis of VTE. We performed a multiplatform omics analysis, including bulk RNA sequencing (RNA-seq), proteomics, and DNA whole-exome sequencing (WES), followed by integrated analysis on a total of 32 patient samples (n =16, VTE; n =16, non-VTE as controls). Bioinformatics analyses were then carried out to identify potential molecular abnormalities that could contribute to the pathology of VTE in ovarian cancer. Results: The timing of VTE varied across the 16 cases of VTE, ranging from the onset at the time of diagnosis of ovarian cancer (n =9; 56%), during neoadjuvant chemotherapy (NACT; n =2, 12.5%), and within 28 days of surgery or during adjuvant chemotherapy (n =5; 31.3%). The average overall survival (OS) of patients with VTE was 2.05 years (SD: 1.35); however, OS for the control group could not be calculated since more than 80% (n =13, 81.3%) are still alive with the disease after a mean of 3.5 years (SD: 1.07). RNA-seq analysis revealed 130 differentially expressed genes in VTE versus control. Most notably, the F3 gene, which encodes tissue factors, was upregulated in nearly all VTE samples compared to controls. A Cox regression using age, grade, and gene expression indicated an association with worse overall survival for GAPDHP65 and NRSN2-AS1 with hazard ratios of >1.5 (p=0.018 and p<0.001, respectively). On proteomics analysis, we quantified over 7,300 proteins in VTE versus control, of which 255 were significantly altered (p<0.01). Principal component analysis showed that these altered proteins explained 47.5% of the variance between groups. They did not demonstrate a relationship with the onset of VTE timing, suggesting tumor-mediated changes independent of ovarian cancer treatment status. Among the significantly altered putative drug targets, we identified platelet-derived growth factor subunit B (PDGFB) elevated nearly tenfold in the VTE versus the control group. We also observed a profound trend of increased collagen 1A1 and 3A1 in the VTE group. The proteins elevated in the VTE group were biased towards an expression within the extracellular space. Integrated analyses with RNA-seq data indicate a strong correlation of protein and transcript abundance in 64 candidate proteins (Spearman Rho=0.677, p<0.0001). WES analysis revealed predominantly missense mutations in the form of single-nucleotidepolymorphisms (SNPs). Several distinct genes were mutated within the VTE cohort compared to the control group; however, these did not reach statistical significance, likely due to the small sample size. Conclusions: We provide the first multiplatform comprehensive multi-omics analysis of HGSOC based on VTE development. These findings suggest substantial molecular differences in tumors from patients who develop VTE compared to those that do not. These findings could have implications for risk stratification and preventative and treatment strategies for VTE. [ABSTRACT FROM AUTHOR]

Chemokines are a superfamily of structurally related chemotactic cytokines exerting significant roles in regulating cell migration and activation. They are defined by the presence of four conserved cysteine residues and are divided into four subfamilies depending on the arrangement of the first two conserved cysteines residues: CXC, CC, C and CX3C. In this study, a complete set of 17 CXC chemokine ligand (CXCL) genes was systematically identified and characterized from channel catfish genome through data mining of existing genomic resources. Phylogenetic analysis allowed annotation of the 17 CXC chemokines. Extensive comparative genomic analyses supported their annotations and orthologies, revealing the existence of fish-specific CXC chemokines and the expansion of CXC chemokines in the teleost genomes. The analysis of gene expression after bacterial infection indicated the CXC chemokines were expressed in a gene-specific manner. CXCL11.3 and CXCL20.3 were expressed significantly higher in resistant fish than in susceptible fish after ESC infection, while CXCL20.2 were expressed significantly higher in resistant fish than in susceptible fish after columnaris infection. The expression of those CXC chemokines, therefore can be a useful indicator of disease resistance. A similar pattern of expression was observed between resistant and susceptible fish with biotic and abiotic stresses, ESC, columnaris and hypoxia, suggesting that high levels of expression of the majority of CXC chemokines, with exception of CXC11 and CXC20, are detrimental to the host. [ABSTRACT FROM AUTHOR]

