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Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain. • Forsythiaside B ameliorates complete Freund's adjuvant (CFA) induced thermal hypersensitivity and mechanical allodynia. • Forsythiaside B exerts anxiolytic effects in CFA-injected mice. • Forsythiaside B decreases CFA-induced proinflammatory cytokines level in the spinal cord. • Forsythiaside B attenuates CFA-triggered microglia and astrocyte activation in the spinal cord. [ABSTRACT FROM AUTHOR]

Environmental xenobiotics can influence the tolerance of insects to chemical insecticides. Heavy metals are widespread distributed, can be easily bio-accumulated in plants and subsequently within phytophagous insects via the food chains. However, less attention has been paid to the effect of heavy metal exposure on their insecticide tolerance. In this study, pre-exposure of copper (Cu, 25–100 mg kg−1) significantly enhanced the subsequent tolerance of Spodoptera litura to β-cypermethrin, a widely used pyrethroid insecticide in crop field. Cytochrome P450 monooxygenases (CYPs) activities were cross-induced in larvae exposed to Cu and β-cypermethrin, while the activities of glutathione S-transferase (GST) and carboxylesterase (CarE) were not affected. Application of piperonyl butoxide (PBO), a P450 synergist, effectively impaired the tolerance to β-cypermethrin in Cu-exposed S. litura larvae with a synergistic ratio of 1.72, indicating that P450s contribute to larval tolerance to β-cypermethrin induced by Cu exposure. Among the four CYP6AB family genes examined, only larval midgut-specific CYP6AB12 was found to be cross-induced by Cu and β-cypermethrin. RNA interference (RNAi)-mediated silencing of CYP6AB12 effectively decreased the mRNA levels of the target gene, and significantly reduced the larval tolerance to β-cypermethrin following exposure to Cu. These results showed that pre-exposure of heavy metal Cu enhanced larval tolerance to β-cypermethrin in S. litura , possibly through the cross-induction of P450s. Our findings provide new insights on the relationship between heavy metals and chemical insecticides that may benefit both the risk evaluation of heavy metal contamination and development of pest management strategies. Unlabelled Image • Cu exposure enhanced the subsequent tolerance of Spodoptera litura to β-cypermethrin. • P450 activities were cross-induced in larvae exposed to Cu and β-cypermethrin. • RNAi was used to study the functions of SlCYP6AB12. • Cu-induced up-regulation of SlCYP6AB12 enhanced the larval tolerance to β-cypermethrin. [ABSTRACT FROM AUTHOR]

Little seems to be known about heteroclinic cycles and chaos in three-dimensional piecewise smooth dynamical systems with two or more discontinuous boundaries. This article presents a new class of three-dimensional three-zone piecewise affine systems with two discontinuous boundaries and provides some criteria for the existence of heteroclinic cycles in the following cases: (i) one saddle point and two focus points, (ii) two saddle points and one focus point, and (iii) three saddle points. Moreover, sufficient conditions for the existence of chaos are established. Finally, two numerical examples are provided to show the feasibility of our theoretical approach. [ABSTRACT FROM AUTHOR]

In the plant-insect arms race, plants synthesize toxic compounds to defend against herbivorous insects, whereas insects employ cytochrome P450 monooxygenases (P450s) to detoxify these phytotoxins. As ubiquitous environmental contaminants, heavy metals can be easily absorbed by plants and further accumulated in herbivorous insects through the food chains, resulting in tangible consequences for plant-insect interactions. However, whether heavy metals can influence P450 activities and thereby cause further effects on larval tolerance to phytotoxins remains unknown. In this study, we shown that prior exposure to copper (Cu) enhanced larval tolerance to xanthotoxin in Spodoptera litura , a major polyphagous pest of agriculture. P450 activities were induced in larvae exposed to Cu or xanthotoxin, and a midgut specific expressed P450 gene, CYP6B50 was cross-induced after exposure to these two toxic xenobiotics. Knocking down CYP6B50 by RNA interference (RNAi) rendered the larvae more sensitive to xanthotoxin. As defense against oxidative stress following metal exposure has been demonstrated to affect insecticide resistance, the reactive oxygen species (ROS) generation and antioxidant enzyme activities were assessed. Cu exposure caused the accumulation of hydrogen peroxide (H 2 O 2) and enhanced the activities of superoxide dismutase (SOD) and peroxidase (POD) in larval midgut. In addition, two antioxidant response elements (AREs) were identified from the CYP6B50 promoter, indicating that Cu-induced CYP6B50 expression may be related to the ROS burst. Application of ROS scavenger N -acetylcysteine (NAC) effectively suppressed CYP6B50 expression, inhibited P450 activities and impaired larval tolerance to xanthotoxin that had been induced by Cu. These results indicate that the increase in CYP6B50 expression regulated by Cu-induced H 2 O 2 generation contributed to the enhancement of larval tolerance to xanthotoxin in S. litura. Ingestion of heavy metals from their host plants can inadvertently boost the counter-defense system of herbivorous insects to protect themselves against plant defensive toxins. Unlabelled Image • Prior exposure to Cu enhanced larval tolerance to xanthotoxin in Spodoptera litura. • CYP6B50 expression was cross-induced by Cu and xanthotoxin. • Cu pexposure stimulated H 2 O 2 generation and enhanced antioxidant enzyme activity. • NAC suppressed CYP6B50 expression and impaired larval tolerance to xanthotoxin. [ABSTRACT FROM AUTHOR]

