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Nicotinic acetylcholine receptor (nAChR) is recognized as a significant insecticide target for neonicotinoids and some agonists. In this study, the nAChR α1 subunit from Apis mellifera was first found to be narrowly tuned to different bee toxicity insecticides, namely, sulfoxaflor (SFX) and flupyradifurone (FPF). Hence, novel sulfoximine derivatives 7a-h were rationally designed and synthesized by introducing a benzo[ d ][1,3]dioxole moiety into a unique sulfoximine skeleton based on the binding cavity characteristics of Amelα1/ratβ2. The two electrode voltage clamp responses of 7a-h were obviously lower than that of SFX, indicating their potentially low bee toxicity. Besides, representative compounds 7b and 7g exhibited low bee toxicity (LD 50 > 11.0 μg/bee at 48 h) revealed by acute contact toxicity bioassays. Molecular modelling results indicated that Ile152, Ala151, and Val160 from honeybee subunit Amelα1 and Lys144 and Trp80 from aphid subunit Mpα1 may be crucial for bee toxicity and aphicidal activity, respectively. These results clarify the toxic mechanism of agonist insecticides on nontargeted pollinators and reveal novel scaffold sulfoximine aphicidal candidates with low bee toxicity. These results will provide a new perspective on the rational design and highly effective development of novel eco-friendly insecticides based on the structure of the nAChR subunit. [Display omitted] • nAChR α1 subunit from Apis mellifera was related to bee toxicity of sulfoxaflor. • Novel low bee-toxicity sulfoximine aphicides were discovered by targeting Amelα1/ratβ2 complex. • Some residues were critical for aphicidal activity and bee toxicity, respectively. [ABSTRACT FROM AUTHOR]

The resistance and ecotoxicity of fungicides seriously restrict our ability to effectively control Magnaporthe oryzae. Discovering fungicidal agents based on novel targets, including Mo TPS1, could efficiently address this situation. Here, we identified a hit VS-10 containing an isopropanolamine fragment as a novel Mo TPS1 inhibitor through virtual screening, and forty-four analogs were synthesized by optimizing the structure of VS-10. Utilizing our newly established ion-pair chromatography (IPC) and leaf inoculation methods, we found that compared to VS-10, its analog j11 exhibited substantially greater inhibitory activity against both Mo TPS1 and the pathogenicity of M. oryzae. Molecular simulations clarified that the electrostatic interactions between the bridging moiety of isopropanolamine and residue Glu396 of contributed significantly to the binding of j11 and Mo TPS1. We preliminarily revealed the unique fungicidal mechanism of j11 , which mainly impeded the infection of M. oryzae by decreasing sporulation, killing a small portion of conidia and interfering with the accumulation of turgor pressure in appressoria. Thus, in this study, a novel fungicide candidate with a unique mechanism targeting Mo TPS1 was screened and discovered. [Display omitted] • An isopropanolamine inhibitor against Mo TPS1, VS-10, was discovered by virtual screening. • The optimized isopropanolamine compound j11 substantially inhibited Mo TPS1 and the pathogenicity of M. oryzae. • The electrostatic interaction of isopropanolamine compound j11 and Glu396 in Mo TPS1 was vital for their binding. • Isopropanolamine compound j11 had unique fungicidal mechanisms differing from those of commercial fungicides. [ABSTRACT FROM AUTHOR]

• The relationship was explored between the oil-water partition coefficient (logP) and the bee-toxicity for commercial nicotinic acetylcholine receptor (nAChR) competitive modulators in this work. • Two series of novel butenolide derivatives (I-01∼I-14, II-01∼II-13) containing different hydrophobic group were designed, synthesized and discovered that target compounds showed moderate insecticidal activity against A. glycines. • Compounds I-01, II-05 and II-11 were with higher insecticidal activity against Aphis glycines , lower contact bee-toxicity and lower calculated logP values among all synthesized compounds. • Molecular dynamics simulations indicated that three butenolide compounds had some hydrogen bonding or π-π stacking interactions with insect acetylcholine binding protein (AChBP). The possible bee-toxicity mechanism of action for novel butenolide compounds were explored based on nAChR function subunit AmeIα8/ratβ2. The discovery of new neonicotinoid alternatives with high efficiency against pests and eco-safety toward bees has become an increasingly urgent need in recent years. The relationship between the oil-water partition coefficient (logP) and the bee-toxicity of commercial nicotinic acetylcholine receptor (nAChR) competitive modulators was explored in this work. Compared compounds with a high bee-toxicity, compounds with low bee-toxicity were found to have higher logP values. Therefore, two series of novel butenolide derivatives with different hydrophobic groups were designed and synthesized by including different hydrophobic groups. The insecticidal activity study showed that compounds I-01 (LC 50 =112.96 μg/mL), II-05 (LC 50 =124.68 μg/mL), and II-11 (LC 50 =87.89 μg/mL) were with higher insecticidal activity against Aphis glycines and lower calculated logP values among all synthesized compounds. Molecular dynamics simulations indicated that three butenolide compounds formed some hydrogen bonding or π-π stacking interactions with insect acetylcholine binding protein (AChBP). In addition, the bee-toxicity bioassay also showed that compounds I-01, II-05 and II-11 were with much lower contact bee-toxicity than imidacloprid. The possible mechanism of the bee toxicity of the novel butenolide compounds was explored based on the nAChR function subunit AmeIα8/ratβ2. This study will provide rational guidance on novel butenolide compounds as low-bee-toxicity candidates based on their molecular hydrophobic properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Parenting styles are associated with children's psychological resilience. However, the underlying mechanisms of this have not been investigated. Parenting styles influence how individuals respond to self-inflicted errors, and error monitoring is related to psychological resilience. Therefore, this study proposed that error monitoring might be a bridging factor between parenting styles and psychological resilience. Seventy-two young healthy adults were recruited for this study. Parenting styles were assessed using the Parental Bonding Instrument, and psychological resilience was measured using the Connor–Davidson Resilience Scale. Error monitoring was investigated in the Flanker task using event-related potentials (ERPs), and two error-related components of ERPs were measured: error-related negativity (ERN) and error positivity. Mediation analyses showed that the ERN partially mediated the relationship between parenting styles and psychological resilience. Specifically, a higher level of self-reported parental overprotection was related to larger ERN amplitude, which in turn was associated with lower psychological resilience. Additionally, a higher level of self-reported parental allowance of autonomy was related to lower ERN amplitude, which in turn was linked to higher psychological resilience. These results suggest that shaping children's sensitivity in early automatic error detection is one possible mechanism through which parental styles influence their psychological resilience. • We examined the relationship among parenting, error monitoring and resilience. • Sensitivity to errors mediates the relationship between parenting and resilience. • More negative parenting links with lower resilience through larger ERN amplitude. • More positive parenting links with higher resilience through smaller ERN amplitude. [ABSTRACT FROM AUTHOR]

