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Guosheng Cao, Xinyi Ye, Yingqiong Xu, Mingzhu Yin, Honglin Chen, Junping Kou, Boyang Yu Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB) dysfunction induced by cerebral ischemia–reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. Keywords: YiQiFuMai powder injection, YQFM, ischemic stroke, blood–brain barrier, microvascular permeability, tight junctions

Intraspinal cold abscesses caused by macrolide-resistant Mycoplasma pneumoniae in patients with X-linked agammaglobulinemia have not yet been described to our knowledge. Here we describe a patient with X-linked agammaglobulinemia who developed an intraspinal cold abscess caused by macrolide-resistant M. pneumoniae . Genetic analysis revealed a hemizygous c.1566 + 1G > C (IVS15 + 1G > C) mutation in BTK gene. The patient showed relatively naive T cells and a significant proliferative defect., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD., Methods: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe 2+ ) and trivalent iron (Fe 3+ ) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress., Results: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe 2+ , MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway., Conclusion: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; 22(4): 494-503., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206 , a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Value hierarchies, as motivational goals anchored in the self-schema, may be correlated with spontaneous activity in the resting brain, especially those involving self-relevance. This study aims to investigate the neural correlates of value hierarchies from the perspective of typology., Methods: A total of 610 Chinese college students (30.31% women), aged 18 to 23, completed the personal values questionnaire and underwent resting-state functional magnetic resonance imaging., Results: The latent profile analysis revealed three personal value profiles: traditional social orientation, modernized orientation, and undifferentiated orientation. Neuroimaging results revealed that individuals with modernized orientation prioritized openness to change value, and this personal-focus is related to the higher low-frequency amplitude of the posterior insula; individuals with traditional social orientation prioritized self-transcendence and conservation values, and this social-focus is related to the stronger functional connectivity of the middle insula with the inferior temporal gyrus, temporal gyrus, posterior occipital cortex, and basal ganglia, as well as weaker functional connections within the right middle insula., Discussion: Taken together, these findings potentially indicate the intra-generational differentiation of contemporary Chinese emerging adults' value hierarchies. At the neural level, these are correlated with brain activities involved in processing self- and other-relevance., 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. The reviewer TB declared a past co-authorship with the author JQ to the handling editor., (Copyright © 2023 Xie, Tian, Hu, Yin, Sun, Shan, Chen, Feng and Qiu.)

Spatial transcriptomics technologies enable researchers to accurately quantify and localize messenger ribonucleic acid (mRNA) transcripts at a high resolution while preserving their spatial context. The identification of spatial domains, or the task of spatial clustering, plays a crucial role in investigating data on spatial transcriptomes. One promising approach for classifying spatial domains involves the use of graph neural networks (GNNs) by leveraging gene expressions, spatial locations, and histological images. This study provided a comprehensive overview of the most recent GNN-based methods of spatial clustering methods for the analysis of data on spatial transcriptomics. We extensively evaluated the performance of current methods on prevalent datasets of spatial transcriptomics by considering their accuracy of clustering, robustness, data stabilization, relevant requirements, computational efficiency, and memory use. To this end, we explored 60 clustering scenarios by extending the essential frameworks of spatial clustering for the selection of the GNNs, algorithms of downstream clustering, principal component analysis (PCA)-based reduction, and refined methods of correction. We comparatively analyzed the performance of the methods in terms of spatial clustering to identify their limitations and outline future directions of research in the field. Our survey yielded novel insights, and provided motivation for further investigating spatial transcriptomics., Competing Interests: All of the authors have no conflicts of interest to declare., (© 2023 The Authors.)

