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• Identification of DHSs can help to understanding the mechanism of disease development and the treatment of the disease. • Multi-dimensional feature fusion strategy was used for feature extraction from DNase samples. • An overall prediction accuracy of 0.859 was achieved with an AUC value of 0.837. DNase I hypersensitive sites (DHSs) are chromatin regions highly sensitive to DNase I enzymes. Studying DHSs is crucial for understanding complex transcriptional regulation mechanisms and localizing cis -regulatory elements (CREs). Numerous studies have indicated that disease-related loci are often enriched in DHSs regions, underscoring the importance of identifying DHSs. Although wet experiments exist for DHSs identification, they are often labor-intensive. Therefore, there is a strong need to develop computational methods for this purpose. In this study, we used experimental data to construct a benchmark dataset. Seven feature extraction methods were employed to capture information about human DHSs. The F -score was applied to filter the features. By comparing the prediction performance of various classification algorithms through five-fold cross-validation, random forest was proposed to perform the final model construction. The model could produce an overall prediction accuracy of 0.859 with an AUC value of 0.837. We hope that this model can assist scholars conducting DNase research in identifying these sites. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common bone malignant tumor. However, the genetic basis of OS pathogenesis is still not understood, and occurrence of chemo-resistance is a major reason for the high morbidity of OS patients. Recently, chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) has been identified as a gene related to malignant tumor progression. Unfortunately, its effects on OS development and drug resistance are still not understood. In the study, we attempted to investigate the effects of CHD1L on tumorigenesis and chemoresistance in OS. We found that CHD1L expression was markedly up-regulated in OS samples, especially in cisplatin (cDDP)-resistant patients. We also showed that OS cells with CHD1L knockdown were more sensitive to cDDP treatment with lower IC 50 values. In addition, we found that CHD1L deletion markedly reduced cell proliferation and induced apoptosis in OS cells with cDDP resistance. Moreover, the properties of cancer stem cells were highly suppressed in cDDP-resistant OS cells following CHD1L knockdown. Furthermore, multidrug resistance protein 1 (MDR-1) expression levels were dramatically decreased in OS cells with cDDP resistance when CHD1L was suppressed. Functional analysis indicated that CHD1L knockdown clearly restrained the activation of ERK1/2, protein kinase B (AKT) and NF-κB signaling pathways in cDDP-resistant OS cells. Consistently, animal experiments suggested that CHD1L suppression mitigated cDDP resistance in the generated in vivo xenografts. Collectively, CHD1L could modulate chemoresistance of OS cells to cDDP, and thus may be inspiring findings for overcoming drug resistance in OS. • CHD1L expression is increased in osteosarcoma and in cDDP-resistant patients. • CHD1L inhibition induces apoptosis and represses cancer stem like properties in osteosarcoma in vitro. • CHD1L knockdown reduces MDR-1, p-ERK1/2, p-AKT and p-NF-κB signals in drug-resistant osteosarcoma cells. • CHD1L suppression alleviates cDDP resistance in osteosarcoma in vivo. [ABSTRACT FROM AUTHOR]

Antioxidant defense is essential for animals to cope with homeostasis disruption during hibernation. The present study aimed to investigate the antioxidant defense response of juvenile soft-shelled turtle Pelodiscus sinensis during hibernation and following arousal. Turtle brain, liver, and kidney samples were collected at pre-hibernation (17 °C mud temperature; MT), during hibernation (5.8 °C MT) and after arousal (20.1 °C MT) in the field. Transcript levels of NF-E2-related factor 2 (Nrf2) decreased significantly during hibernation and recovered after arousal in all tissues. Cerebral and nephric copper-zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT), glutathione peroxidase 3 (GPx3) and nephric GPx4 mRNA showed similar changing patterns as Nrf2. Cerebral Mn SOD , GPx1 and nephric GPx1 up-regulated after arousal. Hepatic Cu/Zn SOD , GPx1 and GPx3 mRNA kept stable, except hepatic GPx4 increased during hibernation. Hepatic Mn SOD and CAT increased after arousal. In the GSH system, mRNA levels of glutathione synthetases (GS s) kept stable during hibernation and up-regulated after arousal in most tissues except nephric GS2 mRNA remained unchanged. Gene expressions of glutathione reductase (GR) exhibited a tissue specific changing pattern, while those of glutathione-S-Transferase (GST) shared a similar pattern among tissues: remained stable or down-regulated during hibernation then recovered in arousal. In contrast to these diverse responses in gene expressions, most of the antioxidant enzyme activities maintained high and stable. Overall, no preparation for oxidative stress (POS) strategy was found in enzymatic antioxidant system in P. sinensis juveniles during hibernation, the Chinese soft-shelled turtles were able to stay safe from potential oxidative stress during hibernation by maintaining high level activities/concentrations of the antioxidant enzymes/antioxidants. [ABSTRACT FROM AUTHOR]

The mismatch between urban transportation demands and local transportation supplies in municipal regions may cause serious traffic congestion and high vehicle exhaust emissions (VEEs). Although it has been found that road expansion and the provision of road public transport can mitigate traffic congestion and VEEs, the effectiveness of these public strategies in alleviating traffic congestion-related VEEs has been empirically compared in few studies. With the use of a panel dataset for 260 prefecture-level cities in China from 2013 to 2018, we fill this gap via empirically examining the effects of several popular strategies that promote the efficiency of urban road transportation, including road expansion and road public transport provision, on urban air pollution of fine particulate matter (PM 2.5). Then we further investigate metrics measured by passenger and freight volumes based on local urban road coverage that can suitably reflect the mismatch degree between local transportation demands and supplies. The empirical results indicated a positive and statistically significant correlation between urban PM 2.5 levels and road expansion but not between PM 2.5 levels and road public transport, suggesting that road expansion may unintentionally increase the transportation volume and thus local PM 2.5 levels. Importantly, we found that the passenger and freight volumes per unit road length are negatively and significantly correlated with the local particulate pollution concentration across different model specifications, while the passenger and freight volumes of road transportation do not directly affect local PM 2.5 levels. We also employed a series of robustness tests to overcome the concerns associated with measurement errors, omitted variable biases, model misspecifications and endogeneity, and consistent results were obtained. These results indicated that when facing limited public budgets, the passenger and freight volumes per unit road length should be considered to measure the effectiveness of road infrastructure investments in alleviating local particulate pollution caused by traffic congestion. • Several strategies for controlling urban PM2.5 from traffic are empirically compared. • Urban PM 2.5 levels are positively correlated with road expansion. • Urban PM 2.5 levels are not correlated with the provision of road public transport. • Transportation volumes with road coverage measure the transport efficiency. [ABSTRACT FROM AUTHOR]

