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Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics and anti-IBV functions of these ISGs as well as mechanisms underlying their differential induction are characterized. The results confirmed that these three ISGs were indeed differentially induced in H1299 and Vero cells infected with IBV, significantly more upregulation of IRF1, ISG15 and ISG20 was elicited in IBV-infected Vero cells than that in H1299 cells. Induction of these ISGs was also detected in cells infected with human coronavirus-OC43 (HCoV-OC43) and porcine epidemic diarrhea virus (PEDV), respectively. Manipulation of their expression by overexpression, knockdown and/or knockout demonstrated that IRF1 played an active role in suppressing IBV replication, mainly through the activation of the IFN pathway. However, a minor, if any, role in inhibiting IBV replication was played by ISG15 and ISG20. Furthermore, p53, but not IRF1, was implicated in regulating the IBV infection-induced upregulation of ISG15 and ISG20. This study provides new information on the mechanisms underlying the induction of these ISGs and their contributions to the host cell antiviral response during IBV infection. • IBV infection of H1299 and IFN-β-deficient Vero cells differentially regulates the expression of IRF1, ISG15 and ISG20. • Overexpression of IRF1 suppresses IBV replication mainly through the induction of IFN pathways. • The endogenous IRF1 plays a minor role in the inhibition of IBV replication and in the induction of ISG15 and ISG20. • Overexpression of ISG15 and ISG20 does not significantly suppress IBV replication. • IBV-induced ISG15 and ISG20 expression is partially p53-dependent, but not by IRF1. [ABSTRACT FROM AUTHOR]

Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism. • DNlg3 C-terminal fragment could translocate into the nuclear and regulate the transcription. • Dnlg3 null flies showed an increased expression of the innate immune response genes. • A single knockout of a synaptic molecule in Drosophila would lead to the stronger activation of the entire innate immune responses. [ABSTRACT FROM AUTHOR]

In this experiment, we investigated the effects of adding chlorogenic acid (CGA) to the diet on growth performance, immune function, inflammation response, antioxidant capacity and its related mechanisms of common carp (Cyprinus carpio). A total of 600 fish were selected and randomly divided into five treatment groups and fed with CGA containing 0 mg/kg (CK), 100 mg/kg (L100), 200 mg/kg (L200), 400 mg/kg (L400) and 800 mg/kg (L800) for 56 days. The results of the experiment were as follows: addition of CGA significantly increased the WGR, SGR, FER, and PER of common carp (P < 0.05). The addition of 400–800 mg/kg of CGA significantly increased the serum levels of LZM, AKP activity, C3 and C4 concentration, and increased immune function of common carp (P < 0.05). Regarding antioxidant enzyme activities, adding CGA significantly increased SOD, CAT, and GsH-Px activities, while decreasing MDA content (P < 0.05). Compared with the CK group, the mRNA expression levels of NF-κB , TNF-α , and IL-1β were decreased. The IL-10 and TGF-β were increased in the liver and intestines of the CGA supplemented group. Meanwhile, the addition of CGA also significantly up-regulated the mRNA expression levels of Nrf2 , HO-1 , SOD , CAT , and GPX (P < 0.05). CGA also positively contributed to the development of the carp intestinal tract, as demonstrated by decreased serum levels of DAO, D-LA, and ET-1. And the mucosal fold height was increased significantly with increasing levels of CGA. In conclusion, the addition of CGA in the feed can enhance the growth performance, immune function and antioxidant capacity of common carp, and improve the health of the intestine and liver. According to the results of this experiment, the optimal addition amount in common carp diets was 400 mg/kg. • Addition of 400 mg/kg chlorogenic acid can improve the growth performance of common carp. • Chlorogenic acid could improve the health of the liver and intestines of common carp. • Chlorogenic acid could enhance antioxidant capacity and immunity by modulating Nrf2 / NFκB signalling pathways. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing and life-threatening inflammatory disorder that mainly affect the intestinal tract. The mainstream therapies for moderate to severe IBD lie in the use of immunosuppressive agents. However, it encountered the problem of drug tolerance and significant adverse events. Therefore, identifying novel signal pathways involved in IBD is necessary to satisfy the unmet treatment needs of IBD patients. There existed some hints between iron and IBD, and was reported that ferroptosis induced in UC. However, as another important subtype of IBD, whether ferroptosis also occurred in CD remains unclear. In this study, we found that the dysregulation of iron, lipid peroxidation and redox homeostasis were involved in CD; the administration of ferroptosis inhibitor Ferrostatin-1 could alleviate pathological phenotypes of TNBS induced CD-like colitis in mice. Our results provide a new hopeful therapeutic strategy in treating CD, especially for those who suffered from the tolerance of existing immunosuppressive agent drugs. • Ferroptosis indicators were differentially expressed in biopsies from CD patients. • Ferroptosis occurred in TNBS induced colitis mice. • Ferroptosis inhibitor ferrostatin-1 ameliorated TNBS induced colitis in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • 12 new oligomeric phloroglucinols were isolated from tropic Rhodomyrtus tomentosa. • An enantiomeric mixture of 3a and 3b is an excellent h AChE inhibitor with an IC 50 value of 1.21 μM. • Molecular docking was used to uncover the possible mechanism of 3a and 3b with h AChE. • The racemic mixture of 3a and 3b showed the most anti-MRSA activity with MIC and MBC values of 0.50 μg/mL. • The SEM studies revealed that 3a and 3b could destroy the biofilm structures of MRSA. Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (h AChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a , 3b , 4b , and 5a), six new phloroglucinol trimers (6a , 6b , 7a , 7b , 8a , and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a / 3b shared a rare C-5 ′ formyl group, whereas 6a / 6b possessed a unique C-7 ′ aromatic ring. In addition, 7a / 7b and 8a / 8b were rare phloroglucinol trimers with a bis-furan and a C-6 ′ hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (h AChE) inhibitory activity with an IC 50 value of 1.21 ± 0.16 μM. The molecular docking studies of 3a and 3b in the h AChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 μg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents. [ABSTRACT FROM AUTHOR]