To improve the computing efficiency and precision of probabilistic design for multi-failure structure, a distributed collaborative probabilistic design method-based fuzzy neural network of regression (FR) (called as DCFRM) is proposed with the integration of distributed collaborative response surface method and fuzzy neural network regression model. The mathematical model of DCFRM is established and the probabilistic design idea with DCFRM is introduced. The probabilistic analysis of turbine blisk involving multi-failure modes (deformation failure, stress failure and strain failure) was investigated by considering fluid–structure interaction with the proposed method. The distribution characteristics, reliability degree, and sensitivity degree of each failure mode and overall failure mode on turbine blisk are obtained, which provides a useful reference for improving the performance and reliability of aeroengine. Through the comparison of methods shows that the DCFRM reshapes the probability of probabilistic analysis for multi-failure structure and improves the computing efficiency while keeping acceptable computational precision. Moreover, the proposed method offers a useful insight for reliability-based design optimization of multi-failure structure and thereby also enriches the theory and method of mechanical reliability design. [ABSTRACT FROM AUTHOR]

The brown planthopper, Nilaparvata lugens , possesses a strong adaptability to extreme temperature and insecticide stresses. Heat shock proteins (Hsps) are highly conserved molecular chaperones and play a pivotal role in response to various environmental stresses in insects. However, little is known about the response of Hsps to stresses in N. lugens . In the present study, an inducible Hsp70 ( Nl Hsp70) was isolated from this insect and transcriptional expression patterns of NlHsp70 under temperature and insecticide stresses were analyzed. The full-length of NlHsp70 was 2805 bp with an open reading frame (ORF) of 1896 bp, showing high homology to its counterparts in other species. Expression of NlHsp70 was not altered by heat shock for 1 h, nor following recovery from thermal stress. Conversely, decreased expression of NlHsp70 was observed in response to cold shock. In addition, the expression of NlHsp70 increased after imidacloprid exposure. RNA interference experiment combined with insecticide injury assay also demonstrated that NlHsp70 was essential for resistance against insecticide exposure. These observations indicated that NlHsp70 was an important gene involved in the resistance or tolerance to environmental stresses in N. lugens . Interestingly, weak changes in mRNA expression levels of two thermal-inducible Hsp genes, NlHsp90 and NlHsc70 were observed in imidacloprid-exposed N. lugens adults, suggesting that different Hsps may respond differential to the extreme temperature and insecticide stresses. [ABSTRACT FROM AUTHOR]

The involvement of carboxylesterases (CarEs) in resistance to chlorpyrifos has been confirmed by the synergism analysis in Nilaparvata lugens. However, the function of specific CarE gene in chlorpyrifos resistance and the transcriptional regulatory mechanism are obscure. Herein, the expression patterns of 29 CarE genes in the susceptible and chlorpyrifos-resistant strains were analyzed. Among them, CarE3 , CarE17 and CarE19 were overexpressed in the resistant strain, and knockdown of either CarE gene by RNA interference significantly increased the susceptibility to chlorpyrifos. Remarkably, knockdown of CarE17 reduced the enzymatic activity of CarE by 88.63 % and showed a much greater effect on increasing chlorpyrifos toxicity than silencing other two CarE genes. Overexpression of CarE17 in Drosophila melanogaster decreased the toxicity of chlorpyrifos to transgenic fruit flies. Furthermore, the region between − 205 to + 256 of CarE17 promoter sequence showed the highest promoter activity, and 16 transcription factors (TFs) were predicted from this region. Among these TFs, Lim1β and C15 were overexpressed in the resistant strain. Knockdown of either TF resulted in reduced CarE17 expression and a decrease in resistance of N. lugens to chlorpyrifos. These results indicate that the constitutive overexpression of Lim1β and C15 induces CarE17 expression thus conferring chlorpyrifos resistance in N. lugens. • Three CarE genes were involved in chlorpyrifos resistance of N. lugens. • Metabolic resistance of N. lugens to chlorpyrifos is extremely attributed to CarE17. • Potential binding sites for homeobox TFs were predicted from CarE17 promoter. • Lim1β and C15 induces CarE17 expression thus increasing chlorpyrifos resistance. [ABSTRACT FROM AUTHOR]