As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD. ETS-1 expression was examined in IBD patients. CD45RBhighCD4+ T cell-transfer colitis, dextran sulfate sodium (DSS)-induced colitis, and azomethane (AOM)/DSS-induced colitis-associated cancer (CAC) models were constructed to probe the function of ETS-1 in vivo. RNA-sequencing of CD4+ T cells from Ets-1 transgenic (Tg) mice was performed to decipher the key differentially expressed genes. Adenovirus transduction was conducted to verify the therapeutic potentials of ETS-1 in vivo. ETS-1 expression was significantly increased in CD4+ T cells from active IBD patients compared with healthy controls, which was upregulated by TNF-α but markedly suppressed by anti -TNF-α mAb therapy. More severe colitis was observed in Rag1 −/− mice reconstituted with Ets-1TgCD45RBhighCD4+ T cells or in Ets- 1 Tg mice after DSS exposure compared with controls, characterized by higher TNF-α and IFN-γ expression in inflamed colon. Ets- 1 Tg mice were more prone to develop AOM/DSS-induced CAC, and bone marrow chimeras further proved that lamina propria immune cells but not intestinal epithelial cells contributed to the development of colitis. RNA-sequencing and luciferase analysis revealed cold-inducible RNA-binding protein (CIRBP) as a functional target of ETS-1 to promote Th1 cell-driven immune response. Consistently, intraperitoneal administration of adenovirus-m- cirbp -shRNA ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colitis of Ets- 1 Tg mice. Our data identify that ETS-1 is highly expressed in IBD patients and promotes Th1-driven mucosal inflammation through CIRBP. CIRBP may serve as a novel therapeutic target for treatment of human IBD. [Display omitted] • ETS-1 is highly expressed in CD4+ T cells of IBD patients and facilitates Th1 cell differentiation. • Overexpression of ETS-1 in CD4+ T cells promotes colitis and colitis-associated cancer in mice. • ETS-1 facilitates CIRBP expression to induce Th1 cell-associated intestinal inflammation. • Blockade of CIRBP ameliorates murine colitis and CIRBP may be a novel therapeutic approach in treatment of human IBD. [ABSTRACT FROM AUTHOR]

Heat shock proteins 70/110 (Hsp70/110) are a family of conserved ubiquitously expressed heat shock proteins which are produced by cells in response to exposure to stressful conditions. Besides the chaperone and housekeeping functions, they are also known to be involved in immune response during infection. In this study, we identified 16 Hsp70/110 geness in channel catfish ( Ictalurus punctatus ) through in silico analysis using RNA-Seq and genome databases. Among them 12 members of Hsp70 (Hspa) family and 4 members of Hsp110 (Hsph) family were identified. Phylogenetic and syntenic analyses provided strong evidence in supporting the orthologies of these HSPs. In addition, we also determined the expression patterns of Hsp70/110 genes after Flavobacterium columnare and Edwardsiella ictaluri infections by meta-analyses, for the first time in channel catfish. Ten out of sixteen genes were significantly up/down-regulated after bacterial challenges. Specifically, nine genes were found significantly expressed in gill after F. columnare infection. Two genes were found significantly expressed in intestine after E. ictaluri infection. Pathogen-specific pattern and tissue-specific pattern were found in the two infections. The significantly regulated expressions of catfish Hsp70 genes after bacterial infections suggested their involvement in immune response in catfish. [ABSTRACT FROM AUTHOR]

Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. In this study, through thorough data mining of existed channel catfish genomic resources, we identified a complete set of 15 septin genes. Septins were classified into four subgroups according to phylogenetic analysis. Extensive comparative genomic analysis, including domain and syntenic analysis, supported their annotation and orthologies. The expression patterns of septins in channel catfish were examined in healthy tissues and after infection with two major bacterial pathogens, Edwardsiella ictaluri and Flavobacterium columnare . In healthy channel catfish, most septin genes were ubiquitously expressed and presented diversity patterns in various tissues, especially mucosal tissues, proposing the significant roles septin genes may play in maintaining homeostasis and host immune response activities. After bacterial infections, most septin genes were regulated, but opposite direction in expression profiles were found with the two bacterial pathogens: the differentially expressed septin genes were down-regulated in the intestine after E. ictaluri infection while generally up-regulated in the gill after F. columnare infection, suggesting a pathogen-specific and tissue-specific pattern of regulation. Taken together, these results suggested that septin genes may play complex and important roles in the host immune responses to bacterial pathogens in channel catfish. [ABSTRACT FROM AUTHOR]