Spatial learning and memory are typically assessed to evaluate hippocampus-dependent cognitive and memory functions in vivo. Protein phosphorylation and dephosphorylation by kinases and phosphatases play critical roles in spatial learning and memory. Here we report that the Wip1 phosphatase is essential for spatial learning, with knockout mice lacking Wip1 phosphatase exhibiting dysfunctional spatial cognition. Aberrant phosphorylation of the Wip1 substrates p38, ATM, and p53 were observed in the hippocampi of Wip1 −/− mice, but only p38 inhibition reversed impairments in long-term potentiation in Wip1 -knockout mice. p38 inhibition consistently ameliorated the spatial learning dysfunction caused by Wip1 deficiency. Our results demonstrate that deletion of Wip1 phosphatase impairs hippocampus-dependent spatial learning and memory, with aberrant downstream p38 phosphorylation involved in this process and providing a potential therapeutic target. • Mice deficient in Wip1 (wild-type p53-induced phosphatase 1) exhibit spatial cognitive dysfunction. • Wip1 deficiency results in downstream aberrant phosphorylation of p38 MAPK in mouse hippocampi. • p38 inhibition reverses impaired learning and cognitive function in Wip1−/− mice. • The Wip1-p38 axis plays a vital role in spatial learning and memory. [ABSTRACT FROM AUTHOR]

Although accumulating evidence has revealed that autophagy inhibition contributes to the development of pathological cardiac hypertrophy, the mechanisms leading to declined autophagy activity in the hypertrophic heart remain to be elucidated. Exosomes are known to be important mediators of intercellular communication, and the involvement of exosomes in cardiovascular abnormities has attracted increasing attentions. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. Here, we investigated the potential role of CFs-derived exosomes in regulating cardiomyocyte hypertrophy and autophagy. Exosomes from rat CFs treated with angiotensin II (Ang II-CFs-exosomes) were collected and characterized. Our experiments showed that these exosomes could induce hypertrophic responses and impair autophagy activity in primary neonatal rat cardiomyocytes (NRCMs). Ang II-CFs-exosomes blocked the autophagic flux of NRCMs via inhibiting the formation of autolysosomes. Moreover, the pro-hypertrophic effects and autophagy inhibition induced by Ang II-CFs-exosomes was validated in mice receiving injection of the exosomes. These findings highlight a novel role of Ang II-CFs-exosomes in suppressing cardiomyocyte autophagy, which may help to better understand the pathogenesis of cardiac hypertrophy. • Ang II-CFs-exosomes induced hypertrophic responses and impaired autophagy activity in cardiomyocytes. • The autophagic flux in cardiomyocytes could be blocked by Ang II-CFs-exosomes. • Injection of Ang II-CFs-exosomes provoked cardiac hypertrophy and autophagy inhibition in mice. [ABSTRACT FROM AUTHOR]

Based on the anomalous Doppler effect, we put forward a proposal to enhance the conversion efficiency of the slow-wave electron cyclotron masers (ECM) under the resonance condition. Compared with previous studies, we add a second-order shaping term in the guild magnetic field. Theoretical analyses and numerical calculations show that it can enhance the conversion efficiency in the low-gain limit. The case of the initial velocity spread of electrons satisfying the Gaussian distribution is also analysed numerically. [ABSTRACT FROM AUTHOR]

For an arbitrary semisimple Frobenius manifold we construct Hodge integrable hierarchy of Hamiltonian partial differential equations. In the particular case of quantum cohomology the tau-function of a solution to the hierarchy generates the intersection numbers of the Gromov–Witten classes and their descendents along with the characteristic classes of Hodge bundles on the moduli spaces of stable maps. For the one-dimensional Frobenius manifold the Hodge hierarchy is an integrable deformation of the Korteweg–de Vries hierarchy depending on an infinite number of parameters. Conjecturally this hierarchy is a universal object in the class of scalar Hamiltonian integrable hierarchies possessing tau-functions. [ABSTRACT FROM AUTHOR]