Chemosensory proteins (CSPs) are involved in the earliest steps of the olfactory process by binding and transporting odorants and play a crucial role in the insect's search for food and egg-laying sites. In the present study, the tissue expression profiles showed that both CchiCSP3 and CchiCSP5 of Callosobruchus chinensis were highly expressed in the adult antennae. Subsequently, the recombinant CchiCSP3 and CchiCSP5 proteins were analysed using fluorescence competitive binding assays, and both showed binding affinities for the three mung bean volatiles. Molecular docking and site-directed mutagenesis revealed four key amino acid residues in CchiCSP3 (L47, W80, Y81, and L84) and CchiCSP5 (Y28, K46, L49, and I72). Electroantennogram (EAG) and dual-choice biobehavioral assays showed that the antennae of adult C. chinensis were electrophysiologically active in response to stimulation with all three behaviorally active compounds and that octyl 4-methoxycinnamate and β-ionone had a significant luring effect on adult C. chinensis, whereas vanillin had a significant avoidance effect. Our study screened three effective behaviorally active compounds based on the involvement of two CchiCSPs in the recognition of mung bean volatiles, providing an opportunity to develop an alternative control strategy using behavioral disruptors to limit the impact of pests., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females., Methods: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500)., Findings: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses., Interpretation: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Riptortus pedestris (bean bug), a common soybean pest, has a highly developed olfactory system to find hosts for feeding and oviposition. Chemosensory proteins (CSPs) have been identified in many insect species; however, their functions in R. pedestris remain unknown. In this study, quantitative real time-polymerase chain reaction (qRT-PCR) revealed that the expression of RpedCSP12 in the adult antennae of R. pedestris increased with age. Moreover, a significant difference in the expression levels of RpedCSP12 was observed between male and female antennae at one and three days of age. We also investigated the binding ability of RpedCSP12 to different ligands using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP12 only bound to one aggregation pheromone, (E)-2-hexenyl (Z)-3-hexenoate, and its binding decreased with increasing pH. Furthermore, homology modelling, molecular docking, and site-directed mutagenesis revealed that the Y27A, L74A, and L85A mutants lost their binding ability to (E)-2-hexenyl (Z)-3-hexenoate. Our findings highlight the olfactory roles of RpedCSP12, providing insights into the mechanism by which RpedCSPs bind to aggregation pheromones. Therefore, our study can be used as a theoretical basis for the population control of R. pedestris in the future., (Copyright © 2023. Published by Elsevier Inc.)

Background: α-Mangostin is a xanthone isolated from the pericarps of mangosteen fruit with, and has analgesic properties. Although the effects suggest an interaction of α-mangostin with ion channels in the nociceptive neurons, electrophysiological investigation of the underlying mechanism has not been performed., Hypothesis: We hypothesized that α-Mangostin exerts its analgesic effects by modulating the activity of various ion channels in dorsal root ganglion (DRG) neurons., Methods: We performed a whole-cell patch clamp study using mouse DRG neurons, HEK293T cells overexpressing targeted ion channels, and ND7/23 cells. Molecular docking (MD) and in silico absorption, distribution, metabolism, and excretion (ADME) analyses were conducted to obtain further insights into the binding sites and pharmacokinetics, respectively., Results: Application of α-mangostin (1-3 µM) hyperpolarized the resting membrane potential (RMP) of small-sized DRG neurons by increasing background K + conductance and thereby inhibited action potential generation. At micromolar levels, α-mangostin activates TREK-1, TREK-2, or TRAAK, members of the two-pore domain K + channel (K2P) family known to be involved in RMP formation in DRG neurons. Furthermore, capsaicin-induced TRPV1 currents were potently inhibited by α-mangostin (0.43 ± 0.27 µM), and partly suppressed tetrodotoxin-sensitive voltage-gated Na + channel (Na V ) currents. MD simulation revealed that multiple oxygen atoms in α-mangostin may form stable hydrogen bonds with TREKs, TRAAK, TRPV1, and Na V channels. In silico ADME tests suggested that α-mangostin may satisfy the drug-likeness properties without penetrating the blood-brain barrier., Conclusion: The analgesic properties of α-mangostin might be mediated by the multi-target modulation of ion channels, including TREK/TRAAK activation, TRPV1 inhibition, and reduction of the tetrodotoxin-sensitive Na V current. The findings suggest that the phytochemical can be a multi-ion channel-targeting drug and an alternative drug for effective pain management., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Nano-delivery systems have been applied to deliver various synthetic/botanical pesticides to increase the efficiency of pesticide use and reduce the volumes of pesticides applied. Previous studies have supported the hypothesis that the nanocarriers can help expand the insecticidal target of pesticides to include non-target pests. However, the potential mechanism underlying this interesting phenomenon remains unclear. Herein, a widely applied star polycation (SPc) nanocarrier was synthesized to construct a thiamethoxam (TMX) nano-delivery system. The SPc-based delivery system could promote the translocation of exogenous substances across the membrane of Sf9 cells, increase the cytotoxicity of TMX against Sf9 cells by nearly 20%, and expand the insecticidal target of TMX to include Spodoptera frugiperda (the fall armyworm), with a 27.5% mortality increase at a concentration of 0.25 mg/mL. Moreover, the RNA-seq analysis demonstrated that the SPc could upregulate various transport-related genes, such as Rab, SORT1, CYTH, and PIKfyve, for the enhanced cellular uptake of TMX. Furthermore, enhanced cell death in larvae treated with the TMX-SPc complex was observed through changes in the expression levels of death-related genes, such as Casp7, BIRC5, MSK1, and PGAM5. The SPc-based nano-delivery system improved the cellular uptake of TMX and expanded its insecticidal target by adjusting the expression levels of death-related genes. The current study mainly identified the transport and cell death genes related to nanocarrier-based insecticidal target expansion, which is beneficial for understanding the bioactivity enhancement of the nano-delivery system., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