Background Although the short-term adverse effects of sorafenib are well known, few data exist on long-term toxicity. The objective of the present study was to investigate the prevalence of pancreatic atrophy among a cohort of patients with hepatocellular carcinoma (HCC) who were treated with sorafenib for ≥2 y. Methods Between March 2007 and December 2013, 31 patients with HCC who were treated with sorafenib for ≥2 y were identified. The effect of pancreatic atrophy and enhancement on incidence of adverse events, tumor response, and overall survival (OS) were assessed. Results Thirty-one patients with HCC were treated with sorafenib for ≥2 y and met inclusion criteria; 11 patients (35.5%) were Barcelona-clinic liver cancer stage B, whereas 20 patients (64.5%) were Barcelona-clinic liver cancer stage C. Median duration of treatment with sorafenib was 35.2 mo. Pancreatic atrophy and a decrease in pancreatic enhancement occurred in 24 patients (77.4%) and 15 patients (48.4%), respectively. On the basis of the modified response evaluation criteria in solid tumors, four patients (12.9%) had a complete response, 10 patients (32.3%) had a partial response, and 17 patients (54.8%) had stable disease. Patients treated with sorafenib with pancreatic atrophy had a median OS of 49.4 mo (95% confidence interval, 41.2–57.5 mo) compared with 31.2 mo (95% confidence interval, 25.7–36.7 mo) among patients who did not develop pancreatic atrophy ( P = 0.009). In contrast, survival was not associated with decreased versus normal enhancement of the pancreas (OS, 47.7 mo versus 41.7 mo, respectively; P = 0.739). Conclusions Pancreatic atrophy occurred in many HCC patients after 2 y of treatment with sorafenib. Patients who experienced pancreatic atrophy had a better tumor response and OS. [ABSTRACT FROM AUTHOR]

Despite similar histologic appearance amongst high-grade serous ovarian cancers (HGSOC), anecdotally there are differences in gross appearance. However, no systematic framework to classify morphologic differences exists. Therefore, we aimed to determine whether high-grade serous ovarian cancers (HGSOC) can be reliably divided into distinct gross morphologic subtypes and to assess clinical outcomes and molecular features of these subtypes. A retrospective review was performed of video-recordings from patients who underwent laparoscopic assessment of disease burden prior to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). Video recordings were reviewed by at least 2 physicians. A total of 4 sites (diaphragm, omentum, peritoneum, and pelvis) were assessed and classified as type I (deep, infiltrative disease with distortion of surrounding tissue) or type II (superficial, exophytic disease bordered by normal tissue). Tumor tissues from 16 of these chemotherapy-naïve patients were analyzed by multi-platform omics (RNA sequencing, proteomics). Clinical outcomes were assessed utilizing a prospectively collected database and compared by morphology using t-test or Fisher's exact test. Of the 99 evaluable patients, 60 exhibited uniform morphology at all involved metastatic sites (65% type I and 35% type II), and 81 exhibited a predominating morphology (58% type I and 42% type II). A total of 164 images were reviewed by a third physician with 83.5% inter-rater concordance (κ=0.6446). Patients with uniform type 1 (n=34)tumor morphology were more likely to exhibit an excellent response to NACT (defined as radiologic or CA-125 complete response) than those with type II (n=16) tumor morphology (47% vs 18%, p=0.13). Patients with type II predominant tumor morphology had a significantly higher estimated blood loss at the time of interval debulking surgery (p=0.008) as well as longer operative time (p=0.03) compared with type I tumor morphology. Patients with complete type II morphology were more likely to have a modified Fagotti score of <8 (p=0.026), and thus were more likely to be triaged to PDS. On histopathologic review of 7 type I cases and 4 type II cases, no obvious histo-pathological pattern dominated either type. We identified distinct molecular differences between the 2 types, including increased TGF-β expression in type I and increased MYC expression in type II. Type I tumors seem to have abundant stroma and are immunologically active, whereas type II tumors seem to be dominated by cancer cells, have little stroma, and are immunologically cold. There are at least two distinct gross morphological patterns of HGSOC with unique molecular differences and responses to chemotherapy. These findings could have major clinical implications for tailored therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Advanced high-throughput screening methods for small molecules may have important applications in the metabolic engineering of the biosynthetic pathways of these molecules. Ectoine is an excellent osmoprotectant that has been widely used in cosmetics. In this study, the Escherichia coli regulatory protein AraC was engineered to recognize ectoine as its non-natural effector and to activate transcription upon ectoine binding. As an endogenous reporter of ectoine, the mutated AraC protein was successfully incorporated into high-throughput screening of ectoine hyper-producing strains. The ectoine biosynthetic cluster from Halomonas elongata was cloned into E. coli . By engineering the rate-limiting enzyme l -2,4-diaminobutyric acid (DABA) aminotransferase (EctB), ectoine production and the specific activity of the EctB mutant were increased. Thus, these results demonstrated the effectiveness of engineering regulatory proteins into sensitive and rapid screening tools for small molecules and highlighted the importance and efficacy of directed evolution strategies applied to the engineering of genetic components for yield improvement in the biosynthesis of small molecules. [ABSTRACT FROM AUTHOR]