Abstract: Multi-threaded programs on shared-memory hardware tend to be non-deterministic, which brings challenges to software debugging and testing. Current deterministic implementations eliminate nondeterminism of multi-threaded programs by trading much parallelism for determinism, which leads to low performance. Researchers typically improve parallelism by weakening determinism or introducing weak memory consistency models. However, weak determinism cannot deal with non-determinism caused by data races which are very common in multi-threaded programs. Weak memory consistency models impact the productivity of programming and may bring correctness problems of legacy programs. To address the problems, this paper presents a fully parallelized deterministic runtime, FPDet, which exploits parallelism of deterministic multi-threaded programs by preserving strong determinism and sequential memory consistency. FPDet creates a Working Set Memory (WSM) for each thread to make threads run independently for parallelism. FPDet guarantees determinism by redistributing memory blocks among threads’ WSMs in specified synchronization points. As a result, FPDet obtains parallelism and determinism simultaneously. To further exploit parallelism, we propose an Adaptive Budget Adjustment (ABA) mechanism to minimize wait time caused by thread synchronization. We evaluated FPDet using benchmarks from both the SPLASH-2 and PARSEC suits. The results show that FPDet can effectively improve parallelism (the average speedup is more than 1.4 compared with existing approaches) without weakening determinism or memory consistency. [Copyright &y& Elsevier]

Abstract: Load balancing has been a key concern for traditional multiprocessor systems. The emergence of computational grids extends this challenge to deal with more serious problems, such as scalability, heterogeneity of computing resources and considerable transfer delay. In this paper, we present a dynamic and decentralized load balancing algorithm for computationally intensive jobs on a heterogeneous distributed computing platform. The time spent by a job in the system is considered as the main issue that needs to be minimized. Our main contributions are: (1) Our algorithm uses site desirability for processing power and transfer delay to guide load assignment and redistribution, (2) Our transfer and location policies are a combination of two specific strategies that are performance driven to minimize execution cost. These two policies are the Instantaneous Distribution Policy (IDP) and the Load Adjustment Policy (LAP), (3) The communication overhead involved in information collection is reduced using mutual information feedback. The simulation results show that our proposed algorithm outperforms conventional approaches over a wide range of system parameters. [Copyright &y& Elsevier]

Increased production of detoxification enzymes appears to be the primary route for insecticide resistance in many crop pests. However, the mechanisms employed by resistant insects for overexpression of detoxification genes involved in insecticide resistance remain obscure. We report here that the NR2E nuclear receptor HR83 plays a critical role in chlorpyrifos resistance by regulating the expression of detoxification genes in the brown planthopper (BPH), Nilaparvata lugens. HR83 was highly expressed in the fat body and ovary of adult females in chlorpyrifos-resistant BPHs. Knockdown of HR83 by RNA interference showed no effect on female fecundity, whereas caused a decrease of resistance to chlorpyrifos. This treatment also led to a dramatic reduction in the expression of multiple detoxification genes, including four UDP-glycosyltransferases (UGTs), three cytochrome P450 monooxygenases (P450s) and four carboxylesterases (CarEs). Among these HR83 -regulated genes, UGT-1-3 , UGT-2B10 , CYP6CW1 , CYP4CE1 , CarE and Esterase E4-1 were over-expressed both in the fat body and ovary of the resistant BPHs. Functional analyses revealed that UGT-2B10 , CYP4CE1 , CarE and Esterase E4-1 are essential for the resistance of BPH to chlorpyrifos. Generally, this study implicates HR83 in the metabolic detoxification–mediated chlorpyrifos resistance and suggests that the regulation of detoxification genes may be an ancestral function of the NR2E nuclear receptor subfamily. [Display omitted] • HR83 was highly expressed in chlorpyrifos-resistant BPHs. • Knockdown of HR83 decreased the resistance of BPH to chlorpyrifos. • HR83 was involved in the regulation of the expression of multiple detoxification genes. • HR83 -affected UGT-2B10 and CYP4CE1 were associated with chlorpyrifos resistance. [ABSTRACT FROM AUTHOR]