Advancing spatially resolved transcriptomics (ST) technologies help biologists comprehensively understand organ function and tissue microenvironment. Accurate spatial domain identification is the foundation for delineating genome heterogeneity and cellular interaction. Motivated by this perspective, a graph deep learning (GDL) based spatial clustering approach is constructed in this paper. First, the deep graph infomax module embedded with residual gated graph convolutional neural network is leveraged to address the gene expression profiles and spatial positions in ST. Then, the Bayesian Gaussian mixture model is applied to handle the latent embeddings to generate spatial domains. Designed experiments certify that the presented method is superior to other state-of-the-art GDL-enabled techniques on multiple ST datasets. The codes and dataset used in this manuscript are summarized at https://github.com/narutoten520/SCGDL., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Callosobruchus chinensis (Coleoptera: Fabaceae) is a worldwide pest that feeds exclusively on legumes, and is the most serious pest affecting mung beans. Usually, the insect olfactory system plays a predominant role in searching for host plants and egg-laying locations. Chemosensory proteins (CSPs), are mainly responsible for transporting specific odour molecules from the environment. In this study, we found that the CSP1 gene of adult C. chinensis displayed antennae-biased expression using quantitative real-time PCR (qRT-PCR) analysis. The binding properties of 23 mung bean volatiles were then determined through several analyses of in vitro recombinant CSP1 protein, including fluorescence competitive binding assay, homology modelling, molecular docking, and site-directed mutagenesis. Fluorescence competitive binding assays showed that CchiCSP1 protein could bind to four mung bean volatiles and was most stable at pH 7.4. After site-directed mutation of three key amino acid bases (L39, V25, and Y35), their binding affinities to each ligand were significantly decreased or lost. This indicated that these three amino acid residues may be involved in the binding of CchiCSP1 to different ligands. We further used Y-tube behavioural bioassays to find that the four mung bean volatiles had a significant attraction or repulsion response in adult C. chinensis. The above findings confirm that the CchiCSP1 protein may be involved in the response of C. chinensis to mung bean volatiles and plays an important role in olfactory-related behaviours. The four active volatiles are expected to develop into new behavioural attractants or repellents in the future., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A precise chemosensory system can help insects complete various important behavioral responses by accurately identifying different external odorants. Therefore, deeply understanding the mechanism of insect recognition of important odorants will help us develop efficient and environmentally-friendly behavioral inhibitors. Spodoptera frugiperda is a polyphagous pest that feeds on >350 different host plants worldwide and also harms maize production in China. However, the molecular mechanism of the first step for males to use odorant-binding proteins (OBPs) to recognize sex pheromones remains unclear. Here, we obtained 50 OBPs from the S. frugiperda genome, and the expression level of SfruGOBP1 in females was significantly higher than that in males, whereas SfruGOBP2 displayed male-biased expression. Fluorescence competitive binding assays showed that only SfruGOBP2 showed binding affinities for the four sex pheromones of female S. frugiperda. Subsequently, we identified some key amino acid residues that can participate in the interaction between SfruGOBP2 and sex pheromones using molecular docking and site-directed mutagenesis methods. These findings will help us explore the interaction mechanism between GOBPs and sex pheromones in moths, and provide important target genes for developing new mating inhibitors of S. frugiperda in the future., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Adiponectin (APN) is a kind of endogenous anti-tumor adipocytokine, which exerts its function by binding to its receptors (AdipoR1 and AdipoR2). However, hyperadiponectinemia is found in some pathophysiological processes without significant protective effect, which indicates the existence of APN resistance. Here, we aimed to investigate the locoregional expression of APN in tongue squamous cell carcinoma (TSCC) tissues, and to explore the potential regulatory mechanism of APN resistance under hypoxia. Consequently, we found that the protein expression of APN and AdipoR1, but not AdipoR2, was upregulated in the early stage of TSCC and after hypoxic treatment ex vivo and in vitro. Knockdown of HIF-1α decreased the level of APN and AdipoR1, and simultaneously, HIF-1α was identified as transcriptor of the APN. Intriguingly, a regenerative feedback of HIF-1α was unexpectedly detected after application of recombinant globular APN (gAPN), which most likely contributed to the APN resistance. Furthermore, HIF-1α blockade combined with gAPN has a prominent synergistic antitumor effect, which suggested an effective amelioration in APN resistance. In all, our study revealed the possible mechanism of APN resistance under hypoxia and provides a promising strategy of bi-target treatment with APN and HIF-1α for TSCC therapy., (© 2021 Wiley Periodicals LLC.)