Abstract: Four cationic porphyrin–anthraquinone (Por–AQ) hybrids differing in lengths of flexible alkyl linkage, 5-[4-(1-N-anthraquinonon-yl)-l-oxophenyl]-10,15,20-tris(N-methylpyridinium-4-yl)porphyrin triiodide, (l =acetyl, pentanoyl, octanoyl, undecanoyl, designed as [AQATMPyP]I3, [AQPTMPyP]I3, [AQOTMPyP]I3 and [AQUTMPyP]I3, respectively, see Fig. 1), were synthesized and their interactions with DNA were investigated. The results of spectroscopic, denaturation and viscosity measurements suggest that [AQATMPyP]I3 binds to DNA through non-intercalative mode while the other three hybrids with longer links bind via bis-intercalative mode. Ethidium bromide (EB) competition experiment was carried out to determine the binding constants (K b) of these compounds for CT DNA, and [AQPTMPyP]I3 shows the largest K b among these hybrids. The photocleavage mechanism and wavelength-dependent cleaving abilities of these hybrids to pBR322 plasmid DNA were also comparably investigated. [Copyright &y& Elsevier]

Abstract: The reaction of lanthanide nitrate with 1,4-di (N,N-diisopropylacetamido)-2,3(1H,4H)-quinoxalinedione (L) yields six novel Ln(III) complexes ([Ln2L2(NO3)6(H2O)2]·H2O) which are characterized by elemental analysis, thermogravimetric analysis (TGA), conductivity measurements, IR, electronic and 1H NMR spectroscopies. A new quinoxalinedione-based ligand is used as antenna ligand to sensitize the emission of lanthanide cations. The lowest triplet state energy level of the ligand in the nitrate complex matches better to the resonance level of Eu(III) and Sm(III) than Tb(III) and Dy(III) ion. The f–f fluorescence is induced in the Eu3+ and Sm3+ complexes by exciting into the π–π* absorptions of the ligand in the UV. Furthermore, the crystal structures of a novel binuclear complex [Nd2L2(NO3)6(H2O)2]·H2O has been determined by single-crystal X-ray diffraction. The binuclear [Nd2L2(NO3)6(H2O)2]·H2O complex units are linked by the intermolecular hydrogen bonds and π–π interactions to form a two-dimensional (2-D) layer supramolecule. [Copyright &y& Elsevier]

Previous studies have shown that oxysterol binding protein like 2 (OSBPL2) knockdown is closely related to cholesterol metabolism. However, whether there is a direct relation between OSBPL2 and cholesterol synthesis is unknown. This study explored the mechanism of OSBPL2 deficiency in the upregulation of squalene epoxidase (SQLE) and the subsequent accumulation of intracellular cholesterol and cholesteryl ester. Here, we constructed an OSBPL2 -deleted HeLa cell line using CRISPR/Cas9 technology, screened differentially expressed genes and examined the transcriptional regulation of SQLE using a dual-luciferase reporter gene. RNA-seq analysis showed that SQLE was upregulated significantly and the dual luciferase reporter gene assay revealed that two new functional transcription factor binding sites of Sp1 transcription factor (SP1) and sterol regulatory element-binding transcription factor 2 (SREBF2) in the SQLE promoter participated in the SQLE transcription and expression. In addition, we also observed that OSBPL2 deletion inhibited the AMPK signalling pathway and that the inhibition of AMPK signalling promoted SP1 and SREBF2 entry into the nuclear to upregulate SQLE expression. Therefore, these data support that OSBPL2 deficiency upregulates SQLE expression and increases the accumulation of cholesterol and cholesteryl ester by suppressing AMPK signalling, which provides new evidence of the connection between OSBPL2 and cholesterol synthesis. OSBPL2 deletion upregulated SQLE expression and increased cholesterol synthesis in HeLa cells. Two new transcription factors binding site of SP1 and SREBF2 in human SQLE promoter were identified, and OSBPL2 deletion regulated nuclear translocation of SP1 and SREBF2 by inhibited the AMPK signaling pathway to elevate SQLE expression. Image 1 [ABSTRACT FROM AUTHOR]