• The hydrogen bond interactions are crucial to small molecules binding to ApisOBP3. • Rational design strategy was used based on the binding cavity feature of ApisOBP3. • A novel acylpiperidine scaffold was firstly found to be aphid-repellent activity. Odorant-binding protein (OBP) is a promising potential target and can be used as a template for developing insect control agents due to its ability to bind to and transport semiochemicals to olfactory receptors, thus triggering behavioural responses among insects. In this study, 27 novel acylpiperidine analogues were designed and synthesised by introducing the hydrophobic long chain of the aphid alarm pheromone (E)-β-farnesene (EβF) into the polar acylpiperidine group of the commercial insect repellent icaridine based on the binding cavity characteristics of an OBP of the pea aphid Acyrthosiphon pisum , ApisOBP3. Compound 14c displayed good repellent activity against the pea aphids with a repellence rate of 61.5% at a concentration of 6 μg/μL. The equilibrium dissociation constant (K i) of compound 14c against ApisOBP3 was 20.92 μM in competitive fluorescence binding assays; this value is similar to the K i of the commercial insect repellent icaridine (20.56 μM). Molecular dynamics simulation revealed that the EβF long chain of compound 14c showed considerable hydrophobic interactions with the binding domain of ApisOBP3. Moreover, the acylpiperidine moiety of compound 14c formed one hydrogen bond and multiple carbon–hydrogen bonds with the Phe2 and Asn109 residues, respectively. The binding free energy analysis indicated that the contribution of the van der Waals force to the binding affinity was approximately twice as great as that of the electrostatic force. These studies provide significant guidance for the rational designing and efficient identification of novel insect repellent agents. [ABSTRACT FROM AUTHOR]

• This cross-sectional study was conducted during the initial outbreak of the COVID-19 epidemic. • Higher level of perceived stress due to the COVID-19 epidemic was related with more emotional distress. • Stress related increase in emotional distress is mediated by boredom proneness. • Positive coping strategies act as a buffer in alleviating emotional distress under stress. The outbreak of a novel coronavirus (COVID-19) pandemic was a great threat to the physical and mental health of the general population. Our research aimed to investigate the relationship between perceived stress and emotional distress during the initial outbreak. Furthermore, potential risks and protective factors, i.e., coping and boredom proneness, of stress-related emotional distress were also explored. Data from 3233 participants in China were collected through an online survey platform during the initial outbreak of the COVID-19 from January 31 to February 9 in 2020. Results showed that higher perceived stress was associated with more emotional distress including depression, fear, compulsion-anxiety, neurasthenia, and hypochondria. Boredom proneness significantly and positively mediated the relationship between perceived stress and emotional distress. Moreover, coping style moderated the stress-emotional distress relationship, i.e., individuals who mainly adopted positive coping strategies suffered fewer symptoms of depression, compulsion-anxiety, and neurasthenia under stress, while negative coping strategies aggravated emotional distress. These results from the present study provide practical value for mental health intervention during the emergent public health events. [ABSTRACT FROM AUTHOR]

The nicotinic acetylcholine receptor (nAChR), as an attractive target acted by neonicotinoid insecticides, was paid more and more attention in recent years. The mode of action study on neonicotinoids toward nAChR would present significant guidance on rational molecular design to further discover new insecticides. Four neonicotinoids including commercial agents imidacloprid and flupyradifurone, two previously synthesized compounds guadipyr and ethoxythiagua in our lab were docked into a putative model of aphid and honeybee nAChR, respectively, to explore the binding and selective mechanism of neonicotinoids in this study. The obtained results showed that a traditional H-bond interaction, as a dominating electrostatic driving force, always conferred the binding of four neonicotinoids not only to target aphid receptor but also to non-target honeybee one. Four neonicotinoids almost showed uniformly binding conformation into aphid receptor, namely, a vital electronegative nitro or butenolide group to be conserved to nestle in a non-selective β subunit. The bioassay study on Aphis gossypii also confirmed to be their excellent insecticidal activity with a lower LC 50 value of 0.028–3.2 μg/mL. However, to non-target honeybee receptor, this special nitro or butenolide group of four neonicotinoids was no longer only binding to the non-selective β subunit of receptor. Three among four neonicotinoids like flupyradifurone, guadipyr and ethoxythiagua as a case of low bee-toxicity reported in the previous study, were happened to display an exactly inverted binding orientation, namely, an unusual electronegative group captured another selective α subunit. However, this high bee-toxicity imidacloprid remained one conserved conformation into the non-selective β subunit as that seen from aphid receptor. This unique molecular mechanism of selectively binding to honeybee receptor, particularly to different subunit, was proposed cautiously to be one of factor determined the distinctive bee-toxicity for four neonicotinoids. These findings on the diverse mode of action for neonicotinoids to target and non-target receptor would be helpful for on novel insecticides design with high bioactivity as well as good selectivity based on the structure of different insect nAChR. Image 1 • H-bond conferred the binding of neonicotinoids to target and non-target receptor. • Neonicotinoids showed uniformly bound conformation buried to aphid receptor. • Different bee-toxicity neonicotinoid showed various orientations in bee receptor. [ABSTRACT FROM AUTHOR]