The unscientific application of synthetic pesticides has brought various negative effects on the environment, hindering the sustainable development of agriculture. Nanoparticles can be applied as carriers to improve pesticide delivery, showing great potential in the development of pesticide formulation in recent years. Herein, a star polymer (SPc) was constructed as an efficient pesticide nanocarrier/adjuvant that could spontaneously assemble with thiocyclam or monosultap into a complex, through hydrophobic association and hydrogen bonding, respectively, with the pesticide-loading contents of 42.54% and 19.3%. This complexation reduced the particle sizes of thiocyclam from 543.54 to 52.74 nm for pure thiocyclam, and 3 814.16 to 1 185.89 nm for commercial preparation (cp) of thiocyclam. Interestingly, the introduction of SPc decreased the contact angles of both pure and cp thiocyclam on plant leaves, and increased the plant uptake of cp thiocyclam to 2.4-1.9 times of that without SPc. Meanwhile, the SPc could promote the bioactivity of pure/cp thiocyclam against green peach aphids through leaf dipping method and root application. For leaf dipping method, the 50% lethal concentration decreased from 0.532 to 0.221 g/L after the complexation of pure thiocyclam with SPc, and that decreased from 0.390 to 0.251 g/L for cp thiocyclam. SPc seems a promising adjuvant for nanometerization of both pure and cp insecticides, which is beneficial for improving the delivery efficiency and utilization rate of pesticides., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

The bean bug Riptortus pedestris is a notorious insect pest that can damage various crops, especially soybean, in East Asia. In insects, the olfactory system plays a crucial role in host finding and feeding behaviour in which the odorant-binding proteins (OBPs) are believed to be involved in initial step in this system. In this study, we produced the R. pedestris adult antennae-expressed RpedOBP4 protein using a recombinant expression system in E. coli. Fluorescence competitive binding confirmed that RpedOBP4 has binding affinities to 7 of 20 soybean volatiles (ligands), and that a neutral condition is the best environment for it. The binding property of RpedOBP4 to these ligands was further revealed by integrating data from molecular docking, site-directed mutagenesis and ligand binding assays. This demonstrated that five amino acid residues (I30, L33, Y47, I57 and Y121) are involved in the binding process of RpedOBP4 to corresponding ligands. These findings will not only help us to more thoroughly explore the olfactory mechanism of R. pedestris during feeding on soybean, but also lead to the identification of key candidate targets for developing environmental and efficient behaviour inhibitors to prevent population expansion of R. pedestris in the future., (© 2022 Royal Entomological Society.)