Concurrent construction of robust SEI and CEI enriched with pyrrole/Ppy-analogues to achieve dendrite-free Zn anodes and enhance cathode capacity and stability towards advanced aqueous zinc-ion batteries. [Display omitted] • The pyrrole-based solid electrolyte interphase (SEI) guides uniform Zn2+ deposition and suppresses HER and side reactions. • A dendrite-free zinc anode is achieved with a prolonged cycle life of over 6000 h in Zn//Zn cell at 0.5 mA/cm2. • The cathode electrolyte interphase (CEI) comprising polypyrrole analogues achieves enhanced cathode capacity and stability for both PANI and MnO 2. The advancement of aqueous zinc-ion batteries (AZIBs) is impeded by challenges encompassing cathodic and anodic aspects, such as limited capacity and dendrite formation, constraining their broader utilization. Herein, pyrrole, an economically viable and readily accessible compound, is proposed as a versatile electrolyte additive to address these challenges. Experiments and DFT calculations reveal that pyrrole and its derivatives preferentially adsorb onto zinc foil, facilitating the formation of a pyrrole-based solid electrolyte interphase (SEI), which effectively guides uniform Zn2+ deposition through strong attraction force and suppresses hydrogen evolution reactions and parasitic reactions. On the cathode side, the additive promotes the formation of a durable cathode electrolyte interphase (CEI) enriched with poly-pyrrole (Ppy) analogues. Such layer significantly contributes to extra capacity of both polyaniline (PANI) and MnO 2 cathodes by leveraging the electrochemical reactivity of Ppy towards Zn2+ and improves their cyclic stability. Consequently, a dendrite-free Zn anode is realized with an extended cyclic lifespan surpassing 6000 h in Zn//Zn cell, coupled with an average Coulombic efficiency of 99.7 % in Cu//Zn cell. Moreover, the PANI//Zn and MnO 2 //Zn full cells demonstrate enhanced capacities along with improved cycling stability. This work provides a new additive strategy towards concurrent stabilization of cathode and Zn anode in AZIBs. [ABSTRACT FROM AUTHOR]

Limited efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC) was observed in clinical trials, thus prompting investigation into combination therapy. Interleukin-6 (IL-6) has important roles in modeling immune responses in cancers. Here, we hypothesized that IL-6 blockade would enhance antitumor immunity of HCC and synergize with anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor in treating HCC. The sources and immune modulating effects of IL-6 were investigated in HCC models. Combination of anti-IL-6 and anti-PD-L1 was tested in HCC bearing mice. We found that IL-6 is mainly secreted by cancer associated fibroblast (CAFs), but not tumor cells in HCC. High IL-6 expression CAFs could induce strong immunosuppression in HCC microenvironment by recruiting immunosuppressive cells, such as myeloid derived suppressive cells. In addition, high IL-6 expression CAFs also impaired tumor infiltrating T-cell function via upregulating inhibitory immune checkpoints. Using IL-6 blockade could reverse anti-PD-L1 resistance in HCC tumor model. In conclusion, our study indicates that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in HCC, providing a potential strategy to overcoming anti-PD-L1 resistance in HCC. [ABSTRACT FROM AUTHOR]

As a multigene superfamily of Phase II detoxification enzymes, uridine diphosphate (UDP)-glycosyltransferases (UGTs) play important roles in the metabolism of xenobiotics including insecticides. In this study, 5-nitrouracil, an inhibitor of UGT enzyme activity, effectively increased the toxicity of chlorpyrifos to the chlorpyrifos-resistant strain of Nilaparvata lugens , one of the most resistant rice pests. The enzyme content of UGT in the resistant strain was significantly higher than that in the susceptible strain. Among 20 identified UGT genes, UGT386H2 , UGT386J2 , UGT386N2 and UGT386P1 were found significantly overexpressed in the resistant strain and can be effectively induced by chlorpyrifos. These four UGT genes were most highly expressed in the midgut and/or fat body, two main insect detoxification tissues. Amino acid sequence alignments revealed that these four UGTs contained a variable N-terminal substrate-binding domain and a conserved C-terminal sugar donor-binding domain. Furthermore, homology modeling and molecular docking analyses showed that these UGTs could stably bind to chlorpyrifos and chlorpyrifos oxon, with the binding free energies from −19.4 to −110.62 kcal mol−1. Knockdown of UGT386H2 or UGT386P1 by RNA interference dramatically increased the susceptibility of the resistant strain to chlorpyrifos. These findings suggest that overexpression of these two UGT genes contributes to chlorpyrifos resistance in N. lugens. [Display omitted] • Four UGTs were found to be overexpressed in chlorpyrifos-resistant N. lugens. • The overexpressed UGT genes were primarily expressed in midgut and/or fat body. • Chlorpyrifos could stably bind to these UGTs in molecular docking. • Overexpression of UGT386H2 and UGT386P1 was responsible for chlorpyrifos resistance. [ABSTRACT FROM AUTHOR]

Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear. In this study, we achieved simultaneous imaging of Ca2+ and temperature using the genetically encoded indicators, B-GECO and B-gTEMP. We then compared the spatiotemporal distributions of Ca2+ responses and temperature. Following neural excitation induced by veratridine, an activator of the voltage-gated Na+ channel, we observed an approximately 2 °C increase in cytosolic temperature occurring 30 s after the Ca2+ response. The temperature elevation was observed in the non-nuclear region, while Ca2+ increased throughout the cell body. Moreover, this temperature increase was suppressed under Ca2+-free conditions and by inhibitors of ATP synthesis. These results indicate that Ca2+-induced upregulation of energy metabolism serves as the heat source during neural excitation. • Simultaneous imaging of Ca2+ and temperature in neurons was achieved. • Veratridine-induced excitation of neurons heated the cytosol by approximately 2 °C. • The temperature increase was delayed by 30 s after the Ca2+ response. • Inhibition of ATP synthesis suppressed the temperature rise during neural excitation. [ABSTRACT FROM AUTHOR]

Abstract: Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell-specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4-overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners. [Copyright &y& Elsevier]

[Display omitted] • Fourteen new 2-benzylbenzofuran glycosides and one new key precursor, diarylacetone were isolated from the roots of Heterosmilax yunnanensis. • 2-Benzylbenzofuran O -glycosides were first found and all structures have characteristic 2, 3, 4- O -trisubstituted benzyl. • The cardioprotective activity of the 2-benzylbenzofuran skeleton was discovered for the first time. • Compounds 1 , 3 and 6 process a great cardiotonic function by eliminating ROS and restoring the ATP supplements. Fourteen new 2-benzylbenzofuran O -glycosides (1 – 13 , 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4- O -trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1 , 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1 , 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor 4 (HNF4) plays essential roles in regulating lipid metabolism and glucose homeostasis in female insects. However, little is known about the role of HNF4 in insect fecundity. Here we demonstrate that HNF4 regulates female fecundity by affecting egg hatching in the brown planthopper (BPH) Nilaparvata lugens. HNF4 was highly expressed in the ovary and fat body of female adult. RNA interference-mediated HNF4 knockdown resulted in a dramatic reduction in egg hatchability and caused a severe block in embryonic development, while showed no significant effects on ovary development and egg laying. Transcriptome sequencing analysis showed that 72 genes encoding ribosome proteins were significantly down-regulated in the HNF4 -silenced BPH and "ribosome" was the most-enriched pathway for the down-regulated genes. These results suggest that HNF4 controls the dynamics of egg structure, likely through its regulation of ribosome protein genes, which in turn affects the embryonic development and egg hatching. • HNF4 was highly expressed in the fat body and ovary of adult BPH female. • HNF4 knockdown resulted in a dramatic reduction in egg hatching rate. • Transcriptome sequencing analysis identified 3544 DEGs (1797 up-regulated and 1747 down-regulated) in the ovary of HNF4 -silenced BPH. • 72 ribosome genes were significantly down-regulated after HNF4 knockdown. • KEGG analysis showed that "ribosome" was the most-enriched pathway for the down-regulated genes. [ABSTRACT FROM AUTHOR]