Abstract The retina is the light sensing tissue of the eye which contains multiple layers of cells required for the detection and transmission of a visual signal. Loss of the light-sensing photoreceptors leads to defects in visual function and blindness. Previously, we found that mosaic deletion of Kcnj13, and subsequent loss of the potassium channel Kir7.1, in mice leads to photoreceptor degeneration and recapitulates the human retinal disease phenotype (Zhong et al., 2015). Kcnj13 expression in the retinal pigment epithelium (RPE) is essential for normal retinal electrophysiology, function, and survival. Mice with homozygous loss of Kcnj13 die at postnatal day 1 (P1), requiring a tissue-specific approach to study retinal degeneration phenotypes in adult mice. We used the CRISPR-Cas9 system to generate a floxed, conditional loss-of-function (cKO) Kcnj13 flox allele to study the pathogenesis of Kcnj13 deficiency in the retina. To investigate if the Kcnj13 is required in the RPE for photoreceptor function and survival, we used Best1-cre , which is specifically expressed in the RPE. We observed complete loss of Kcnj13 expression in Cre-positive RPE cells. Furthermore, our findings show that widespread loss of Kcnj13 in the RPE leads to severe and progressive thinning of the outer nuclear layer and a reduced response to light. Finally, to detect Best1-cre expression in the RPE of live animals without sacrificing the animal for histology, we generated a Cre-reporter-containing Kcnj13 cKO mouse line (cKOR: Kcnj13 flox/flox ; Best1-cre; Ai9) which can be rapidly screened using retinal fluorescence microscopy. These findings provide new tools for studying the roles of Kcnj13 in retinal homeostasis. Highlights • RPE-specific loss of Kcnj13 results in photoreceptor dysfunction and death. • Visual defects in RPE-specific loss of Kcnj13 animals coincide with progressive retinal degeneration. • RPE-specific Cre expression can be evaluated in living Kcnj13 cKOR mice using retinal fluorescence microscopy. [ABSTRACT FROM AUTHOR]

In this paper, we study minimal submanifolds in some general ( α , β ) -spaces. We firstly establish the equations for minimal submanifolds in a general ( α , β ) -space. Then we construct some kinds of minimal surfaces in some 4-dimensional general ( α , β ) -space. [ABSTRACT FROM AUTHOR]

[Display omitted] Transition metal oxides (TMOs) have received significant consideration. Because of their enormous theoretical capacity, cheap, and less toxicity. Notably, cobalt-based materials hold promises as negative electrode materials for batteries, but they suffer from less electrical conductivity and significant volume changes during operation. In order to address these challenges, sacrificial templating techniques at the nanoscale offer a potential solution for improving the electrochemical stability and rate performance of these materials. More specifically, these tactics have proven popular for designing Li-ion storages. To ascertain the impact of multiple metal ions on the electrochemical capacity, metal organic frameworks (MOFs) derived MCo 2 O 4 -MOF (M = Zn, Ni, Cu) were developed. Among these, ZnCo 2 O 4 showed the best electrochemical performance (927.2 mAh g-1 at 0.1 A g-1 after 250 cycles). Furthermore, calculations based on density functional theory (DFT) revealed that ZnCo 2 O 4 had the lowest Li+ adsorption energy, with a minimum value of −1.61 eV. Moreover, this research aims to design controllable nanostructures in order to enhance the design of transition bimetallic oxide composites for energy storage applications. [ABSTRACT FROM AUTHOR]

A new technology from Quanterix called SiMoA (single molecule array) which employs a fully automated system capable of ultrasensitive sandwich based ELISA detection was explored. Our studies focused upon the inhibition of the autophagy initiating kinase ULK1 by measuring the both total Atg13 and the phosphorylation of Atg13(pSer 318 ) from control and following compound treatment in either overexpressing or wild type tissue culture samples. The results show linear protein concentration dependence over two orders of magnitude and provide an assay window of 8- to 100-fold signal to background for inhibition of phosphorylation for both wild type and overexpressed samples, respectively. Moreover, overexpressed samples displayed 17-fold pSer 318 -Atg13 above wild type levels of with no apparent differences in compound potency. Lastly, the inhibition of ULK1 from mouse derived wild type xenografts also demonstrated loss of pSer 318 -Atg13 upon ULK1 inhibitor treatment that compared favorably to Western blot. These results show that the SiMoA technology can detect quantitatively low levels of endogenous biomarkers with the ability to detect the loss of pSer 318 -Atg13 upon ULK1 inhibition. [ABSTRACT FROM AUTHOR]

The underlying mechanism of gemcitabine resistance during breast cancer treatment remains unclear. Glucose regulated protein 78 (GRP78) frequently triggered by anticancer agents, was substantially elevated in gemcitabine resistant sublines. Ectopic expression of GRP78 changes gemcitabine chemosensitivity and apoptosis levels in breast cancer cells. Further experiments showed an involvement of caspase 9, not caspase 8, in gemcitabine resistance and GRP78-mediated chemosensitivity, suggesting that mitochondria apoptotic pathway was activated by GRP78. This finding was further supported by the observations of AKT activation, Bcl-2 increase, Bax and Bim decrease. Conclusively, GRP78 plays a vital role in gemcitabine resistance and clinical strategy to improve gemcitabine efficacy in breast cancer by manipulating GRP78 should be explored. [ABSTRACT FROM AUTHOR]

A new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway in plants. The structures of CPD analogues were characterized by 1H NMR and HRMS. The structure of N,N′ -bis(4-(tert-butyl)phenyl)cyclopropane-1,1-dicarboxamide was further elucidated by X-ray diffraction. The herbicidal activities of these compounds were tested against lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). Most of these compounds exhibited low herbicidal activity against both plant species. Among them, N,N′ -bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide displayed moderate activity against bentgrass. Inhibition of KARI activity by the CPD analogues was also assessed experimentally and by molecular docking simulation with results supporting inhibition of KARI as their mode of action. These results provide the basis for design of more effective KARI inhibitors. A series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI). Their structures were confirmed by NMR, HRMS and X-ray diffraction. The KARI activity and herbicidal activity results indicated that some of them exhibited good activity. The mode of action was studied by using molecular docking. The SAR was also studied. [Display omitted] • The new cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. • The herbicidal and KARI activity were examined with new CPD analogues and structure-activity relationship was studied. • The molecular property, molecular docking and ADMET prediction were done. [ABSTRACT FROM AUTHOR]

To reveal SUMOylation and the roles of Sentrin-specific proteases (SENP)s in microglial cells under Intermittent hypoxia (IH) condition would provide more intensive view of understanding the mechanisms of IH-induced central nervous system (CNS) damage. Hence, in the present study, we detected the expression levels of SENPs in microglial cells under IH and normoxia conditions via RT-PCR assay. We found that SENP1 was significantly down-regulated in cells exposure to IH. Subsequently, the effect of IH for the activation of microglia and the potential roles of SENP1 in the SENP1-overexpressing cell lines were investigated via Western blotting, RT-PCR and Griess assay. The present study demonstrated the apoptosis-inducing and activating role of IH on microglia. In addition, we revealed that the effect of IH on BV-2 including apoptosis, nitric oxide synthase (iNOS) expression and nitric oxide (NO) induction can be attenuated by SENP1 overexpression. The results of the present study are of both theoretical and therapeutic significance to explore the potential roles of SENP1 under IH condition and elucidated the mechanisms underlying microglial survival and activation. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-612 suppresses tumorsphere and clone formation of HCC cells. [•] miR-612 reduces drug resistance of HCC cells. [•] miR-612 suppresses tumorigenesis of HCC in NOD/SCID mice. [•] miR-612 inhibits an invasive frontier of HCC xenografts. [•] miR-612 suppresses Wnt/β-catenin signaling. [Copyright &y& Elsevier]