We study the relationship between the behavior of global quantum correlations and quantum phase transitions in XY model. We find that the two kinds of phase transitions in the studied model can be characterized by the features of global quantum discord (GQD) and the corresponding quantum correlations. We demonstrate that the maximum of the sum of all the nearest neighbor bipartite GQDs is effective and accurate for signaling the Ising quantum phase transition, in contrast, the sudden change of GQD is very suitable for characterizing another phase transition in the XY model. This may shed lights on the study of properties of quantum correlations in different quantum phases. [ABSTRACT FROM AUTHOR]

We provide a family of general monogamy inequalities for global quantum discord (GQD), which can be considered as an extension of the usual discord monogamy inequality. It can be shown that those inequalities are satisfied under the similar condition for the holding of usual monogamy relation. We find that there is an intrinsic connection among them. Furthermore, we present a different type of monogamy inequality and prove that it holds under the condition that the bipartite GQDs do not increase when tracing out some subsystems. We also study the residual GQD based on the second type of monogamy inequality. As applications of those quantities, we investigate the GQDs and residual GQD in characterizing the quantum phase transition in the transverse field Ising model. [ABSTRACT FROM AUTHOR]

Highlights: [•] Beagles were exposed to BMEDA using intravenous administration to conduct a single dose 14-day acute toxicity study. [•] No lethality was observed in beagles during this 14-day acute toxicity study. [•] BMEDA was not associated with any adverse effects in beagles at doses of up to 2mg/kg. [Copyright &y& Elsevier]

Microplastics (MPs) have recently attracted much attention due to their widespread distribution in the aquatic environment. Microplastics can act as a vector of heavy metals in the aquatic environment, causing a potential threat to aquatic organisms and human health. This review mainly summarized the occurrence of microplastics in the aquatic environment and their interaction with heavy metals. Then, we considered the adsorption mechanisms of MPs and heavy metals, and further critically discussed the effects of microplastics properties and environmental factors (e.g., pH, DOM, and salinity) on the adsorption of heavy metals. Finally, the potential risks of combined exposure of MPs and heavy metals to aquatic biota were briefly evaluated. This work aims to provide a theoretical summary of the interaction between MPs and heavy metals, and is expected to serve as a reference for the accurate assessment of their potential risks in future studies. • Microplastics serve as vectors of heavy metals in the aquatic environment. • The possible mechanisms of heavy metal adsorption by microplastics are complex. • Microplastics properties and environmental factors affect heavy metal adsorption. • Co-exposure of microplastics and heavy metals may have different effects on aquatic biota. [ABSTRACT FROM AUTHOR]

[Display omitted] • Eight new and two naturally occurring acylphloroglucinol trimers were obtained from Callistemon salignus seeds. • An enantiomeric mixture of 2a/2b is an excellent h AChE inhibitors with an IC 50 value of 1.22 μM. • Molecular docking was used to uncover the possible mechanism of bioactive compounds. Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (h AChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A–H (1a , 1b , 2a , 2b , 3a , 3b , 4b , and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone–acylphloroglucinol–monoterpene adduct (6), were obtained and structurally characterized from the h AChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of h AChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b , 2a , and 2b are good h AChE inhibitors with IC 50 values of 1.22 ± 0.23, 2.28 ± 0.19, and 4.96 ± 0.39 μM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of h AChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we introduce the notion of infinite dimensional Jacobi structure to describe the geometrical structure of a class of nonlocal Hamiltonian systems which appear naturally when applying reciprocal transformations to Hamiltonian evolutionary PDEs. We prove that our class of infinite dimensional Jacobi structures is invariant under the action of reciprocal transformations that only change the spatial variable. The main technical tool is in a suitable generalization of the classical Schouten–Nijenhuis bracket to the space of the so called quasi-local multi-vectors, and a simple realization of this structure in the framework of supermanifolds. These constructions are used to compute the Lichnerowicz–Jacobi cohomologies and to prove a Darboux theorem for Jacobi structures with hydrodynamic leading terms. We also introduce the notion of bi-Jacobi structures, and consider the integrability of a system of evolutionary PDEs that possesses a bi-Jacobi structure. [Copyright &y& Elsevier]

Abstract: The Drinfeld–Sokolov construction associates a hierarchy of bihamiltonian integrable systems with every untwisted affine Lie algebra. We compute the complete sets of invariants of the related bihamiltonian structures with respect to the group of Miura-type transformations. [Copyright &y& Elsevier]