Spodoptera litura , a polyphagous lepidopteran pest, demonstrates a remarkable capacity to adapt to varying host plants by efficiently detoxifying phytochemicals. However, the underlying mechanism for this adaptation is not well understood. Herein, twenty eplison glutathione S -transferase genes (GSTes) were characterized and their roles in phytochemical tolerance were analyzed in S. litura. Most of the GSTe genes were mainly expressed in the larval midgut and fat body. Exposure to the phytochemicals, especially xanthotoxin, induced the expression of most GSTe genes. Molecular docking analysis revealed that xanthotoxin could form stable bonds with six xanthotoxin-responsive GSTes, with binding free energies ranging from −36.44 to −68.83 kcal mol−1. Knockdown of these six GSTe genes increased the larval susceptibility to xanthotoxin. Furthermore, xanthotoxin exposure significantly upregulated the expression of two transcription factor genes CncC and MafK. Silencing of either CncC or MafK reduced the expression of GSTe16 , which exhibited the largest change in response to xanthotoxin. Additionally, analysis of the promoter sequence of GSTe16 revealed the presence of seven CncC/Maf binding sites. Luciferase reporter assays showed that CncC and MafK enhanced the expression of GSTe16 , leading to the increased xanthotoxin tolerance in S. litura. These findings provide insight into the functions and transcriptional regulatory mechanisms of GSTes, thereby enhancing our understanding of the role of GSTs in the adaptation of lepidopteran pests to phytochemicals. [Display omitted] • More than half of the GSTes were primarily expressed in larval midgut and fat body. • Six GSTes including GSTe16 were involved in xanthotoxin tolerance. • Xanthotoxin could stably bind to these six GSTes in molecular docking. • GSTe16 was transcriptionally regulated by CncC and MafK. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Neither Triplostegia glandulifera nor T. grandiflora is monophyletic. • Statistical analyses of morphological traits could not distinguish two species. • The integrative approach suggests treating Triplostegia as a monotypic genus. • Triplostegia may host four lineages currently undergoing allopatric speciation. • Analyses of chloroplast genomes provide insights into species delimitation. Abstract Species represent the most basic unit of taxonomy. As such, species delimitation represents a crucial issue for biodiversity conservation. Taxonomic practices were revolutionized in the last three decades due to the increasing availability of molecular phylogenetic data. The genus Triplostegia (Caprifoliaceae) traditionally consists of two species, T. glandulifera and T. grandiflora , distinguishable mainly based on quantitative morphological features. In this study, we sequenced nine chloroplast loci (i.e., accD , psbK - psbI , rbcL-accD , rpoB-trnC , rps16-trnQ , trnE-trnT , trnF-ndhJ , trnH-psbA , trnS-trnG) and one nuclear locus (ITS) of 16 individuals of Triplostegia representing the entire distribution range of both species recognized. Furthermore, we also obtained whole chloroplast sequences for 11 of the 16 individuals for which silica gel-dried leaves were available. Our phylogenetic analyses integrating chloroplast genome sequences and multiple loci data revealed that Triplostegia includes four main clades that largely match geography. Neither T. grandiflora nor T. glandulifera was recovered as monophyletic and no diagnosable differences in leaf, flower, and pollen traits were detected between the two species, indicating the need for a revised species circumscription within Triplostegia. Our study highlights the importance of combining data from different sources while defining species limits. [ABSTRACT FROM AUTHOR]

Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO 2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO 2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO 2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas. • Vehicles exhaust CO 2 and CO on elevated roads were 17.8% and 21.9% higher than those on ground roads. • The instantaneous CO 2 and CO emissions increase exponentially as VSP enhance. • CO 2 and CO concentrations on elevated road are 1.2% and 6.9% higher than that on ground road. [ABSTRACT FROM AUTHOR]

The Wnt/JNK pathway, responsible for tissue polarity in cardiogenesis in vertebrates, has been shown to play numerous roles during differentiation and development of cardiac myocytes. Van Gogh-like-2 (Vangl2) is a core component that regulates the induction of polarized cellular and tissue morphology during animal development. However, little is known about Wnt/JNK signaling pathway in the process of myocardial remodeling. In present study, we found that activation of Wnt/JNK signaling by Wnt5a stimulates enlargement of cardiomyocyte surface area. The hypertrophic features were inhibited in Vangl2 depleted cells. Meanwhile, Wnt/JNK activation induced cytoskeleton rearrangement but failed to activate these effects in cells lacking Vangl2. Moreover, Wnt/JNK activation significantly increased the cell apoptosis by mediating the mitochondrial permeability transition pore (mPTP) dysfunction, whereas knockdown of Vangl2 partly reversed these effects. These results suggest that activation of Wnt/JNK signaling stimulates myocardial remodeling (cell morphological changes, apoptosis and mitochondrial dysfunction), in which Vangl2 may play an essential role. [ABSTRACT FROM AUTHOR]