Abstract: Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored. MLN4924 acts as a substrate-assisted inhibitor of NAE by forming a tight binding Nedd8–MLN4924 adduct. The inhibited enzyme can no longer transfer Nedd8 downstream to modify and activate the E3 cullin–RING ligases. This results in the stabilization of proteins regulated by the proteasome, leading to cell death. These studies monitored the endogenous cellular changes to NAE∼Nedd8 thioester, the formation of the Nedd8–MLN4924 adduct, and the reduction in the Cul1–Nedd8. Lysates derived from MLN4924-treated HCT116 cells showed that whereas the β-subunit of NAE remained constant, reductions of both NAE∼Nedd8 thioester and Cul1–Nedd8 levels occurred with a concomitant rise of the adduct. Moreover, the formation of the Nedd8–MLN4924 adduct was approximately stoichiometric with the concentration of NAEβ. Higher density 384-well cell-based assays illustrated the kinetics of enzyme inactivation across a wider range of MLN4924 concentrations, showing a rapid loss of NAE∼Nedd8 thioester and Cul1–Nedd8. The reduction of NAE∼Nedd8 thioester precedes the loss of Cul1–Nedd8 at twice the rate. Finally, these results clearly demonstrate the utility of the homogeneous assay for quantitative assessment of these endogenous cellular components in a 384-well plate in response to inhibition of NAE by MLN4924. [Copyright &y& Elsevier]

Abstract: In this paper we study the structure of tangent bundle of a Riemannian manifold with a general metric . We prove that is flat if and only if it is Kählerian, and is Kählerian if and only if it is almost Kählerian and is flat. We also prove that Einstein if and only if both and are flat. Finally, for to be a space form with constant curvature, we obtain a necessary and sufficient condition for having the constant scalar curvature. [Copyright &y& Elsevier]

Abstract: We prove that the Ohno–Zagier relation of multiple zeta values can be deduced from the regularized double shuffle relation. At the same time, we provide an algebraic proof of Ohno–Zagier relation. [Copyright &y& Elsevier]

Abstract: Individuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that associates with polyribosomes and negatively regulates translation. In a previous study of a mouse model of FXS (Fmr1 knockout (KO)) we demonstrated that in vivo rates of cerebral protein synthesis (rCPS) were elevated in selective brain regions suggesting that the absence of FMRP in FXS may result in dysregulation of cerebral protein synthesis. Lithium, a drug used clinically to treat bipolar disorder, has been used to improve mood dysregulation in individuals with FXS. We reported previously that in the Fmr1 KO mouse chronic dietary lithium treatment reversed or ameliorated both behavioral and morphological abnormalities. Herein we report that chronic dietary lithium treatment reversed the increased rCPS in Fmr1 KO mice with little effect on wild type mice. We also report our results of analyses of key signaling molecules involved in regulation of mRNA translation. Our analyses indicate that neither effects on the PI3K/Akt nor the MAPK/ERK 1/2 pathway fully account for the effects of lithium treatment on rCPS. Collectively our findings and those from other laboratories on the efficacy of lithium treatment in animal models support further studies in patients with FXS. [Copyright &y& Elsevier]

Abstract: Pharmacodynamic responses to drug treatment are often used to confirm drug-on-target biological responses. Methods ranging from mass spectrometry to immunohistochemistry exist for such analyses. By far, the most extensively used methodologies employ antigen-specific antibodies for detection (at a minimum) and, in some cases, target quantitation as well. Using a novel frequency-modulating technology from BioScale called acoustic micro magnetic particle (AMMP) detection, two pathway biomarkers were chosen for pharmacodynamic analysis and compared with either AlphaScreen or LI-COR Western blot assays. For these studies, pharmacodynamic biomarkers for both proteasome and phosphoinositol 3-kinase inhibition were used. Our results show clearly that the BioScale technology is a robust and rapid method for measuring recombinant standards or endogenously derived proteins from both tissue culture and mouse xenograft tumor lysates. Moreover, the sensitivity obtained with the BioScale platform compares favorably with LI-COR Western blot and AlphaScreen technologies. Furthermore, the use of the ViBE Bioanalyzer eliminates the labor-intensive effort of Western blot analysis and is devoid of the optical and other endogenous interfering substances derived from lysates of xenograft tumors typically observed with AlphaScreen. [ABSTRACT FROM AUTHOR]

Abstract: Spatial surfaces with parallel mean curvature vector in pseudo-Euclidean spaces of arbitrary dimension and index were classified by B.Y. Chen. In this work, we give a complete classification of Lorentzian surfaces with parallel mean curvature vector in pseudo-Euclidean spaces of arbitrary dimension and index. Consequently, the problem to classify all the surfaces with parallel mean curvature vector in pseudo-Euclidean spaces has been solved. [Copyright &y& Elsevier]

Abstract: Let be a field of characteristic 0, and R be a commutative -algebra. Let be an element in with regularized double shuffle relations. We define a gamma series associated to Φ. We prove that the associated beta series is just the image of in the commutative formal power series ring , where if , then . We also give some equivalent conditions for the reflection formula of the gamma series . [Copyright &y& Elsevier]

Abstract: A well-known classical result classifies the surfaces in 3-space with the mean curvatures H and the Gauss curvatures K satisfying as pieces of planes or two spheres. Corresponding results are given here for Lorentzian surfaces in Minkowski 3-space. This work is done by proving that all the Lorentzian surfaces with in Minkowski 3-space are null scrolls locally and can be classified into three cases, two of which have no counterparts in Euclidean space. [Copyright &y& Elsevier]

Abstract: In this paper, we prove that any helicoidal surface with in Minkowski 3-space is locally a generalized umbilical surface, i.e., a surface with the shape operator having the minimal polynomial , where a is constant. We also give the representation formulas for these helicoidal surfaces. [Copyright &y& Elsevier]