Since its identification as a marker for advanced melanoma in the 1980s, CD146 has been found to have multiple functions in both physiological and pathological processes, including embryonic development, tissue repair and regeneration, tumor progression, fibrosis disease, and inflammations. Subsequent research has revealed that CD146 is involved in various signaling pathways as a receptor or co-receptor in these processes. This correlation between CD146 and multiple diseases has sparked interest in its potential applications in diagnosis, prognosis, and targeted therapy. To better comprehend the versatile roles of CD146, we have summarized its research history and synthesized findings from numerous reports, proposing that cell plasticity serves as the underlying mechanism through which CD146 contributes to development, regeneration, and various diseases. Targeting CD146 would consequently halt cell state shifting during the onset and progression of these related diseases. Therefore, the development of therapy targeting CD146 holds significant practical value., (© 2024. Science China Press.)

Optimizing lanthanide catalyst performance with organic ligands often encounters significant challenges, including susceptibility to water or oxygen and complex synthesis pathways. To address these issues, our research focuses on developing inorganic lanthanide clusters with enhanced stability and functionality. In this study, we introduce the [Sm 6 O(OH) 8 (H 2 O) 24 ]I 8 (H 2 O) 8 cluster (Sm-OC) as a sustainable and efficient catalyst for the aerobic oxidation of thiols under heating conditions. The Sm-OC catalyst demonstrated remarkable stability, outstanding recyclability, and excellent chemoselectivity across a diverse range of functional groups in 38 different tests. Notably, it enables efficient unsymmetrical disulfide synthesis and prevents the formation of over-oxidized by-products, highlighting its superior performance. This Sm-OC catalyst provides a practical and robust tool for the precise construction of versatile disulfides, thus establishing a template for the broader use of lanthanide clusters in organic synthesis., Competing Interests: The authors declare no conflicts of interest.

Oxidation contributes as a secondary driver of the prevailing carbon emission in the chemical industries. To address this issue, photocatalytic aerobic oxidation has emerged as a promising alternative. However, the challenge of achieving satisfactory chemoselectivity and effective use of solar light has hindered progress in this area. In this context, the present study introduces a novel homogeneous photocatalyst, [Sm 6 O(OH) 8 (H 2 O) 24 ]I 8 (H 2 O) 8 cluster (Sm-OC), via a unique auxiliary ligand-free oxidative hydrolysis. Using Sm-OC as catalyst, a solar photocatalyzed aerobic oxidation of thiols has been developed for the synthesis of valuable disulfides. Remarkably, this catalyst manifested a significant turnover number ≥2000 under tested conditions. Sm-OC-catalyzed aerobic oxidation showcased remarkable chemoselectivity. In thiol oxidations, despite the vulnerability of disulfides toward overoxidation, overoxidized byproducts or oxidation of nontarget functional groups was not detected across all 28 tested substrates. This investigation presents the first application of a lanthanide-oxo/hydroxy cluster in photocatalysis.

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1β1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC 50 = 4.40 mg/L) and Myzus persicae (LC 50 = 6.44 mg/L) but also had low toxicity to Apis mellifera . Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

Trehalases (TREs) are pivotal enzymes involved in insect development and reproduction, making them prime targets for pest control. We investigated the inhibitory effect of three thiazolidinones with piperine skeletons (6a, 7b, and 7e) on TRE activity and assessed their impact on the growth and development of the fall armyworm (FAW), Spodoptera frugiperda . The compounds were injected into FAW larvae, while the control group was treated with 2% DMSO solvent. All three compounds effectively inhibited TRE activity, resulting in a significant extension of the pupal development stage. Moreover, the treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormal phenotypes related to growth and development compared to the control group. These results suggest that these TRE inhibitors affect the molting of larvae by regulating the chitin metabolism pathway, ultimately reducing their survival rates. Consequently, these compounds hold potential as environmentally friendly insecticides.

Of ChtI and Of Chi-h are considered potential targets for the control of Asian corn borer ( Ostrinia furnacalis ). In this work, the previously reported Of ChtI inhibitor 5f was found to show certain inhibitory activity against Of Chi-h ( K i = 5.81 μM). Two series of novel butenolide derivatives based on lead compound 5f were designed with the conjugate skeleton, contributing to the π-binding interaction to chitinase, and then synthesized. Compounds 4a-l and 7a-p displayed excellent inhibitory activities against Of ChtI and Of Chi-h, respectively, at a concentration of 10 μM. Compound 4h was found to be a good dual-Chitinase inhibitor, with K i values of 1.82 and 2.00 μM against Of ChtI and Of Chi-h, respectively. The inhibitory mechanism studies by molecular docking suggested that π-π stacking interactions were crucial to the inhibitory activity of novel butenolide derivatives against two different chitinases. A preliminary bioassay indicated that 4h exhibited certain growth inhibition effects against O. furnacalis . Butenolide-like analogues should be further studied as promising novel dual-chitinase inhibitor candidates for the control of O. furnacalis .

To reduce the risk of resistance development, a novel fungicide with dual specificity is demanded. Trehalose is absent in animals, and its synthases, trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), are safe fungicide targets. Here, we report the discovery of a dual-specificity inhibitor of MoTps1 ( Magnaporthe oryzae Tps1, TPS) and MoTps2 ( M. oryzae Tps2, TPP). The inhibitor, named A1-4, was obtained from a virtual screening and subsequent surface plasmon resonance screening. In in vitro assays, A1-4 interacts with MoTps1 and MoTps2-TPP (MoTps2 TPP domain) and inhibits their enzyme activities. In biological activity assays, A1-4 not only inhibits the virulence of M. oryzae on host but also causes aggregation of conidia cytosol, which is a characteristic phenotype of MoTps2 . Furthermore, hydrogen/deuterium exchange mass spectrometry assays support the notion that A1-4 binds to the substrate pockets of TPS and TPP. Collectively, A1-4 is a promising hit compound for the development of safe fungicide with dual-target specificity.

Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions. The Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system of signaling pathways involved in I/R injury. This review article elucidates the underlying mechanisms involved in Wnt signaling, as well as the complex interplay between Wnt and other pathways, including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca 2+ -Activin A, Hippo-Yes-associated protein, toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β, and hepatocyte growth factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, including apoptosis, the inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, and blood-brain barrier damage during I/R injury. Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery, while activation of the non-canonical Wnt pathways exacerbates injury. Moreover, we explore novel therapeutic approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, and clinical trials. The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction, to facilitate the development of innovative therapeutic agents for I/R injury., (© 2023. The Author(s).)

While canonical Wnt signaling is well recognized for its crucial regulatory functions in cell fate decisions, the role of non-canonical Wnt signaling in adult stem cells remains elusive and contradictory. Here, we identified Mcam, a potential member of the non-canonical Wnt signaling, as an important negative regulator of mammary gland epithelial cells (MECs) by genome-scale CRISPR-Cas9 knockout (GeCKO) library screening. Loss of Mcam increases the clonogenicity and regenerative capacity of MECs, and promotes the proliferation, differentiation, and ductal morphogenesis of mammary epithelial in knockout mice. Mechanically, Mcam knockout recruits and polarizes macrophages through the Il4-Stat6 axis, thereby promoting secretion of the non-canonical Wnt ligand Wnt5a and its binding to the non-canonical Wnt signaling receptor Ryk to induce the above phenotypes. These findings reveal Mcam roles in mammary gland development by orchestrating communications between MECs and macrophages via a Wnt5a/Ryk axis, providing evidences for non-canonical Wnt signaling in mammary development., (© 2024. The Author(s).)

Novel agrochemicals have been successfully developed using target-based drug design (TBDD). To discover a novel, efficient, and highly selective nicotinic insecticide candidate, we developed a unified pharmacological model using TBDD by studying the binding modes of 11 nicotinic acetylcholine receptor (nAChR) modulators with acetylcholine binding protein (AChBP) targets for the first time. This model was used to design and develop a series of 1,2,4-triazolone derivatives. Bioassays demonstrated excellent insecticidal activities against Aphis glycines of compounds 4k (LC 50 = 4.95 mg/L) and 4q (LC 50 = 3.17 mg/L), and low toxicities to Apis mellifera . Additionally, compound 4q was stably bound to Aplysia californica AChBP, which was consistent with the pharmacological model obtained via molecular docking and molecular dynamics simulations. Therefore, compound 4q could be a potential lead candidate targeting nAChR. The explicit pharmacological model of nAChR modulators with Ac -AChBP in this study may facilitate the future rational design of eco-friendly nicotinic insecticides.

The application of some reported inhibitors against the chitinolytic enzyme Of ChtI was limited due to their unsatisfactory insecticidal activities. Hence, we first performed a synergetic design strategy combining the π-stacking effect with aqueous solubility to find novel rhodanine analogues with inhibitory activities against Of ChtI. Novel rhodanine compounds IAa-f and IBa-f have weak aqueous solubility, but they ( IAd : K i = 4.0 μM; IBd : K i = 2.2 μM) showed better inhibitory activities against Of ChtI and comparable insecticidal efficiency toward Ostrinia furnacalis compared to the high aqueous solubility compounds IIAa-f and IIBa-f ( IIAd : K i = 21.6 μM; IIBd : K i = 14.3 μM) without a large conjugate plane. Further optimized compounds IIIAa-j with a conjugate plane as well as a higher aqueous solubility exhibited similar good inhibitory activities against Of ChtI ( IIIAe : K i = 2.4 μM) and better insecticidal potency ( IIIAe : mortality rate of 63.33%) compared to compounds IAa-f and IBa-f , respectively. Molecular docking studies indicated that the conjugate planarity with the π-stacking effect for rhodanine analogues is responsible for their enzyme inhibitory activity against Of ChtI. This study provides a new strategy for designing insect chitinolytic enzyme inhibitors as insect growth regulators for pest control.

Trehalase inhibitors prevent trehalase from breaking down trehalose to provide energy. Chitinase inhibitors inhibit chitinase activity affecting insect growth and development. This is an important tool for the investigation of regulation of trehalose metabolism and chitin metabolism in insect reproduction. There are few studies on trehalase or chitinase inhibitors' regulation of insect reproduction. In this study, ZK-PI-5 and ZK-PI-9 were shown to have a significant inhibitory effect on the trehalase, and ZK-PI-9 significantly inhibited chitinase activity in female pupae. We investigated the reproduction regulation of Spodoptera frugiperda using these new inhibitors and evaluated their potential as new insecticides. Compounds ZK-PI-5 and ZK-PI-9 were injected into the female pupae, and the control group was injected with solvent (2% DMSO). The results showed that the emergence failure rate for pupae treated with inhibitors increased dramatically and aberrant phenotypes such as difficulty in wings spreading occurred. The oviposition period and longevity of female adults in the treated group were significantly shorter than those in the control group, and the ovaries developed more slowly and shrank earlier. The egg hatching rate was significantly reduced by treatment with the inhibitor. These results showed that the two new compounds had a significant impact on the physiological indicators related to reproduction of S. frugiperda, and have pest control potential. This study investigated the effect of trehalase and chitin inhibitors on insect reproduction and should promote the development of green and efficient insecticides., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π ‒ π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