Usually, the recognition of sex pheromone signals is restricted to adult moths. Here, our behavioral assay showed that fourth-instar Spodoptera litura larvae are attracted to cabbage laced with minor sex pheromones Z9,E12-tetradecadienyl acetate (Z9,E12-14:Ac) or Z9-tetradecenyl acetate (Z9-14:Ac). Seven odorant-binding proteins (OBPs) were upregulated after exposure to Z9,E12-14:Ac, and one OBP was upregulated after exposure to Z9-14:Ac. Fluorescence competitive binding assays showed that GOBP2 and OBP7 bound to sex pheromones. RNAi treatment significantly downregulated GOBP2 and OBP7 mRNA expression by 70.37 and 63.27%, respectively. The siOBP-treated larvae were not attracted to Z9,E12-14:Ac or Z9-14:Ac, and the corresponding preference indices were significantly lower than those in siGFP-treated larvae. Therefore, we concluded that GOBP2 and OBP7 are involved in the attraction of S. litura larvae to food containing Z9,E12-14:Ac and Z9-14:Ac. These results provide an important basis for exploring the olfactory mechanisms underlying sex pheromone attraction in moth larvae.

Ben Cao Tu Jing had 48 materia medica illustrations related to the regional names in Shandong province. It was found that 42 of them were plant medicinal materials, distributed in seven areas in Shandong province. This study examined these illustration of plant medicinal materials and found that 26 species of these illustration of plant medicinal materials were identified with three genera and 11 illustrations were unverified. Most materia medica illustrations relating to the regional names in Shandong province were found mainly in Yanzhou, Qizhou and Zizhou. This indicated that materia medica were widely used in these areas in the Northern Song Dynasty. The haustorium of Cuscuta Chinensis were depicted in the "Shanzhou Tu Si Zi" and the habitat of wild poriacocos was described. This showed that the illustrators of Ben Cao Tu Jing might have conducted fieldwork and reflected on the main principles about how to identify materia medica in Ben Cao Tu Jing Zou Chi . Inconsistencies were found between the illustrations and the expressions of plant medicinal materials in some illustrations, such as Gui Jiu, Ginsen and Shan Zhu Yu. This suggested that in the Northern Song Dynasty Stemmacantha Uniflora, Belamcanda chinensis might have been mixed up with Dysosma and Pinellia Pedatisecta might have been mixed up with Pinellia Ternata. This was in line with the compiling theories of Su Song that they could be recorded together when the illustrations and literature were inconsistent with each other.

Despite considerable disruption of social order caused by the COVID-19 pandemic, it has also been said to contribute to positive psychological changes and influence on the perception of public life satisfaction. The present study aimed to explore the association between the COVID-19 related posttraumatic growth and life satisfaction and the mediating role of personal values. A two-wave longitudinal design was used. 226 self-quarantined Chinese college students (58.8% male) completed post traumatic growth inventory (Time 1), satisfaction with life scale (Time 2), personal values questionnaire (Time 2) between February 2020 and May 2021. Results showed that more than half of self-quarantined Chinese college students reported moderate to high levels of the COVID-19 related posttraumatic growth. A structural equation model revealed that COVID-19 related posttraumatic growth was positively associated to life satisfaction, and self-transcendence and self-enhancement values partially mediated this association. These findings shed light on whether and how pandemic-related posttraumatic growth influenced personal life satisfaction, supporting the outcome and process perspectives of posttraumatic growth as well as Schwartz's value theory. Based on the findings, some positive psychology interventions, such as online rumination activities and mindfulness practice, were proposed to enhance self-quarantined college students' posttraumatic growth and life satisfaction., 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 Xie, Zhang, Zhang, Yin, Yang, Chen, Xiong and Chen.)