Abstract: Ancillary β-subunits regulate the voltage-dependence and the kinetics of Kv currents. The Kvβ proteins bind pyridine nucleotides with high affinity but the role of cofactor binding in regulating Kv currents remains unclear. We found that recombinant rat Kvβ1.3 binds NADPH (K d =1.8±0.02μM) and NADP+ (K d =5.5±0.9μM). Site-specific modifications at Tyr-307 and Arg-316 decreased NADPH binding; whereas, K d NADPH was unaffected by the R241L mutation. COS-7 cells transfected with Kv1.5 cDNA displayed non-inactivating currents. Co-transfection with Kvβ1.3 accelerated Kv activation and inactivation and induced a hyperpolarizing shift in voltage-dependence of activation. Kvβ-mediated inactivation of Kv currents was prevented by the Y307F and R316E mutations but not by the R241L substitution. Additionally, the R316E mutation weakened Kvα–β interaction. Inactivation of Kv currents by Kvβ:R316E was restored when excess NADPH was included in the patch pipette. These observations suggest that NADPH binding is essential for optimal interaction between Kvα and β subunits and for Kvβ-induced inactivation of Kv currents. [Copyright &y& Elsevier]

• Two new cycloneolignan enantiomers were isolated. • The absolute configurations were determined by ECD calculations. • Enantiomers exhibited neuroprotective activity. • Enantiomers exhibited activity by reducing the apoptosis ratio. A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5 µM compared with that of MPP+ treated group (62.00% at 1 mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) contributes to an increased risk of incident heart failure and sudden death, but there is still a lack of effective treatment in clinic. Recently, growing evidence has indicated that abnormal expression of microRNAs (miRNAs) plays a crucial role in cardiovascular diseases. In this research, the involvement of miRNA-214-3p in MI was explored. A mouse model of MI was established by ligation of the left anterior descending coronary artery, and primary cultures of neonatal rat cardiomyocytes (NRCMs) were submitted to hypoxic treatment to stimulate cellular injury in vitro. Our results showed that miR-214-3p level was significantly upregulated in the infarcted region of mouse hearts and in NRCMs exposed to hypoxia, accompanying with an obvious elevation of ferroptosis. Inhibition of miR-214-3p by antagomir injection improved cardiac function, decreased infarct size, and attenuated iron accumulation and oxidant stress in myocardial tissues. MiR-214-3p could also promote ferroptosis and cellular impairments in NRCMs, while miR-214-3p inhibitor effectively protected cells from hypoxia. Furthermore, dual luciferase reporter gene assay revealed that malic enzyme 2 (ME2) is a direct target of miR-214-3p. In cardiomyocytes, overexpression of ME2 ameliorated the detrimental effects and excessive ferroptosis induced by miR-214-3p mimic, whereas ME2 depletion compromised the protective role of miR-214-3p inhibitor against hypoxic injury and ferroptosis. These findings suggest that miR-214-3p contributes to enhanced ferroptosis during MI at least partially via suppressing ME2. Inhibition of miR-214-3p may be a new approach for tackling MI. • MiR-214-3p is upregulated in MI mice hearts and hypoxic cardiomyocytes. • Inhibition of miR-214-3p protects mice against MI injury and attenuates ferroptosis. • ME2 is identified as a downstream effector miR-214-3p. • MiR-214-3p induces ferroptosis by suppressing ME2, thereby contributing to MI. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO 2 ) has gained increasing interest in materials research due to its outstanding properties and promising applications in a wide range of fields. From this perspective, we report the synthesis of custom-designed anatase TiO 2 submicrometer particles coated with partial Au shells (ATiO 2 -AuShl). The synthetic strategy used herein yields uniformly shaped monodisperse particles. Amorphous TiO 2 core particles were synthesized using template-free oxidation and hydrolysis of titanium nitride (TiN); subsequent hydrothermal treatment generated anatase TiO 2 (ATiO 2 ) particles. Coating ATiO 2 particles with partial Au shells was accomplished using a simple seeded-growth method. Evaluation of the optical properties of these ATiO 2 -AuShl particles showed that these submicrometer composites exhibited an intense absorption peak for TiO 2 in the UV region (∼326 nm) and a broad extinction band in the visible range (∼650 nm) arising from the incomplete Au shell. These ATiO 2 -AuShl composite particles provide a unique and effective means for broadening the optical response of TiO 2 -based nano- and micron-scale materials. The simplicity of our synthetic method should broaden the application of ATiO 2 -AuShl particles in various visible light-driven technologies. [ABSTRACT FROM AUTHOR]

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT 1 R) could be involved in depression. Herein we hypothesize that CysLT 1 R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT 1 R in the astrocytes that participate in occurrence of depression. We found that CysLT 1 R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT 1 R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT 1 R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT 1 R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT 1 R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT 1 R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by β-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT 1 R of DG. Our study demonstrated that astrocyte CysLT 1 R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT 1 R could be a potential target for developing novel drugs of anti-depression. • CysLT 1 R was significantly increased in the astrocyte of DG in depression-like mice. • Overexpression of CysLT 1 R in the astrocyte of DG induced depression-like behaviors. • CysLT 1 R AcKO or knockdown in the astrocyte of DG improved depression-like behaviors. • CysLT 1 R downregulation antidepression is related to synaptic plasticity enhancement. [ABSTRACT FROM AUTHOR]