Abstract: E1 and E2 glycoproteins are structural components of hepatitis C virus (HCV) virion. They are involved in cellular receptors interaction, neutralising antibodies elicitation, and viral morphogenesis. They are considered as major candidates for anti-HCV vaccine. In this report, we first expressed tandem E1E2 as well as C-terminally truncated E1 fragment and C-terminally truncated E2 fragment, respectively, in Escherichia coli cells and the proteins were purified to homogenesis. All the purified proteins can react specifically with patient sera. Both purified chimeric protein E1E2 and protein E2 can interact with a putative cellular receptor CD81, while purified protein E1 cannot interact with CD81. The sera of rabbit immunized with the E1E2 inhibited the binding of E2 protein to the major extracellular loop of human CD81 and reacted with both proteins E1 and E2, respectively. Anti-E1 and E2 antibodies can be generated simultaneously in the rabbit immunized with the E1E2, and the titers of antibodies were 63 or 56% higher than the titers induced by E1 or E2 alone, respectively. The results suggest that E1 and E2 can enhance their immunogenicity each other in chimeric protein E1E2 and the E. coli-derived chimeric protein E1E2 and corresponding antisera can be used as an useful tools in anti-HCV vaccine research. [Copyright &y& Elsevier]

Abstract: In this paper, we construct helicoidal surfaces under the cubic screw motion with prescribed mean or Gauss curvature in Minkowski 3-space . We also find explicitly the relation between the mean curvature and Gauss curvature of them. Furthermore, we discuss helicoidal surfaces under the cubic screw motion with and prove that these surfaces have equal constant principal curvatures. [Copyright &y& Elsevier]

Abstract: In this paper we constructed a helicoidal surface with a light-like axis with prescribed mean curvature or Gauss curvature given by smooth function in 3-dimensional Minkowski space and solved an open problem left by Beneki, Kaimakamis, and Papantoniou in [J. Math. Anal. Appl. 275 (2002) 586–614]. [Copyright &y& Elsevier]

Angiotensin-converting enzyme 2 (ACE2 or ACEH) is a novel angiotensin-converting enzyme-related carboxypeptidase that cleaves a single amino acid from angiotensin I, des-Arg bradykinin, and many other bioactive peptides. Using des-Arg bradykinin as a template, we designed a series of intramolecularly quenched fluorogenic peptide substrates for ACE2. The general structure of the substrates was F-X-Q, in which F was the fluorescent group, Abz, Q was the quenching group (either Phe(NO2) or Tyr(NO2)), and X was the intervening peptide. These substrates were selectively cleaved by recombinant human ACE2, as shown by MS and HPLC. Quenching efficiency increased as the peptide sequence was shortened from 8 to 3 aa, and also when Tyr(NO2) was used as a quenching group instead of Phe(NO2). Two of the optimized substrates, TBC5180 and TBC5182, produced a signal:noise ratio of better than 20 when hydrolyzed by ACE2. Kinetic measurements with ACE2 were as follows: TBC5180, Km=58 μM and kcat/Km=1.3×105 M−1 s−1; TBC5182, Km=23 μM and kcat/Km=3.5×104 M−1 s−1. Thus, based on hydrolysis rate, TBC5180 was a better substrate than TBC5182. However, TBC5180 was also hydrolyzed by ACE, whereas TBC5182 was not cleaved, suggesting that TBC5182 was a selective for ACE2. We conclude that these two peptides can be used as fluorescent substrates for high-throughput screening for selective inhibitors of ACE2 enzyme. [Copyright &y& Elsevier]

Previous studies consider the installment cost of environmental practices and farming yield loss as the basis for incentive payment in environmental programs. This study introduces two additional dimensions. We first demonstrate that the incentive payment is also determined by opportunity wages from non-farming activities. Second, we show that in addition to individual farm characteristics, community characteristics also play a role in determining the compensation required by farmers to adopt environmental practices. The empirical analysis examines these factors by using survey data on farmers' water quality improving practices combined with several publicly available data sources on non-farming wages from selected industries, as well as characteristics of the community the farmers are located in. Findings suggest that opportunity wages from non-farming activities have significant positive effects on compensation required thus on environmental practice adoption. Community characteristics such as community wealth and resident composition can also influence adoption decisions. Additional abatement of nonpoint source pollution is unlikely to be accomplished if the incentive payment does not consider non-farming incomes and characteristics of the local community. • We demonstrate and explicitly examine that the incentive payment is also determined by opportunity wages from non-farming activities. Past studies on adoption of environmental technologies have tended to include only oblique proxies, such as non-farm or household income. • We show that in addition to individual farm characteristics, community characteristics also play a role in determining the compensation required by farmers to adopt environmental practices. Community traits, such as wealth and demographic profile, have rarely been incorporated into environmental practice adoption models. • We develop a theoretical framework illustrating factors determining incentive payment. [ABSTRACT FROM AUTHOR]

The initial boundary value problems for compressible Navier-Stokes-Poisson and Euler-Poisson equations of plasma are considered on exterior domains in this paper. With the radial symmetry assumption, the global existence of solutions to compressible Navier-Stokes-Poisson equations with the large initial data on a domain exterior to a ball in R n (n ≥ 1) is proved. Moreover, without any symmetry assumption, the global existence of smooth solutions near a given constant steady state for both compressible Navier-Stokes-Poisson and Euler-Poisson equations on an exterior domain in R 3 with physical boundary conditions is also established with the exponential stability. A key issue addressed in this paper is on the global-in-time regularity of solutions near physical boundaries. This is in particular so for the 3-D compressible Navier-Stokes-Poisson equations to which global smooth solutions of initial boundary value problems are seldom found in literature to the best of knowledge. [ABSTRACT FROM AUTHOR]

[Display omitted] The p-i heterojunction imbedded underneath the perovskite layer plays a vital role in determining the efficiency and stability of inverted perovskite solar cells (PSCs). We found that poly[bis(4-phenyl) (2,4,6-trimethylphenyl) amine] (PTAA) suffers from the severely chain entanglement resulting in poor contact with perovskite. In this work, PTAA layer was treated by poly[(2,6-(4,8-bis(5-(2-ethylhexylthio)-4-fluorothiophen-2-yl)-benzo[1,2-b:4,5-b′] dithiophene))- alt -(5,5-(1′,3′-di-2-thienyl-5′,7′-bis(2-ethylhexyl) benzo[1′,2′-c:4′,5′-c′] dithiophene-4,8-dione)] (PBDB- T -SF) diluted solution in chlorobenzene. PBDB- T -SF, which contains dual carbonyl groups in its backbones and suitable electronic levels, can spontaneously fill the voids in chlorobenzene-washed PTAA (nano-PTAA). This not only promotes the work function of the substrate but also strengthens the coherence between perovskite and the substrate. Blade coated PSC (0.09 cm2) containing PBDB- T -SF (s-PSCs) realized a power conversion efficiency (PCE) of 21.83 %. After aging for more than 2000 h, s-PSCs maintains 88 % of the initial efficiency which is only 59 % for the control devices. [ABSTRACT FROM AUTHOR]