As one of the main tumor-infiltrating immune cell types, tumor-associated macrophages (TAMs) determine the efficacy of immunotherapy. However, limited knowledge about their phenotypically and functionally heterogeneous nature restricts their application in tumor immunotherapy. In this study, we identified a subpopulation of CD146 + TAMs that exerted antitumor activity in both human samples and animal models. CD146 expression in TAMs was negatively controlled by STAT3 signaling. Reducing this population of TAMs promoted tumor development by facilitating myeloid-derived suppressor cell recruitment via activation of JNK signaling. Interestingly, CD146 was involved in the NLRP3 inflammasome-mediated activation of macrophages in the tumor microenvironment, partially by inhibiting transmembrane protein 176B (TMEM176B), an immunoregulatory cation channel. Treatment with a TMEM176B inhibitor enhanced the antitumor activity of CD146 + TAMs. These data reveal a crucial antitumor role of CD146 + TAMs and highlight the promising immunotherapeutic approach of inhibiting CD146 and TMEM176B., (© 2023. The Author(s).)

Introduction: Spodoptera frugiperda is an omnivorous agricultural pest which is great dangerous for grain output. Methods: In order to investigate the effects of potential trehalase inhibitors, ZK-PI-5 and ZK-PI-9, on the growth and development of S. frugiperda , and to identify new avenues for S. frugiperda control, we measured the content of the trehalose, glucose, glycogen and chitin, enzyme activity, and gene expression levels in trehalose and chitin metabolism of S. frugiperda . Besides, their growth and development were also observed. Results: The results showed that ZK-PI-9 significantly reduced trehalase activity and ZK-PI-5 significantly reduced membraned-bound trehalase activity. Moreover, ZK-PI-5 inhibited the expression of SfTRE2, SfCHS2, and SfCHT , thus affecting the chitin metabolism. In addition, the mortality of S. frugiperda in pupal stage and eclosion stage increased significantly after treatment with ZK-PI-5 and ZK-PI-9, which affected their development stage and caused death phenotype (abnormal pupation and difficulty in breaking pupa). Discussion: These results have provided a theoretical basis for the application of trehalase inhibitors in the control of agricultural pests to promote future global grain yield., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Yu, Jiang, Chen, Wang, Chao, Jiang, He, Xu, Wang, Tang, Duan and Wu.)

Background: The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of ROSE during the EUBS-TBNA procedure in the diagnosis of pulmonary lesions (PLs)., Methods: Enrolled in this study were 260 patients with nodules, masses, cavities, or inflammatory lesions on pulmonary CT images. They were assigned to undergo EBUS-TBNA with ROSE ( n = 134) or without ROSE ( n = 126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we further explored whether the ROSE method during EBUS-TBNA would improve the diagnostic yield and reduce the incidence of complications., Results: The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE and the non-ROSE group were 29.9 and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of the ROSE method during EBUS-TBNA were 97.4, 96.9, 92.5, and 98.90%, respectively. The result of the chi-square test effectively proved that ROSE operation during EBUS-TBNA contributes to the diagnosis of malignancy compared with the non-ROSE group (χ 2 = 13.858, P < 0.001). The number of punctures in the ROSE group was significantly lower than that in the non-ROSE group ( P < 0.001)., Conclusion: ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield of malignant diseases compared with the non-ROSE group and reduce the number of intraoperative punctures, which is a clinical application worth popularizing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, Duan, Zhu, Yang, Li, Wang and Xie.)

Odorant-binding protein (OBP) is a potential target for developing insect behavior control agents due to its properties in transporting semiochemicals. In this study, 12 novel jasmonic acid (JA) derivatives were rationally designed and synthesized based on the binding features between Acyrthosiphon pisum OBP3 (ApisOBP3) and compound D1 [( E )-3,7-dimethylocta-2,6-dien-1-yl 2-(3-oxo-2-pentylcyclopentyl)acetate] with a binding affinity ( K d ) of 26.79 μM. Most novel JA derivatives displayed better binding affinities than D1 ( K d = 1-26 μM). Among them, compound 6b [( E )-3,7-dimethylocta-2,6-dien-1-yl-2-(( Z )-3-((acryloyloxy)imino)-2-pentylcyclopentyl)acetate] is the most promising compound with an excellent K d of 1.33 μM and a significant repellent activity with repellent rates of 50-60% against A. pisum and Myzus persicae . Both hydrophobic and electrostatic interactions were found to contribute significantly to the binding of 6b to ApisOBP3. This study provides significant guidance for the rational design and efficient identification of novel aphid repellents based on aphid OBPs.

Asian corn borer ( Ostrinia furnacalis ) is one of the most destructive pests in agriculture. Three chitinases Of ChtI, Of ChtII, and Of Chi-h are regarded as potential targets for discovering novel agrochemicals to control O. furnacalis . In this study, piperine ( K i = 43.78∼83.03 μM) was first shown to exhibit inhibitory activities against all three chitinases. Subsequently, 19 novel piperine derivatives were rationally designed based on the conserved aromatic residues of three chitinases and then synthesized. Among them, Compound 5k ( K i = 11.78∼22.82 μM) was identified as the most effective multichitinase inhibitor and indeed displayed higher insecticidal activity against O. furnacalis than dual- or single-chitinase inhibitors. Molecular mechanism studies clarified that Compound 5k interacted with two conserved TRP and TYR of three chitinases in identical modes through hydrogen bonds, hydrophobic, and π-π interactions. Moreover, the microinjection experiment indicated that Compound 5k exhibited substantial sublethal effects against O. furnacalis by regulating its growth and development. This study provides evidence of multichitinase inhibitors to be applied in the control of O. furnacalis .