Ammonia-oxidation process directly contribute to soil nitrous oxide (N 2 O) emissions in agricultural soils. However, taxonomy of the key nitrifiers (within ammonia oxidising bacteria (AOB), archaea (AOA) and complete ammonia oxidisers (comammox Nitrospira)) responsible for substantial N 2 O emissions in agricultural soils is unknown, as is their regulation by soil biotic and abiotic factors. In this study, cumulative N 2 O emissions, nitrification rates, abundance and community structure of nitrifiers were investigated in 16 agricultural soils from major crop production regions of China using microcosm experiments with amended nitrogen (N) supplemented or not with a nitrification inhibitor (nitrapyrin). Key nitrifier groups involved in N 2 O emissions were identified by comparative analyses of the different treatments, combining sequencing and random forest analyses. Soil cumulative N 2 O emissions significantly increased with soil pH in all agricultural soils. However, they decreased with soil organic carbon (SOC) in alkaline soils. Nitrapyrin significantly inhibited soil cumulative N 2 O emissions and AOB growth, with a significant inhibition of the AOB Nitrosospira cluster 3a.2 (D11) abundance. One Nitrosospira multiformis -like OTU phylotype (OTU34), which was classified within the AOB Nitrosospira cluster 3a.2 (D11), had the greatest importance on cumulative N 2 O emissions and its growth significantly depended on soil pH and SOC contents, with higher growth at high pH and low SOC conditions. Collectively, our results demonstrate that alkaline soils with low SOC contents have high N 2 O emissions, which were mainly driven by AOB Nitrosospira cluster 3a.2 (D11). Nitrapyrin can efficiently reduce nitrification-related N 2 O emissions by inhibiting the activity of AOB Nitrosospira cluster 3a.2 (D11). This study advances our understanding of key nitrifiers responsible for high N 2 O emissions in agricultural soils and their controlling factors, and provides vital knowledge for N 2 O emission mitigation in agricultural ecosystems. • Soil N 2 O emissions increase with soil pH increase in fertilised cropland soils. • High N 2 O emissions in alkaline soils are derived from AOB-dominated nitrification. • Nitrification-related N 2 O emissions are negatively correlated with SOC content. • Nitrosospira cluster 3a.2 is the main AOB taxa responsible for high N 2 O emissions. • OTU34 could be a candidate biomarker for predicting nitrification-related N 2 O emissions. [ABSTRACT FROM AUTHOR]

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid β-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism. [Display omitted] [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0–6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0–6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals. [Display omitted] • N-acetylcysteine (NAC) could improve the morphology and health of hepatopancreas in common carp. • The anti-inflammatory and antioxidant effects of NAC via the MAPK/NF-κB/Nrf2 signalling pathway. • We recommend adding 3.0 g/kg NAC to the diets of juvenile common carp. [ABSTRACT FROM AUTHOR]

Maize is an important food crop in the world, but the yield and quality of maize have been significantly reduced due to the impact of insect pests. In order to address this issue, the cry1Ah gene was subjected to error-prone PCR for mutagenesis, and subsequently, the mutant cry1Ah-1 gene was introduced into maize inbred line GSH9901 callus using the Agrobacterium -mediated method. The T2 generation transformed plants were obtained by subculture, and 9 transgenic positive plants were obtained by molecular detection which was carried out by PCR, qRT-PCR, Bt gold-labeled immunoassay test strips, Western blot and ELISA. It was found that the Cry1Ah-1 gene could be transcribed normally in maize leaves, of which OE1 and OE3 had higher relative expression levels and could successfully express proteins of 71.94 KD size. They were expressed in different tissues at the 6-leaf stage, heading stage and grain-filling stage, and could ensure the protection of maize from corn borer throughout the growth period. The biological activities of OE1 and OE3 were tested indoors and in the field, and the results showed that in indoors, the corn borer that fed on OE1 and OE3 corn leaves had a mortality rate of 100 % after 3 days; in the field, OE1 and OE3 had strong insecticidal activity against corn borer , reaching a high resistance level. In conclusion, the transgenic cry1Ah-1 maize has a strong insecticidal effect on corn borer , and has a good prospect of commercialization. • cry1Ah-1 mutant gene was introduced into maize callus by Agrobacterium-mediated method. • This gene is expressed in different tissues at different times, which can ensure the protection of maize from corn borer. [ABSTRACT FROM AUTHOR]

Genomic data can improve our understanding on the phylogenetic relationship among Tibetan highland fishes. The whole mitochondrial genome of Gymnocypris eckloni generated in this study is 16,784 bp in length, containing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes, and one non-coding control region (D-Loop). Phylogenetic analysis recovers a non-monophyetic population of G. eckloni in the Qaidam basin, representing two distinct lineages designated 'Qiadam A' and 'Qaidam B', within Qaidam A clustering with Chuanchia labiosa and Schizopygopisis pylzovi captured in the Yellow River and Qaidam B grouping with G. eckloni from the Yellow River. Our research may helpful to further reconsideration of clearer taxonomy and improvement of biodiversity conservation strategy of Tibetan highland fishes. • First report of mitogenome of Gymnocypris eckloni captured in type locality. • Phylogenetic analysis recovers a non-monophyetic population of G. eckloni in the Qaidam basin. • Convergent evolution may occur between an unknown species and G. eckloni in Qaidam basin. [ABSTRACT FROM AUTHOR]