Abstract Although Myriophyllum aquaticum exhibits efficient nitrogen and phosphorus removal from wastewater, it has poor performance on organic matter removal. Here, a wastewater treatment system combining M. aquaticum and activated sludge was developed to improve its removal of organic matter. The Box–Behnken response surface methodology was used to optimize the construction conditions of the system, and the effects of time, temperature, illumination intensity, pollutant load, and dissolved oxygen (DO) on plant mass increment (PMI) and microbial biomass (MB) of the system were investigated. The wastewater remediation potential of the system was then evaluated. The results show that temperature and illumination intensity significantly affected PMI (p < 0.01), and that time, pollutant load, and DO were the most significant factors affecting MB (p < 0.01). The optimal construction conditions were 18.77 days in length, a temperature of 20.42 °C, an illumination intensity of 5827.61 Lx, a pollutant load of 120.61 mg/g plant, and a DO of 3.21 mg/L. The inoculation of activated sludge caused MB of the system to increase by four times relative to the non-inoculated system, suggesting successful formation of biofilms on M. aquaticum. Additionally, the removal of chemical oxygen demand (COD) from wastewater was significantly enhanced by the combined approach compared with a system relying solely on M. aquaticum. This study provides a new method for improving the remediation efficiency of M. aquaticum by combining the use of this species and activated sludge. Highlights • A system was constructed by the combined use of M. aquaticum and activated sludge. • Response surface methodology was used for optimizing system conditions. • Biofilm attached onto was successfully M. aquaticum formed. • Organic matter removal potential by the system was significantly enhanced. [ABSTRACT FROM AUTHOR]

The Macrobrachium rosenbergii industry is threatened by various Aeromonas , resulting in high mortality of adult prawns. However, there are few studies on the immune response of M. rosenbergii infected with Aeromonas dhakensis. In this study, we observed the hepatopancreas and gills histopathologically, performed a comparative transcriptome analysis of the hepatopancreas, and analyzed the candidate gene expression of immune-related genes in the hemolymph, hepatopancreas, and gills of M. rosenbergii that had been infected with A. dhakensis. Histopathology revealed the hepatopancreas was successively inflamed, followed by cellular vacuolation, lumen deformation, and finally tissue erosion; partial and severe inflammation of the gills occurred successively, and eventually the gill tissue atrophy and the gill filaments detached from the gill arch. Transcriptome analysis showed that a total of 77,742 unigenes and 8664 differentially expressed genes (DEGs), and the immune-related DEGs were mainly enriched in lysosome and phagosome pathways. In addition, 4 immune-related candidate genes (RhoA, CASP9, PKC, and DSCIGN) based on KEGG and PPI analysis were monitored at 6, 12, and 24h post injection (hpi) in hepatopancreas, hemolymph and gills. Their spatio-temporal expression results indicated that A. dhakensis have activated the immune system of M. rosenbergii. The present study may provide new information on the complex immune mechanism of M. rosenbergii. • It was the first report on the immune response of Macrobrachium rosenbergii infected with Aeromonas dhakensis. • The tissures of M. rosenbergii in the challenge group had various degrees of damage. • The candidate immune-related genes (Casp9 , PKC , RhoA , and DCSIGN) actively participated in immune activities. [ABSTRACT FROM AUTHOR]

• There is an increasing trend to develop environmentally friendly and affordable biopesticides across the globe. • Microbial agents represent 60 % of the biopesticide market but only 3 % of the global pesticide market. • Paenibacillus elgii , Pseudomonas spp., Aspergillus spp. and Cladosporum spp. are novel microbial biopesticides. • Combinations of microbial agents with beneficial predators are promising strategies for pest control in protected cropping. • Formulations improvements are needed cost efficiency and broad-spectrum activity for commercial use in protected cropping. The increasing adoption of environmentally friendly agricultural pesticides can be attributed to the continuous development and optimisation of both strategies and availability of products for pest management. This aligns with the increase in global population, decline of arable land and health concerns about synthetic pesticides. One outcome has been the development of protected cropping for enhancing productivity and quality of horticultural products worldwide. In 2020, biopesticides represented 6 % of the global pesticide market, but their share is expected to double and reach nearly 15 % by 2031. Microbial products have been mainly based on a limited number of pathogenic species, including Bacillus thuringiensis , Beauveria bassiana and Metarizhium anisopliae. Here, we review the current progress of biopesticide products for agriculture. In particular, we explore opportunities to utilise entomopathogens in protected cropping (controlled environment agriculture), where they have several advantages for integrated pest management (IPM) in these systems. There are a range of candidate entomopathogens such as Paenibacillus elgii , Pseudomonas spp., Aspergillus spp. and Cladosporum spp. that may be employed as biological control agents (BCAs) in protected cropping. Furthermore, the use of endophytic entomopathogenic fungi (EPF) is a promising alternative strategy for IPM in protected cropping. Also, we review the future strategies for IPM in protected cropping systems, including the combination of different BCAs. We suggest that interactions between combinations of BCAs, particularly EPF-Entomopathogenic bacteria (EPB) and EPF-beneficial arthropods, can offer promising IPM strategies, providing opportunities towards sustainable food production in the future. [ABSTRACT FROM AUTHOR]

In this paper we consider the quasilinear chemotaxis system { u t = ∇ ⋅ ( D ( u ) ∇ u ) − χ ∇ ⋅ ( u ∇ v ) + f ( u ) , x ∈ Ω , t > 0 , 0 = Δ v − μ ( t ) + u , x ∈ Ω , t > 0 , with homogeneous Neumann boundary conditions in a bounded domain Ω ⊂ R n with n ≥ 2 , where χ > 0 , μ ( t ) : = 1 | Ω | ∫ Ω u ( x , t ) d x and f ∈ C ( [ 0 , ∞ ) ) ∩ C 1 ( ( 0 , ∞ ) ) is a logistic source of the form f ( s ) = a s − b s κ with a ≥ 0 , b > 0 , κ > 1 and s ≥ 0 , and the diffusion D ∈ C 2 ( [ 0 , ∞ ) ) is supposed to satisfy D ( s ) ≥ D 0 s − m for all s > 0 with some D 0 > 0 and m ∈ R . Given any b > 0 , when the logistic source is strong enough in the sense that κ > m + 3 − 4 n + 2 and κ > 2 , it is shown that for any initial data u 0 ∈ C 0 ( Ω ¯ ) and n ≥ 2 the problem possesses a unique global bounded classical solution. However, when D ( s ) = D 0 s − m for all s > 0 with 4 n − 1 < m ≤ 0 in the sense that n ≥ 5 , and the effect of logistic source is weaker in the sense that κ ∈ ( 1 , ( 3 − m ) n − 2 2 n − 2 ) , it is shown that for arbitrary prescribed M 0 > 0 there exists initial data u 0 ∈ C ∞ ( Ω ¯ ) satisfying ∫ Ω u 0 = M 0 such that the corresponding solution ( u , v ) of the system blows up in finite time in a ball Ω = B 0 ( R ) ⊂ R n with some R > 0 . This result extends the blow-up arguments of the Keller–Segel chemotaxis model with logistic cell kinetics in Winkler [39] to more general quasilinear case. Moreover, since there is a gap in the proof of Zheng et al. [46] , it also presents modified results for the mistake. [ABSTRACT FROM AUTHOR]