Phytochemicals are a class of potential pesticides for pest control. Our previous studies have demonstrated that the development of Spodoptera litura is suppressed by two phytochemicals, flavone and xanthotoxin. Generally, phytochemical is metabolized by insect detoxification enzyme systems. Nuclear receptor (NR) is the ligand-activated transcription factor that involved in the regulation of detoxification gene expressions. To explore how NR responds to phytochemical to mediate detoxification gene expression, in the present study, 19 NRs were firstly identified in S. litura genome. The transcriptional levels of most NRs were significantly induced in the midgut of S. litura larvae after exposure to flavone and xanthotoxin. RNAi-mediated knockdown of FTZ F1 , EcR , Dsf , and HR3 remarkably reduced the larval tolerance to flavone or xanthotoxin. In addition, many crucial detoxification genes were downregulated by dsNR administrations, which might be responsible for the high sensitivity of S. litura to phytochemicals. Molecular docking indicated that phytochemicals as the potential ligands had high affinity to bind to NRs. This study suggested that NR potentially regulated the transcriptional expression of detoxification genes in response to phytochemical stresses, which partially elucidated the mechanism of extensive host adaptation in S. litura and provided the theoretical evidences for the development of NR-targeted insecticides. [Display omitted] • Nineteen NRs were identified in S. litura genome. • NRs regulated S. litura larvae to detoxify phytochemicals. • NRs mediated the transcriptional levels of detoxification genes. • Phytochemicals were the potential ligands to combine with NRs. [ABSTRACT FROM AUTHOR]

The toxic effects of insecticides on predatory arthropods have closely related to their exposure routes. However, little is known about the effects of insecticide on reproductive parameters when the route of exposure occurs at a trophic level via prey intake. We therefore conducted current studies assessing whether Eocanthecona furcellata adults would be affected by feeding with λ -cyhalothrin-contaminated prey. Reproductive parameters, i.e. prolonged premating and preoviposition durations, reduced number of egg batches and egg amount, disturbed ovarian development, and suppressed expression of reproductive related genes were observed in E. furcellata females by feeding with treated prey. Moreover, reduced survival rate and altered carbohydrate metabolism parameters were detected in male bugs. Biochemical parameters, including MDA content, the activities of three antioxidant enzymes and three detoxification enzymes exhibited sex-specific responses after oral-exposure to λ -cyhalothrin in E. furcellata. The results indicate that the insecticide affects the fitness and leads to impairing reproductive potential via sex-specific modulation manner in predator insects. Taken together, our results provide a comprehensive assessment about detrimental impacts of λ -cyhalothrin-exposure on predators via prey intake, as well as a solid basis for further research to protect the predators from hazardous impacts of insecticides. [Display omitted] • Toxic effects were observed via oral-exposure to λ-cyhalothrin in E. furcellata. • Biochemical parameters of predator insects exhibited sex-differentially responses. • Insecticide impairs reproductive potential via sex-specific modulation manner. [ABSTRACT FROM AUTHOR]

Hepatopulmonary syndrome (HPS) is a complication of severe liver disease. It is characterized by an arterial oxygenation defect. Recent studies have demonstrated that pulmonary angiogenesis contributes to the abnormal gas exchange found in HPS. Additionally, mesenchymal stem cells (MSCs) are considered the stable source of VEGF-producing cells and have the potential to differentiate into multiple cell types. However, it has not been determined whether bone marrow mesenchymal stem cells (BM-MSCs) are mobilized and involved in the pulmonary angiogenesis in HPS. In this study, a CFU-F assay showed that the number of peripheral blood MSCs was increased in common bile duct ligation (CBDL) rats; however, there was no significant difference found in the number of BM-MSCs. In vitro, CBDL rat serum induced the overexpression of CXCR4 and PCNA in BM-MSCs. Consistently, the directional migration as well as the proliferation ability of BM-MSCs were enhanced by CBDL rat serum, as determined by a transwell migration and MTT assays. Moreover, the secretion of VEGF by BM-MSCs increased after treatment with CBDL rat serum. We also found that the expression of phospho-Akt, phospho-ERK, and Nrf2 in BM-MSCs was significantly up-regulated by CBDL rat serum in a time dependent manner, and the blockage of the Akt/Nrf2 signalling pathway with an Akt Inhibitor or Nrf2 siRNA, instead of an ERK inhibitor, attenuated the migration, proliferation and paracrine capacity of BM-MSCs. In conclusion, these findings indicated that the number of MSCs increased in the peripheral blood of CBDL rats, and the Akt/Nrf2 pathway plays a vital role in promoting the angiogenic related functions of BM-MSCs, which could be a potent contributor to pulmonary angiogenesis in HPS. [ABSTRACT FROM AUTHOR]

Highlights: [•] The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. [•] We found that the expression of miR-361-5p in CRPC was lower than in ADPC. [•] MiR-361-5p suppressed DU145 cell proliferation and triggered apoptosis. [•] STAT6 is a direct target of miR-361-5p. [•] STAT6 enhances the expression of Bcl-xL at the transcriptional level. [ABSTRACT FROM AUTHOR]

Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus–cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus–virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell–cell fusion was independent of cathepsin L, a protease essential for virus–cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus–cell and cell–cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation. [Copyright &y& Elsevier]

Abstract: Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24−ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC. [Copyright &y& Elsevier]