Starch from several plant sources, namely Japonica rice starch (JRS), waxy rice starch (WRS), corn starch (CS), wheat starch (WS), pea starch (PeS), potato starch (PtS), and tapioca starch (TS), were separately pasted into amorphous mixtures with whey protein isolate (WPI). The physicochemical and emulsifying properties of the seven amorphous starch–WPI mixtures were characterized. Each starch–WPI mixture showed a lower fluorescence intensity than that of WPI alone. The mixtures containing PtS, PeS, CS, and WS, which have higher amylose content, had lower fluorescence intensities than the other mixtures. The PeS-, CS-, and WS-WPI mixtures had lower zeta-potentials and larger particle sizes, contained remnants of starch granules, and exhibited a low paste viscosity. The droplet sizes of emulsions stabilized with the amorphous starch–WPI mixtures ranged from 2.82 to 7.04 μm. The emulsions stabilized with either PtS-, PeS-, CS-, or WS-WPI mixtures had smaller droplet sizes and higher storage modulus (G′) values and showed no creaming after storage for 30 d, whereas severe creaming occurred in the emulsions containing WRS-, TS-, or JRS-WPI mixtures. Microscopic imaging revealed that the mixtures-stabilized emulsions were composed of WPI-adsorbed spherical droplets with starch in the continuous phase. • Amorphous starch–WPI mixtures were prepared with seven types of starches. • Starches with high amylose content were more likely to form complexes with WPI. • Mixtures with high amylose content showed better emulsifying ability. • Emulsions with starch granule remnants showed better centrifugal stability. • The oil–water interfaces are mainly composed of WPI-related components. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder impairing memory and cognition. In this study, we describe the immunogenicity and protective efficacy of the novel recombinant 6Aβ15-TF chimeric antigen as a subunit protein vaccine for AD. Recombinant 6Aβ15-TF chimeric vaccine induced strong Aβ-specific humoral immune responses without Aβ-specific T cell immunity in C57/BL6 and 3 × Tg-AD mice at different ages. As an early immunotherapy model for AD, this vaccine induced high titers of long-lasting anti-Aβ42 antibodies in aged 3 × Tg-AD mice, which led to improve behavioral performance and markedly reduced the levels of insoluble and soluble Aβ and Aβ oligomers. In agreement with these findings, immunotherapy with 6Aβ15-TF prevented the Aβ-induced decrease of presynaptic and postsynaptic proteins in aged 3 × Tg-AD mice. Our results suggest that this novel and highly immunogenic recombinant 6Aβ15-TF chimeric vaccine provides neuroprotection in AD mice and can be considered an effective AD candidate vaccine. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new method for energy storage ejection is proposed using superelastic SMA wire. • A novel concept of correlating energy and SMA resistance change rate is proposed. • Ejection energy density and energy conversion efficiency are investigated by test. • Theoretical prediction model for ejection energy density of SMA wire is developed. Superelastic shape memory alloy (SMA) wire is a memorable deformation material with large resilience and high energy density. In this paper, a revolutionary and yet explainable property of the SMA is investigated and confirmed: superelastic SMA energy storage and release can be quantitatively measured using electrical resistance. This finding boosted the SMA with significant advantages and potential in the field of mechanical energy storage and ejection release. A state-of-the-art energy storage ejection device is designed to test the relationship among SMA wires' stress, strain, and electrical resistance. The resistance change rate, ejection energy density and energy conversion efficiency are studied in the SMA wire energy tests. The experimental results confirm that the resistance change rate of the superelastic SMA wire has a stable linear relationship with the strain. The ejection energy density increases with the resistance change rate. A theoretical model of the relationship between the ejection energy density and resistance change rate is established based on the experimental results. In conclusion, the superelastic SMA wire can achieve sophisticated tasks that require 'programmable' and predictable energy storage or ejection. [ABSTRACT FROM AUTHOR]

A novel biochar/MgAl-layered double hydroxides composite (CB-LDH) was prepared for the removal of crystal violet from aqueous solution by pyrolyzing MgAl-LDH pre-coated ramie stem ( Boehmeria nivea (L.) Gaud.). Pyrolysis played dual role for both converting biomass into biochar and calcining MgAl-LDH during the pyrolysis process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and zeta potential analysis were used to characterize the CB-LDH. The results of characterization suggested that the calcined LDH was successfully synthesized and coated on biochar. The resulted CB-LDH had higher total pore volume and more functional groups than the pristine biochar. Adsorption experimental data fitted well with the pseudo-second order kinetics model and the Freundlich isotherm model. The rate-controlled step was controlled by film-diffusion initially and then followed by intra-particle diffusion. Thermodynamic analysis showed that the adsorption of crystal violet was a spontaneous and endothermic process. The higher pH and temperature of the solution enhanced the adsorption performance. CB-LDH could also have excellent ability for the removal of crystal violet from the actual industrial wastewater and groundwater with high ionic strength. LDH adsorption, electrostatic attraction, pore-filling, π–π interaction and hydrogen bond might be the main mechanisms for crystal violet adsorption on CB-LDH. The results of this study indicated that CB-LDH is a sustainable and green adsorbent with high performance for crystal violet contaminated wastewater treatment and groundwater remediation. [ABSTRACT FROM AUTHOR]