We report a new class of edge-centered photonic square lattices with multiple flat bands, and consider in detail two examples: the Lieb-5 and Lieb-7 lattices. In these lattices, there are 5 and 7 sites in the unit cell and in general, the number is restricted to odd integers. The number of flat bands m in the new Lieb lattices is related to the number of sites N in the unit cell by a simple formula m = ( N − 1 ) ∕ 2 . The flat bands reported here are independent of the pseudomagnetic field. The properties of lattices with even and odd number of flat bands are different. We consider the localization of light in such Lieb lattices. If the input beam excites the flat-band mode, it will not diffract during propagation, owing to the strong mode localization. In the Lieb-7 lattice, the beam will also oscillate during propagation and still not diffract. The period of oscillation is determined by the energy difference between the two flat bands. This study provides a new platform for investigating light trapping, photonic topological insulators, and pseudospin-mediated vortex generation. [ABSTRACT FROM AUTHOR]

[Display omitted] • The recent advances in the immobilization of enzymes based on hierarchical NFs was reviewed. • The application of enzymes-inorganic hNFs was summarized. • The information on metrics regarding catalytic performance of the enzymes-inorganic hNFs was comprehensive discussed. In general, enzyme immobilization technologies were applied for seeking to create reusable enzymes with improved enzyme properties for industrial applications. However, to traditional immobilization technologies, such as adsorption, covalent binding, cross-linking, and entrapment, the reusability and stability are improved, the activity is often obviously reduced compared with the free enzyme. To resolve this challenge, the recently appeared hierarchical Nanoflowers (NFs) technology opened a new door for enzyme immobilization, which possesses the inherent merits such as enhanced loading capacity and high specific surface area. Recent researches have clearly stated that it is an inexpensive and environmentally benign technology for enzyme immobilization. In this review, we focus on the recent advances in the immobilization of enzymes with the environmentally benign hierarchical NFs, as well as their application. [ABSTRACT FROM AUTHOR]

A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in autumn and spring from Harbin, a megacity in China, using GC-MS/MS base quantitative trace analysis. The results showed that a total of 33 pesticides were detected in road dust and green-belt soil, with the total concentrations of 650 and 236 ng/g (dry weight = dw), respectively. The concentrations of pesticides in road dust were significantly higher than that in green-belt soil. Pesticides in the environment were influenced by the seasons, with the highest concentrations of insecticides in autumn and the highest levels of herbicides in spring. In road dust, the concentrations of highways in autumn and spring (with the mean values of 94.1 and 68.2 ng/g dw) were much lower than that of the other road classes (arterial roads, sub-arterial roads and branch ways). Whereas in the green-belt soil, there was no significant difference in the concentration of pesticides between the different road classes. A first risk assessment was conducted to evaluate the potential adverse health effects of the pesticides, the results showed that the highest hazard index (HI) for a single pesticide in dust and soil was 0.12, the hazard index for children was higher than that for adults, with an overall hazard index of less than 1. Our results indicated that pesticide levels do not have a significant health impact on people. [Display omitted] • 33 pesticides were detected in road dust and green-belt soil in autumn and spring. • The concentration of pesticides in road dust was higher than in green-belt soil. • Compared to road classes, seasons had a more significant effect on concentrations. • The highest hazard index of pesticides was below 1, indicating a safety threshold. [ABSTRACT FROM AUTHOR]

The Central Plains of China is ideal for studying the interplay between agricultural production and social complexity. Focusing on four sites (Wangchenggang, Chengyao, Wadian, and Xinzhai) dating to the Late Longshan (2200–1900 BCE) in the Central Plains, the present study described species identification results of charred crop seeds at each site and then carried out carbon and nitrogen stable isotope analyses of 55 samples consisting of 456 cereal grains and soybeans. Our results suggest the different landforms were exploited in the Central Plains during the Late Longshan period, with foxtail millet (Setaria italica), common millet (Panicum miliaceum), rice (Oryza sativa), and soybean (Glycine max) being favorably cultivated in lands with different geographic features. We also propose the practice of millet and rice manure in the region. Furthermore, the inhabitants at centralized settlements such as Wadian seemed to have differed in their ability to procure and consume the better-manured millets and rice, an indication that crop foods and social status may be intertwined. While the implications of our isotopic study are constrained by the small sample size, our data are broadly compatible with the hypothesis that the diversified agricultural system contributes to the formation of institutionalized inequality. Further work and research directions are also highlighted. • Agriculture was key to the rise of early states in the Central Plains of China. • We report carbon and nitrogen stable isotopes for four key sites in the region. • We suggest that millet and rice were bettered manured. • The two millets, rice, and soybean were favorably planted in different landforms. • We also notice differential consumption of crops at centralized settlements. [ABSTRACT FROM AUTHOR]

Multi-factor risk assessment is an important prerequisite for water quality protection and the safe operation of mega hydro-projects. As the largest long-distance inter-basin water diversion project in the world, the Middle Route of the South-to-North Water Diversion Project of China (MRSNWDPC) has been in operation for 8 years and has benefited 79 million people along the canal. However, concerns have been raised in recent years about the potential negative effects of abnormal algal proliferation in the MRSNWDPC. It is very important for the safety of water supply to carry out relevant risk analysis and formulate regulatory management. In order to quantitatively evaluate the risk of algal proliferation in the MRSNWDPC under the influence of multiple factors, a multivariate risk assessment method based on Vine Copula theory and Monte Carlo simulation was proposed. Five key factors (water temperature, flow velocity, flow rate, algal cell density, and dissolved oxygen) were used and multiple dependency models in each section of the MRSNWDPC from January 2016 to January 2019 were established to study the risk of algal proliferation under multiple scenarios. The results demonstrate that water temperature can be used as an appropriate early-warning indicator of algal proliferation. The early-warning interval (unit: °C) of water temperature in the upper, middle, and lower reaches are 26–29°C, 23–26°C, and 21–23°C, respectively. Unlike bivariate analysis, the multiple dependency model describes the relationship between variables more accurately and enriches the scenarios of multiple conditional probabilities. When the water temperature fluctuates in the early-warning interval, regulating the upstream, midstream, and downstream flow velocity to be higher than 0.6 m/s, 0.5 m/s, and 0.6 m/s, respectively, can effectively reduce the risk of algal proliferation. This research not only provides a reference for the ecological control of algae in the MRSNWDPC and similar mega hydro-projects but also enriches the application of the Vine Copula theory coupled with the random sampling method for multi-variable risk analysis. [Display omitted] • ●The risk of algal proliferation under multiple scenarios is comprehensively analyzed. • Algal early-warning thresholds of water temperature and flow rate are determined. • The regulation strategy of algal control in water diversion project is proposed. • The Vine Copula-based Model is effectively applied in multi-scenario risk analysis. [ABSTRACT FROM AUTHOR]