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Initiation of T cell receptor (TCR) signaling involves the activation of the tyrosine kinase LCK; however, it is currently unclear how LCK is recruited and activated. Here, we have identified the membrane protein CD146 as an essential member of the TCR network for LCK activation. CD146 deficiency in T cells substantially impaired thymocyte development and peripheral activation, both of which depend on TCR signaling. CD146 was found to directly interact with the SH3 domain of coreceptor-free LCK via its cytoplasmic domain. Interestingly, we found CD146 to be present in both monomeric and dimeric forms in T cells, with the dimerized form increasing after TCR ligation. Increased dimerized CD146 recruited LCK and promoted LCK autophosphorylation. In tumor models, CD146 deficiency dramatically impaired the antitumor response of T cells. Together, our data reveal an LCK activation mechanism for TCR initiation. We also underscore a rational intervention based on CD146 for tumor immunotherapy.

Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies., (© 2020. CSI and USTC.)

The outbreak of SARS-coronavirus 2 (SARS-CoV2) has become a global health emergency. Although enormous efforts have been made, there is still no effective treatment against the new virus. Herein, a TiO 2 supported single-atom nanozyme containing atomically dispersed Ag atoms (Ag-TiO 2 SAN) is designed to serve as a highly efficient antiviral nanomaterial. Compared with traditional nano-TiO 2 and Ag, Ag-TiO 2 SAN exhibits higher adsorption (99.65%) of SARS-CoV2 pseudovirus. This adsorption ability is due to the interaction between SAN and receptor binding domain (RBD) of spike 1 protein of SARS-CoV2. Theoretical calculation and experimental evidences indicate that the Ag atoms of SAN strongly bind to cysteine and asparagine, which are the most abundant amino acids on the surface of spike 1 RBD. After binding to the virus, the SAN/virus complex is typically phagocytosed by macrophages and colocalized with lysosomes. Interestingly, Ag-TiO 2 SAN possesses high peroxidase-like activity responsible for reactive oxygen species production under acid conditions. The highly acidic microenvironment of lysosomes could favor oxygen reduction reaction process to eliminate the virus. With hACE2 transgenic mice, Ag-TiO 2 SAN showed efficient anti-SARS-CoV2 pseudovirus activity. In conclusion, Ag-TiO 2 SAN is a promising nanomaterial to achieve effective antiviral effects for SARS-CoV2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Spray cryotherapy (SCT) is a new transbronchial approach that disrupts epithelial cells by freezing. However, there are limited data addressing the effect of SCT on airway secretion. The aim of this study was to evaluate if SCT effect on airway secretion and the possible mechanism in canines. Fifteen labradors were randomly scheduled SCT or sham operation. Six labradors were scheduled SCT for a short-time observation, and six for a long-time observation, the remaining three received sham operation as control. Lung tissues were harvested for PAS staining. Mucin, MUC5AC and acetylcholine in bronchoalveolar lavage fluid (BALF) were analyzed by enzyme-linked immunosorbent assay (ELISA). CHRM3 and Mucin 5AC (MUC5AC) expressions in the lung tissues were analyzed by immunohistochemistry. MUC5AC mRNA expression was analyzed by rt-PCR. From 0 day to 30 days after SCT, the ratio of PAS positive cells to total bronchial epithelial cells, the average optical density of MUC5AC + by immunohistochemistry, the protein expression of MUC5AC, acetylcholine in BALF decreased compared with that of control group (p < 0.05). The average optical density of CHRM3+ by immunohistochemistry were decreased from 0 day to 7 days after SCT (p < 0.05) compared with control group. In conclusion, SCT was able to reduce the PAS-, MUC5AC- and CHRM3-positive cells in the lung tissue and acetylcholine in BALF, suggesting that SCT may prove to be a beneficial way in mucus excessive production in airway and acetylcholine-CHRM3 pathway may one possible mechanism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

CD146 is an adhesion molecule that plays important roles in angiogenesis, cancer metastasis, and immune response. It exists as a monomer or dimer on the cell surface. AA98 is a monoclonal antibody that binds to CD146, which abrogates the activation of CD146-mediated signaling pathways and shows inhibitory effects on tumor growth. However, how AA98 inhibits the function of CD146 remains unclear. Here, we describe a crystal structure of the CD146/AA98 Fab complex at a resolution of 2.8 Å. Monomeric CD146 is stabilized by AA98 Fab binding to the junction region of CD146 domains 4 and 5. A higher-affinity AA98 variant (here named HA98) was thus rationally designed. Better binding to CD146 and prominent inhibition on cell migration were achieved with HA98. Further experiments on xenografted melanoma in mice with HA98 revealed superior inhibitory effects on tumor growth to those of AA98, which suggested future applications of this antibody in cancer therapy., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients., Methods: 109 adult patients were enrolled in our study in Shanghai Tenth People's Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed., Results: 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS., Conclusions: The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.