Due to the mass production and daily use of plastic products, the potential toxicity of microplastics to the water environment has attracted worldwide attention. In this work, the effect of typical microplastics (PET) on the performance of activated sludge from membrane bioreactors (MBR) was evaluated. The impacts on biological removal efficiency were unconspicuous with continuous dosing of 60 particles/L. However, further investigations revealed that PET particle accumulation caused adverse impacts on settleability and dewaterability. The SVI value increased from 53.3 ml/g MLSS to 69.9 ml/g MLSS and the CST in the PET reactor increased by 22%. Nevertheless, hydrophobicity was reduced by 49.2%. Mechanism studies exposed that the PET microplastics accumulation improved extracellular polymeric substances (EPS) from 116.96 mg/L to 138.70 mg/L and caused cell membrane damage. The abundance and diversity of microbial community reduced in activated sludge in PET reactor compared with control reactor. These phenomena revealed a possible hypothesis that the microplastic particles increased EPS and cytotoxicity of activated sludge. However, the rate of transmembrane pressure (TMP) build-up was significantly mitigated in PET-MBR compared to that in a control-MBR (1.27 folds), which attributes that physical scour of particles may still alleviate membrane contamination in MBR. • Membrane biofouling was alleviated due to physical scouring of PET particles. • The physicochemical properties of sludge were changed after long-term PET exposure. • Accumulation of PET particles caused EPS secretion and cell membrane damage. • Long-term exposure to PET changed the microbial community of MBR system. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. Here we investigate the effects of two novel liver x receptor (LXR) ligands (T0901317 or GW3965) on the development of acquired resistance to an EGFR TKI gefitinib. We observed known mechanisms of acquired resistance to EGFR TKI, including the EGFR T790M mutation, MET gene amplification and loss of PTEN in the gefitinib-resistant HCC827-8-1 cells. However, we found expression of MET was lower in HCC827-8-1 cells than in HCC827 cells. T0901317 or GW3965 inhibited Akt activation and sensitized HCC827-8-1 cells to gefitinib-induced cytotoxicity. In contrast, LXR ligands alone had no significant effect on HCC827-8-1 cells. In conclusion, this combined treatment may be of interest for treatment of lung adenocarcinomas harboring EGFR mutations and acquired resistance to gefitinib. [ABSTRACT FROM AUTHOR]

The risk of cardiovascular complications in diabetic patients is mainly associated with endothelial dysfunction. Reduced number of EPCs and impaired function of EPCs in diabetes result in imbalance of endothelial homeostasis and dysfunction of vessels. In patients with diabetes mellitus, plasma levels of asymmetric dimethylarginine (ADMA) were elevated, while the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) were reduced. In the present study, we investigated the role of the DDAH2/ADMA pathway in the senescence of EPCs in type 2 diabetic patients and cultured EPCs treated with high glucose. The results showed that the percentage of senescent EPCs increased while the expression of DDAH2 decreased concomitantly with an increase in the plasma levels of ADMA in patients with type 2 diabetes mellitus (T2DM). Similar results were seen in cultured EPCs treated with high glucose. Exogenous application of ADMA accelerated the senescence of EPCs in a dose-dependent manner, and overexpression of DDAH2 inhibited high glucose-induced EPCs senescence. In addition, it has also been reported that DDAH/ADMA pathway is regulated by silent information regulator 1 (SIRT1) in endothelial cell. In the present study, we found decreased expression of SIRT1 both in T2DM patients and EPCs pretreated with high glucose. And resveratrol (activating SIRT1) inhibited high glucose-induced EPCs senescence by upregulating the expression of DDAH2 and decreasing the levels of ADMA. Taken together, we concluded that DDAH2/ADMA is involved in the accelerated senescence of EPCs in diabetes, which is associated with the activation of SIRT1. [ABSTRACT FROM AUTHOR]

Cream is usually used during baking and contributes a pleasant aroma to the baked foods, but the effect of its polar components on the cream flavor is not fully understood. In this study, the polar components were extracted by using ethanol, and then were analyzed by 1H nuclear magnetic resonance (NMR). The main compositions in the extraction were lactose, phospholipids, free amino acids and free fatty acids. Then all the samples were baked at 160 °C for 30 min , respectively. GC-MS analysis showed that the polar components could generate lots of odorants, and with the addition of polar components, the lipid-derived volatile compounds in cream were significantly increased and varied, as well as Maillard reaction and caramelization products, especially butanoic acid, hexanal, (E,E)-2,4-decadienal, furfural, furaneol, maltol, methylpyrazine, 2,3-dimethylpyrazine, 2-methyl and 3-methylbutanal. On the contrary, the ethanol-treated cream sample had less odorants. Sensory analysis confirmed that the caramel and roasted notes were significantly enhanced with the addition of polar components, the ethanol-treated cream and polar components sample was similar to the cream in the attributes of milk, sweet and buttery. These data indicated that polar components in cream could be used as a functional flavor enhancer. [Display omitted] • Volatiles in heated cream were extracted and analyzed by HS-SPME-GC-MS. • Polar components extracted by ethanol were analyzed by NMR. • Polar components promote lipid oxidation, Maillard reaction and caramelization. • Polar components enhanced the 'caramel' and 'roasted' flavor of heated cream. • Polar components could be of potential use to improve the baking flavor of foods. [ABSTRACT FROM AUTHOR]