Abstract: CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133+) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133− cells. To evaluate the role of SirT1 in GBM-CD133+, we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133+. Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133+ to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in the inhibition of tumor growth in nude mice transplanted with GBM-CD133+. Kaplan–Meier survival analysis indicated that the mean survival rate of GBM-CD133+ mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy. [Copyright &y& Elsevier]

Preharvest sprouting (PHS) is one of the most serious defects that impacts rice production and grain quality. Knowledge about the effects of PHS on the eating and cooking quality (ECQ) of milled rice is limited. Here, we selected four japonica rice varieties to study the influences of PHS on grain quality. The results showed that PHS strongly led to poor grain appearance and the development of small starch granules whose surfaces were eroded. Analysis of starch fine structure revealed that PHS resulted in amylose (AM) degradation; in particular, PHS caused a decrease in the content of long AM chains. Moreover, PHS led to a decrease in the content of short amylopectin (AP) chains in the varieties Yandao 815 (YD815), Wuyugeng 27 (WY27) and Yangeng 13 (YG13), while the variety Sidao 785 (SD785) displayed the opposite trend. We propose that the main reasons for the decrease in starch crystallinity and the pasting profiles of the germinated rice were due to both the tendency of the AM content to decrease and the degree of this decrease in the content of the different AM chains along with changes in AP and other major components. All these changes caused by PHS led to a decrease in both ECQ and palatability of milled rice. Image 1 • Rice eating and cooking quality decreased after pre-harvest sprouting. • The physicochemical properties of rice kernels were greatly affected by pre-harvest sprouting. • Starch fine structures were deep causes of adverse effects of pre-harvest sprouting on grain quality. [ABSTRACT FROM AUTHOR]

While mothering is often instinctive and stereotyped in species-specific ways, evolution can favor genetically "open" behavior programs that allow experience to shape infant care. Among experience-dependent maternal behavioral mechanisms, sensory learning about infants has been hard to separate from motivational changes arising from sensitization with infants. We developed a paradigm in which sensory learning of an infant-associated cue improves a stereotypical maternal behavior in female mice. Mice instinctively employed a spatial memory-based strategy when engaged repetitively in a pup search and retrieval task. However, by playing a sound from a T-maze arm to signal where a pup will be delivered for retrieval, mice learned within 7 days and retained for at least 2 weeks the ability to use this specific cue to guide a more efficient search strategy. The motivation to retrieve pups also increased with learning on average, but their correlation did not explain performance at the trial level. Bilaterally silencing auditory cortical activity significantly impaired the utilization of new strategy without changing the motivation to retrieve pups. Finally, motherhood as compared to infant-care experience alone accelerated how quickly the new sensory-based strategy was acquired, suggesting a role for the maternal hormonal state. By rigorously establishing that newly formed sensory associations can improve the performance of a natural maternal behavior, this work facilitates future studies into the neurochemical and circuit mechanisms that mediate novel sensory learning in the maternal context, as well as more learning-based mechanisms of parental behavior in rodents. • Mice learn to switch from a spatial to a sound-based strategy to retrieve pups. • Sensory learning of pup-associated sounds is separable from maternal motivation. • Sound-specific learning lasts for more than 2 weeks. • Learned sound-based strategy requires auditory cortex. • Maternal state accelerates learning the sound-based strategy. [ABSTRACT FROM AUTHOR]

• An in-fiber Fabry-Perot interferometer (FPI) sensor based on SMF-HCF-GPCF configuration is proposed. • The dip intensity has a RH sensitivity of 0.06273 dB/%RH in the range of 35–71%RH. • The dip wavelength has a temperature sensitivity of 10.64 pm/°C in the range of 25–70 °C. In this work, an in-fiber Fabry-Perot interferometer (FPI) is proposed and experimentally demonstrated for ambient relative humidity (RH) and temperature measurements. The FPI is manufactured from short segments of hollow-core fiber (HCF) and photonic crystal fiber (PCF). The air-cavity in the HCF segment enables a strong light-air interaction whereas the air holes of the PCF serve as vents which enable the exchange of air between the air-cavity and the surrounding medium. Our findings show that the dip intensity is solely sensitive to the change in RH with a linear sensitivity of 0.06273 dB/%RH in the range of 35–71%RH whereas the dip wavelength is solely sensitive to the ambient temperature with a linear sensitivity of 10.64 pm/°C in the range of 25–70 °C. The cross-sensitivity between the two measurands can be disregarded, therefore no sophisticated equation is required for the discriminative measurement of humidity and temperature. [ABSTRACT FROM AUTHOR]