The current COVID-19 pandemic is not only a threat to physical health, but also brings a burden to mental health in the general Chinese population. However, the temporal change of mental health status due to pandemic-related stress in relation to protective and risk factors to hostility is less known. This study was implemented at two timepoints, i.e., during the peak and the remission of the COVID-19 pandemic. 3233 Chinese individuals participated in the first wave, and among them 1390 participants were followed in a second wave. The result showed that fear significantly decreased over time, while depression level significantly increased during the second wave compared to the first wave of the survey. Younger age, lower-income, increased level of perceived stress, and current quarantine experience were significant predictors of depression escalation. Younger people and individuals who had a higher initial stress response tended to show more hostility. Furthermore, the use of negative coping strategy plays a potential intermediating role in the stress-related increase in hostility, while social support acts as a buffer in hostility in the general population under high stress. As the whole world is facing the same pandemic, this research provides several implications for public mental health intervention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To investigate the effectiveness of Liuzijue exercise on chronic obstructive pulmonary disease (COPD) in the stable phase., Methods: We searched six electronic bibliographic databases (PubMed, EMBASE, The Cochrane Library, Web of Science, CNKI, and Wan Fang Data) from inception to August 2018. Randomized controlled trials (RCTs) were included if they evaluated the effect of Liuzijue exercise on stable COPD. Cochrane Collaboration risk-of-bias tool (Cochrane Handbook 5.1.0) was used to assess the risk of bias of included RCTs. Meta-analysis was performed using the Review Manager software (RevMan V.5.3.5) provided by the Cochrane Collaboration. Outcomes assessed included dyspnea, exercise capacity, lung function, and quality of life., Results: Fourteen RCTs involving 920 stable COPD patients were included in this systematic review and meta-analysis. The control groups received usual care. The average number of training sessions per participant was 9.3 per week, and the average length of these training sessions was 31.6 min per week. Training duration varied from 3 to 12 months. Meta-analysis results showed that Liuzijue exercise can effectively improve patients' Modified Medical Research Council Dyspnea Scale scores (MD = - 0.73, 95% CI: - 1.13 to - 0.33, P < 0.05), 6MWD (MD = 17.78, 95% CI: 7.97 to 27.58, P < 0.05), forced expiratory volume in one second (FEV 1 ) (MD = 0.23, 95% CI: 0.07 to 0.38, P < 0.05), the percentage of predicted values of FEV 1 (FEV 1 %pred) (MD = 7.59, 95% CI: 2.92 to 12.26, P < 0.05), FEV 1 /FVC (Forced vital capacity) ratio (MD = 6.81, 95% CI: 3.22 to 10.40, P < 0.05), Quality of life: St. George's Respiratory Questionnaire total score (MD = - 9.85, 95%CI: - 13.13 to - 6.56, P < 0.05), and Chronic Obstructive Pulmonary Disease Assessment Test score (MD = - 2.29, 95%CI: - 3.27, - 1.30, P < 0.05)., Conclusion: Evidence from meta-analysis suggested that Liuzijue exercise could improve dyspnea, exercise endurance, lung function, and quality of life for stable COPD patients. However, owing to the methodological bias and the placebo effect of Liuzijue exercise, there is a need for further research to confirm these findings., Trial Registration: PROSPERO (ID: CRD42019130973 ).

Background: The aim of this study was to investigate the optimal order of radiation therapy in patients affected by stage IIIA pathologic N2 (IIIA/N2) non-small-cell lung cancer (NSCLC) and to identify its potential risk factors., Methods: 17,654 (8786 men and 8868 women) diagnosed with NSCLC stage IIIA-N2 from 2004 to 2015 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Among the relevant clinical parameters, we evaluated overall survival (OS), lung cancer-specific survival (LCSS) and other variables such as age, sex and tumor size in patients who were treated with different combinations of surgery and radiotherapy strategies., Results: We discovered that surgery benefit in younger IIIA/N2 NSCLC patients (age ≤ 75), and compared with surgery only, preoperative radiotherapy significantly improved the survival rate most (p < 0.001). When we performed the OS and LCSS analysis in the subgroup of patients' age > 75 years old, who underwent postoperative radiotherapy (PORT) had the highest survival rate (p < 0.001). Multivariate analyses showed that the following parameters had a negative impact on survival: female sex, older age, no chemotherapy, large tumor size, high tumor grade, no surgery or radiotherapy., Conclusions: In IIIA/N2 NSCLC patients, surgery, radiotherapy and chemotherapy were associated with improved OS and LCSS. Younger patients underwent surgical resection and chemotherapy, the main population we studied, benefited most from preoperative radiotherapy in all orders with radiation therapy (p < 0.001). In patients more than 75 years old, there was no clear benefit from only surgery, and PORT was recommended in case of having surgery.

Motivation can be generated intrinsically or extrinsically, and both kinds of motivation show similar facilitatory effects on memory. However, effects of extrinsic and intrinsic motivation on memory formation have not been studied in combination and thus, it is unknown whether they interact and how such interplay is neurally implemented. In the present study, both extrinsic monetary reward and intrinsic curiosity enhanced memory performance, without evidence for an interaction. Functional magnetic resonance imaging revealed that curiosity-driven activity in the ventral striatal reward network appears to work cooperatively with the fronto-parietal attention network, while enhancing memory formation. In contrast, the monetary reward-modulated subsequent memory effect revealed deactivation in parietal midline regions. Thus, curiosity might enhance memory performance by allocation of attentional resources and reward-related processes; while, monetary reward does so by suppression of task-irrelevant processing.

Altered anticipation processes are implicated across various clinical samples, but few studies focused on the posttraumatic stress disorder (PTSD). We measured contingent negative variation (CNV) in a choice reaction paradigm among 58 survivors of the Wenchuan earthquake, including 28 individuals who were diagnosed with PTSD and 30 without PTSD. Compared to the non-PTSD group, the PTSD group had significantly larger CNV amplitude. On the behavioral level, although the reaction times were comparable between groups, the PTSD group committed more errors than the non-PTSD group. Furthermore, the total PTSD symptom severity score as well as the re-experiencing symptom score were positively related to CNV amplitude. These results suggested that individuals with PTSD might be more alerted to and anticipate more to upcoming events in their environment, yet still have degraded performance in response to the stimulus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

It is well known that preparing for and taking high-stakes exams has a significant influence on the emotional and physiological wellbeing of exam-takers, but few studies have investigated the resulting cognitive changes. The current study examined the effect of examination-induced academic stress on anticipation in information processing. Anticipation was indexed using the contingent negative variation (CNV). Electroencephalograms (EEG) were collected from 42 participants using the classic S1-S2 paradigm. These participants were preparing for the Chinese National Postgraduate Entrance Exam (NPEE). EEGs were also collected from 21 age-matched, non-exam comparison participants. The levels of perceived stress and state anxiety were higher and both the initial CNV (iCNV) and the late CNV (lCNV) were more negative in the exam group than in the non-exam group. These results suggest that participants under academic stress experienced greater anticipation of upcoming events. More important, for the non-exam group, state anxiety was positively related to both the iCNV and lCNV amplitude, and this correlation existed when trait anxiety was controlled; however, there was no such relationship in the exam group. These results suggested that the cortical anticipatory activity in the high-stressed exam group reached the maximum ceiling, leaving little room for transient increases in state anxiety., (Copyright © 2015 Elsevier Inc. All rights reserved.)