Abstract: Active amyloid-beta (Aβ) immunotherapy is under investigation to prevent or treat Alzheimer disease (AD). We describe here the immunological characterization and protective effect of DNA epitope chimeric vaccines using 6 copies of Aβ1-15 fused with PADRE or toxin-derived carriers. These naked 6Aβ15-T-Hc chimeric DNA vaccines were demonstrated to induce robust anti-Aβ antibodies that could recognize Aβ oligomers and inhibit Aβ oligomer-mediated neurotoxicity, result in the reduction of cerebral Aβ load and Aβ oligomers, and improve cognitive function in AD mice, but did not stimulate Aβ-specific T cell responses. Notably, toxin-derived carriers as molecular adjuvants were able to substantially promote immune responses, overcome Aβ-associated hypo-responsiveness, and elicit long-term Aβ-specific antibody response in 6Aβ15-T-Hc-immunized AD mice. These findings suggest that our 6Aβ15-T-Hc DNA chimeric vaccines can be used as a safe and effective strategy for AD immunotherapy, and toxin-derived carrier proteins are effective molecular adjuvants of DNA epitope vaccines for Alzheimer's disease. [Copyright &y& Elsevier]

Ferredoxin reductase (FDXR), a mitochondrial membrane-associated flavoprotein, is essential for electron transfer and modulates p53-dependent apoptosis in cancer cells.FDXR may be implicated in epidermal and sebocytic differentiation, but its explicit function in sebocytes remains to be elucidated. In the present study, immunohistochemistry revealed that FDXR expression was increased in sebaceous cells of acne lesions. FDXR, PPARγ, LXRα/β, SREBP1 and Sox9 expression was incremental during sebocyte differentiation. FDXR overexpression induced by Ad-GFP-FDXR infection enhanced differentiation, reactive oxygen species (ROS), lipogenesis and PPARγ expression, and consequnently inhibited proliferation in SZ95 sebocytes. Flow cytometry showed that FDXR overexpression induced significant blockade of G2/M phase but had no effect on sub-G1 (apoptotic) sebocytes. Insulin-like growth factor-1 (IGF-1)-induced FDXR and PPARγ expression and lipogenesis were abolished by pretreatment with PI3K inhibitor LY294002. These results suggest that FDXR overexpression might promote differentiation and lipogenesis via ROS production and suppress proliferation via G2/S blockade in SZ95 sebocytes. IGF-1 could facilitate differentiation and lipogenesis through PI3K/Akt/FDXR pathway. FDXR could serve as a potential marker of advanced sebaceous differentiation, and its overexpression may be involved in the development of acne lesions. • FDXR expression is increased in sebaceous cells of acne lesions. • FDXR may enhance sebocyte differentiation and lipogenesis via ROS production. • FDXR might inhibit proliferation through inducing G2/S blockade. • IGF-1 could facilitate sebaceous differentiation and lipogenesis via PI3K/Akt/FDXR pathway. [ABSTRACT FROM AUTHOR]

Abstract: Yeast artificial chromosomes (YACs) as transgenes in transgenic animals are likely to ensure optimal expression levels. Microinjection of YACs is the exclusive technique used to produce YACs transgenic livestock so far. However, low efficiency and high cost are its critical restrictive factors. In this study, we presented a novel procedure to produce YACs transgenic livestock as mammary gland bioreactor. A targeting vector, containing the gene of interest—a human serum albumin minigene (intron 1, 2), yeast selectable marker (G418R), and mammalian cell resistance marker (neor), replaced the α-lactalbumin gene in a 210kb human α-lactalbumin YAC by homogeneous recombination in yeasts. The chimeric YAC was introduced into goat fetal fibroblasts using polyethylene glycol-mediated spheroplast fusion. PCR and Southern analysis showed that intact YAC was integrated in the genome of resistant cells. Perhaps, it may offer a cell-based route by nuclear transfer to produce YACs transgenic livestock. [Copyright &y& Elsevier]

• Four pairs of new enantiomeric alkaloids were isolated. • The absolute configurations were determined by ECD calculations. • Enantiomers exhibited neuroprotective activity. • Enantiomers exhibited activity by reducing the apoptosis ratio. In the current study, four pairs of new enantiomeric alkaloids (1a / 1b - 4a / 4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H 2 O 2 -induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively. [ABSTRACT FROM AUTHOR]