Soil salinity is one of the major abiotic stresses, which negatively affects the productivity of plants in both cultivated and natural environments. Salinity stress increases osmotic stress and ROS accumulation and breaks the ionic balance in plant cells. In stomatal guard cells, these factors cause ABA biosynthesis and stomatal closure, resulting in the reduction of CO2 assimilation and crop yield loss. Halophytes are the plants capable to thrive in an extremely saline environment, thus consider as one of the vital resources for breeding salt-tolerant crops. Understanding the common and specific adaptive mechanisms to salinity of halophytes and glycophytes (most crop species) is one of the effective approaches to mining the salt tolerance-associated genetic resources. Here, we first reviewed the physiological traits conferring salinity tolerance traits (stomatal density, stomatal aperture, photosynthetic characteristics, and ion content) between halophytes and glycophytes. Comparative genomic and transcriptomic analysis of key membrane transporters regulating stomatal opening and closure is then conducted to explore the adaptation mechanisms of halophytes and glycophytes to salinity stress. In summary, future research is suggested to focus more on halophytes to gain a better mechanistic understanding of salt tolerance before applications in glycophytic crop breeding. [ABSTRACT FROM AUTHOR]

The Synthetic Aperture Focusing Technique (SAFT) is employed in laser ultrasonic non-destructive testing to image defects. However, during the laser ultrasonic imaging process, the influence of multi-mode waves often introduces various artifacts in the imaging results. We investigated a multi-iteration frequency-domain SAFT (MIF-SAFT) algorithm to tackle this challenge. Initially, a single low-precision F-SAFT imaging result is performed to identify potential defect locations. Subsequently, a back-projection method is applied to determine defect positions and separates acoustic waves of different modes in the B-scan. After that, a multi-mode F-SAFT imaging is performed for evaluation, and the above process is repeated until the imaging outcome stabilizes. The result shows that artifacts are removed when the image remains unchanged after multiple iterations, and the imaging quality is effectively improved by MIF-SAFT. Furthermore, including directivity patterns of laser ultrasound also enhances defect imaging capabilities within MIF-SAFT. Additionally, we examined the MIF-SAFT's capacity to detect multiple defects, which can image them simultaneously. • Multi-iteration in F-SAFT for artifact removal. • Different ultrasonic signals are separated by using the algorithm. • Directivity patterns are performed to enhance the imaging result. • Applied for multiple defects imaging simultaneously. [ABSTRACT FROM AUTHOR]

Abstract: The gene coding for the lipase-solubilized bovine liver microsomal cytochrome b 5 (cyt b 5) was expressed in Escherichia coli BL21 cells as a glutathione S-transferase fusion protein (GST-cyt b 5) using the constructed expression vector pGEX-cyt b 5. The GST-cyt b 5 fusion protein can be matured in vivo as a holoprotein with heme incorporated into cyt b 5 during the fermentation, and the purification procedures were simplified by using a one-step affinity column chromatography with glutathione–agarose gel. The fusion protein was characterized by its spectroscopic and electrochemical properties, the interaction between GST-cyt b 5 and cyt c was also investigated. The results show that GST-cyt b 5 fusion protein shares similar properties and functions to that of isolated cyt b 5. Although cyt b 5 and GST were fused together, the two partners have not made significant structural and functional alterations of their counterparts, the protein–protein interactions between them are apparently very weak. To our knowledge, the present study is the first report to express cyt b 5 as a GST-cyt b 5 fusion protein, which provides a good example for the in vivo maturation of a hemoprotein as a GST fusion protein and sheds new light on the protein–protein interactions within the GST fusion protein. [Copyright &y& Elsevier]

• WENO-K reduces dissipation and preserves high-resolution around discontinuities. • By optimizing hyper-parameters, the accuracy of reconstructions is improved. • Indicators are developed to identify troubled cells efficiently and precisely. • WENO-K is supposed to be well applied to other variants of WENO scheme. An adaptive finite-difference WENO method with Gauss-kriging reconstruction (we call it WENO-K) is proposed to reduce dissipation in smooth regions of flow while preserving high-resolution around discontinuities for hyperbolic system of conservation laws. The method adopts a kriging model with non-polynomial Gauss exponential function to obtain new reconstruction coefficients that contain a hyper-parameter. By adaptively optimizing the hyper-parameter and automatically identifying troubled cells using newly developed indicators, the accuracy in the smooth region is obviously improved. Compared with the classical WENO-JS method, the proposed WENO-K method provides more accurate reconstructions and sharper solution profiles near discontinuities. Furthermore, the WENO-K method is easy to implement in an existing classical WENO code with less than 13%–16% of additional computational cost. Numerical results demonstrate that the proposed method outperforms the WENO-JS method for a broad range of problems. This method is supposed to be applied to other variants of WENO scheme and offers the potential of improving their accuracy. [ABSTRACT FROM AUTHOR]