As opposed to humans, insects rely heavily on an acute olfactory system for survival and reproduction. Two major types of olfactory proteins, namely, odorant-binding proteins (OBPs) and odorant receptors (ORs), may contribute to the selectivity and sensitivity of the insects' olfactory system. Here, we aimed at addressing the question whether OBPs highly enriched in the antennae of the southern house mosquito, Culex quinquefasciatus, contribute at least in part to the selective reception of physiologically relevant compounds. Using a fluorescence reporter and a panel of 34 compounds, including oviposition attractants, human-derived attractants, and repellents, we measured binding affinities of CquiOBP1, CquiOBP2, and CquiOBP5. Based on dissociation constants, we surmised that CquiOBP2 is a carrier for the oviposition attractant skatole, whereas CquiOBP1 and CquiOBP5 might transport the oviposition pheromone MOP, a human-derived attractant nonanal, and the insect repellent picardin. Binding of these three ligands to CquiOBP1 was further analyzed by examining the influence of pH on apparent affinity as well as by docking these three ligands into CquiOBP1. Our findings suggest that CquiOBP1 might discriminate MOP from nonanal/picaridin on the basis of the midpoint transition of a pH-dependence conformational change, and that MOP is better accommodated in the binding cavity than the other two ligands. These findings, along with previous experimental evidence suggesting that CquiOBP1 does not detect nonanal in vivo, suggest that OBP selectivity may not be clearly manifested in their dissociation constants.

Objective: To explore the relationship between circulating level of soluble CD146 (sCD146) and plaque vulnerability or inflammatory factors in patients with carotid atherosclerosis (CAS)., Methods: Forty CAS patients with carotid stenosis ( ≥ 70%) were enrolled and divided into 2 groups of stable and unstable plaque by ultrasonic imaging. And another 40 healthy subjects were enrolled for control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to measure the serum levels of sCD146 and matrix metalloproteinase-9 (MMP-9), analyze the correlation of sCD146 with MMP-9 and high sensitivity CRP (hs-CRP), and evaluate whether sCD146 correlates with plaque vulnerability., Results: Soluble CD146 level was elevated in CAS patients versus healthy donors [(212 ± 43) vs (173 ± 36) ng/ml, P < 0.001]. And sCD146 level significantly increased in CAS patients with unstable plaques than those with stable plaque [(218 ± 28) vs (176 ± 25) ng/ml, P < 0.001]. And sCD146 was correlated with high-sensitivity C-reactive protein (hsCRP, r = 0.370 9, P = 0.018 5), a well-known marker for CAS inflammation. Also it was an independent risk factor for plaque vulnerability (OR = 1.16, 95%CI:1.020-1.310, P = 0.019 2). And its level was not correlated with the risk factors of CAS, such as age, homocysteine, triglyceride, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) or high density lipoprotein-cholesterol (HDL-C) (P > 0.05). But there was a good correlation with the serum level of MMP-9 in CAS patients (r = 0.677 2, P < 0.001)., Conclusion: The concentration of soluble CD146 is positively correlated with hsCRP and MMP-9 in CAS patients. And inflammation and neovascularization may interact with each other during atherosclerotic process. The serum level of sCD146 is correlated independently with plaque vulnerability.

Objective: To investigate the correlation between the expression of adhesion molecule CD146 and the vulnerability of carotid atherosclerotic plaque., Methods: The plaque samples were collected from 40 patients who underwent the carotid endarterectomy and were divided into the stable plaque group and the instable plaque group by ultrasound imaging. Five carotid artery samples were taken from the healthy donors as the control. Immunohistochemistry was applied to test the CD146 expression in all samples., Results: Higher expression of CD146 was observed in the atherosclerotic plaques than in the healthy control. Moreover, statistical difference was found in the expression of CD146 in the plaques between the instable plaque group and the stable plaque group (0.31 ± 0.19 vs 0.17 ± 0.07, P < 0.05). The expression of CD146 was positively correlated with the necrotic area (r = 0.471 8, P = 0.019 9) and the matrix metalloproteinase (MMP)-9 expression in the plaques (r = 0.535 6, P = 0.000 9)., Conclusion: The CD146 expression is correlated with the vulnerability of carotid atherosclerotic plaque.

Nitrogen clusters have been intensively studied for their potential application as high-energy density materials, but a six-membered nitrogen ring (N6) was not found to be stable and aromatic. To explore the possibility of inducing an aromatic N6 ring via cation-pi interaction, quantum chemistry calculations were performed on the systems of Ca2N6, CaN6, CaN6(2-), N6, and N6(4-) at the B3LYP/6-311+G level. The optimized geometries reveal that the planar structure of the N6 ring is stable only in the Ca2N6 complex. The computed NBO and CHelpG charges demonstrate that the planar N6 moiety in the Ca2N6 complex is almost a 10pi-electron system. The predicted nucleus-independent chemical shift (NICS) values demonstrate that the N6 moiety is aromatic in comparison with the NICS values of benzene. The estimated enthalpy of formation for the Ca2N6 complex is 100.4 kcal/mol for the reaction of 2Ca and 3N2. The binding energy between the Ca2+ cation and the N6(4-) moiety is -1928.8 kcal/mol, with electrostatic interaction serving as the predominant component. When all the calculated results are taken into account, including the planar structure, 10pi-electron system, identical bond length, and negative NICS value of the N6(4-) moiety in the Ca2N6 complex, it is deduced that the alkaline earth metal Ca is capable of inducing an aromatic N6 ring through the cation-pi interaction formed by electron transfer from the Ca atom to the N6 ring.