Water pollution caused by antibiotics and heavy metals has attracted considerable concern, and efficient approaches are urgently needed for their removal. The objective of this study was to investigate the potential of Myriophyllum aquaticum for long-term phytoremediation of wastewater containing tetracycline (TC) antibiotics and copper. Seven hydroponic microcosms were constructed, spiked with tetracycline, oxytetracycline (OTC) and chlortetracycline (CTC) (300–30,000 μg/L), alone or simultaneously with Cu (II), and operated for 12 weeks. The TC removal efficiencies using the hydroponic microcosms here were commensurate or higher than those in previous studies. However, the Cu/TC ratio greatly affected the removal, accumulation of TCs by M. aquaticum , and plant growth. Low levels of Cu (II) (<1000 μg/L) promoted TC removal, but excessive Cu (II) (>10,000 μg/L) impeded it. Mass balance analysis showed that most TCs (45%–64% on average) accumulated in the roots of M. aquaticum. Plant biomass was correlated with the removal of COD, TN, TP, and NH 4 +-N (p ≤ 0.05) but not with removal of the TCs. Proteobacteria , Bacteroidetes, and Fusobacteria were dominant in the microbial communities, but they showed little correlation with the TC removal. M. aquaticum can be employed as an effective means of TC removal from water. The co-existence of heavy metals should be considered when evaluating the removal potential of TCs in phytoremediation. Image 1 • M. aquaticum efficiently removed tetracycline antibiotics from hydroponic microcosms. • Cu(II) and tetracyclines were simultaneously removed when present as co-contaminants. • Lower Cu(II) concentrations (<1000 μg/L) promoted removal of the tetracyclines. • Plants were more important than biofilm microorganisms in removing the tetracyclines. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing β-catenin to potentiate the Wnt/β-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing β-catenin degradation to inactivate the Wnt/β-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing β-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation. • LGR6 expression is remarkably increased during osteogenic differentiation in MC3T3-E1. • LGR6 overexpression promotes the osteogenic differentiation of MC3T3-E1. • LGR6 overexpression activates the Wnt pathway by stabilizing β-catenin. • LGR6 knockdown inhibits osteogenic differentiation by suppressing the Wnt pathway. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications. • Rapamycin could ameliorate the phenotype of the immune-mediated AA model. • Rapamycin inhibits the proliferation of T cells by preventing cell cycle transition. • Rapamycin inhibits the mitochondrial metabolism of T cells in vivo. • Rapamycin exerts its function by inhibiting the mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a kind of small non-coding RNAs that have been reported to play a vital role in mediating host-pathogen interactions. High-throughput sequencing technology was applied to identify and illuminate mRNAs and miRNAs from grouper infected with Vibrio alginolyticus. The KEGG pathway enrichment analysis showed that the most significate DEGs are associated with Toll-like receptor signaling pathway and NOD-like receptor signaling pathway. We obtained 374 known miRNAs and 116 novel miRNAs. During them, there are 31 up-regulated miRNAs and 93 down-regulated miRNAs. miRNA-mRNA GO and KEGG analysis show that there are 90 miRNAs associated with the immune system. The target genes of immune-related miRNAs (miR-142, miR-146, miR-150, miR-155, miR-203, miR-205, miR-24, miR-31) and genes (CD80, IL-2, AMPK, PI3K) in Epinephelus coioddes were predicted and validated. This study provides an opportunity to further understanding the molecular mechanisms especially the immune system of miRNA regulation in Epinephelus coioddes host-pathogen interactions. • A comprehensive miRNA database was constructed for Epinephelus coioddes liver under Vibrio alginolyticus infection. • miR-142, miR-146, miR-150, miR-155, miR-203, miR-205, miR-24 and miR-31 were response to Vibrio alginolyticus infection • Key biological processes related to Epinephelus coioddes liver under Vibrio alginolyticus infection were identified. • The liver can also be an immune organ to protect groupers from viral infection. [ABSTRACT FROM AUTHOR]

Rice, the most consumed in Asian and constitute important source of amino acids. The present study evaluated the suitability of near-infrared reflectance spectroscopy to predict amino acid contents (AACs) using 1210 rice samples representing a wide range of grain qualities and genetic background. Calibration models established by combining different spectral derivatives, scatter and baseline correction methods, and regression algorithm were compared using full cross validation. A modified partial least square model (MPLS) with the spectral derivative treatment "2, 3, 3, 1" (2nd order derivative computed based on 3 data points, and 3 and 1 data points in the 1st and 2nd smoothing, respectively) and weighted multiplicative scattering correction (WMSC) method was identified as the best model for simultaneously measurement of 14 AACs in brown rice flour. The high model quality is reflected by RSQ of 0.914∼0.969, standard error of calibration (SEC) of 0.0187%∼0.0553%, 1-VR of 0.901∼0.955, SECV of 0.0214%∼0.0579%, and residual prediction deviation (RPD) of 2.58∼3.85. These results indicated that NIRS coupled with an appropriate pre-processing, multivariate regression could be a rapid and reliable method for quantification of AACs in rice breeding programs and quality control in the food industry. Factors that would influence model quality were investigated and discussed. • NIRS is capable of accurately quantifying 14 amino acids contents in diverse rice samples. • MPLS was the most robust regression method. • MSC and 2nd derivation were suitable pre-processing methods. • NIRS is applicable for high-throughput screening. [ABSTRACT FROM AUTHOR]

Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay utilizes the NanoLuc ® Binary Technology (NanoBiT) to monitor the covalent neddylation status of Cul1. A stable clonal cell line derived from HEK293 was developed that expressed a C-terminus LgBiT tagged-Cul1 and N-terminus SmBiT tagged-Nedd8. Using this cell line, we screened inhibitors that are known to disrupt Nedd8 biology and demonstrated that both inhibitors of Nedd8-activating enzyme (NAE) and Constitutive photomorphogenesis 9 signalosome (CSN) complex produce concentration and time dependent signal decreases and increases, respectively. The kinetics of both responses could be monitored in real time and demonstrated that modulation of the Nedd8 pathway occurs rapidly. Further characterization of the cellular components of this cell line was performed in order to quantify the various levels of Cul1, Nedd8 and NAE and determined to be near endogenous levels. There was no difference between control and stably transfected cell lines in viability studies of NAE and CSN inhibitors. Taken together, these results suggest that the NanoBiT assay can be used to monitor Cul1 neddylation specifically and in real time. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common neurodegenerative disease in aging individuals. Alternative splicing is reported to be relevant to AD development while their roles in etiology of AD remain largely elusive. We performed a comprehensive splicing transcriptome-wide association study (spTWAS) using intronic excision expression genetic prediction models of 12 brain tissues developed through three modelling strategies, to identify candidate susceptibility splicing introns for AD risk. A total of 111,326 (46,828 proxy) cases and 677,663 controls of European ancestry were studied. We identified 343 associations of 233 splicing introns (143 genes) with AD risk after Bonferroni correction (0.05/136,884 = 3.65 × 10−7). Fine-mapping analyses supported 155 likely causal associations corresponding to 83 splicing introns of 55 genes. Eighteen causal splicing introns of 15 novel genes (EIF2D , WDR33 , SAP130 , BYSL , EPHB6 , MRPL43 , VEGFB , PPP1R13B , TLN2 , CLUHP3 , LRRC37A4P , CRHR1 , LINC02210 , ZNF45-AS1 , and XPNPEP3) were identified for the first time to be related to AD susceptibility. Our study identified novel genes and splicing introns associated with AD risk, which can improve our understanding of the etiology of AD. • A comprehensive splicing transcriptome-wide association study was performed to identify candidate susceptibility splicing introns for AD risk. • Total 343 associations of 233 splicing introns (143 genes) with AD risk after Bonferroni correction (0.05/136,884 = 3.65 × 10-7) were identified. • Eighteen causal splicing introns of 15 novel genes were identified for the first time to be related to AD susceptibility. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are essential in initiating and driving allergic immune responses. However, there were inconsistent findings of the ILC2 levels in allergic rhinitis (AR) patients. This study investigated the ILC2 levels in the peripheral blood of house dust mite (HDM)-sensitized AR patients and their ability to secrete type 2 cytokines. The levels of ILC2s with phenotypic ILC2 characteristics were increased in the HDM-AR patients. The AR patients' symptom score and IL-13 levels were positively associated with the ILC2s in HDM-AR patients. The epithelial cytokine stimulation induced dramatic production of IL-5 and IL-13 in PBMCs of AR patients. We successfully sorted ILC2s from AR patients and identified their ability of type 2 cytokines production. The number of ILC2s increased in the HDM-AR patients and ILC2s produced the amount of T H 2 cytokines in the presence of epithelial cytokines, which suggested the important role of ILC2 in AR patients. [ABSTRACT FROM AUTHOR]