Insects have sensitive olfactory systems to interact with environment and respond to the change in host plant conditions. Key genes in the system can be potential targets for developing new and efficient pest behaviour control methods. Riptortus pedestris is an important soybean pest in East Asia and has caused serious damage to the soybean plants in Huang-Huai-Hai region of China. However, the current treatment of pests is dominated by chemical insecticides and lacks efficient sustainable prevention and control technologies. In this study, we identified 49 putative odorant-binding proteins (OBPs) (43 were new genes) and 25 chemosensory proteins (CSPs) (17 were new genes) in R. pedestris genome. These OBP and CSP genes are clustered in highly conserved groups from other hemipteran species in phylogenetic trees. Most RpedOBPs displayed antennal-biased expression. Among the 49 RpedOBPs , 33 were significantly highly expressed in the antennae, including three male-biased and nine female-biased. While many RpedCSPs were detected both in the antennae and in non-antennal tissues, only 11 RpedCSPs displayed antennal-biased expression, in which four RpedCSPs were male-biased and five RpedCSPs were female-biased. Some OBP and CSP genes showed sex-biased expression profiles. Our results not only provide a foundation for future exploration of the functions of RpedOBPs and RpedCSPs but also aid in developing environmentally friendly insecticides in the future., 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 Li, Yin, Yao, Ma, Dewer, Liu, Wang, Wang, Li and Zhu.)

Ben Cao Tu Jing had 38 materia medica illustrations related to the regional names in Zhejiang province. It was found that 30 of them were identified as being named after regional names in Zhejiang province, involving 20 families and 29 genera. One of the 38 materia medica illustrations was mineral medicine and seven of them were unverified. The twenty-five of these materia medica illustrations with regional names were found to be consistent with their names used today. Five of them came from similar names in Zhejiang province in the Northern Song Dynasty, another five of the 25 names were known with the names but not entity for the lack of full descriptions and drawings. It was found that the drawing and the text of "Ming Zhou Huang Yao" and "Qin Zhou Hong Yao" in Ben Cao Tu Jing were reversed. By comparing the materia medica illustrations related to regional names in Da Guan Ben Cao by Liu Jia and Zheng He Ben Cao by Zhang Huicun, the name and the illustration of "Jin Zhou Bei Mu" in Zheng He Ben Cao by Zhang Huicun was more believable than "Yue Zhou Bei Mu" in Da Guan Ben Cao by Liu Jia. "Tai Zhou Wu Yao" and "Zhe Ba Wei", as genuine medicinal materials in Zhejiang, can be traced back to the illustrations of "Tai Zhou Wu Yao", "Yue Zhou Bai Zhu", "Mu Zhou Mai Dong", "Wen Zhou Peng 'e Shu", "Yue Zhou Bei Mu" and "Tian Tai Wu Yao" in Ben Cao Tu Jing. These findings provided text and drawing literature of herbs in the Song Dynasty for the research of genuine medicinal materials and their characteristics in Zhejiang province. They also showed that the utilization and development of the resources of traditional Chinese medicine in Zhejiang in the Northern Song Dynasty mainly focused on the coastal areas.

Background: Reactive oxygen species (ROS) and calcium ions (Ca 2+ ) are among the major effectors of Ang II (angiotensin II) in vascular smooth muscle cells. ROS are related to Ca 2+ signaling or contraction induced by Ang II, but little is known about their detailed functions. Here, NOX (NADPH oxidase), a major ROS source responsive to Ang II, was investigated regarding its contribution to Ca 2+ signaling., Methods: Vascular smooth muscle cells were primary cultured from rat aorta. Ca 2+ and ROS were monitored mainly using fura-2 and HyPer family probes' respectively. Signals activating NOX were examined with relevant pharmacological inhibitors and genetic manipulation techniques., Results: Ang II-induced ROS generation was found to be biphasic: the first phase of ROS production, which was mainly mediated by NOX1, was small and transient, preceding a rise in Ca 2+ , and the second phase of ROS generation, mediated by NOX1 and NOX4, was slow but sizeable, continuing over tens of minutes. NOX1-derived superoxide in the first phase is required for Ca 2+ influx through nonselective cation channels. AT1R (Ang II type 1 receptor)-G βγ -PI3K γ (phosphoinositide 3-kinase γ) signaling pathway was responsible for the rapid activation of NOX1 in the first phase, while in the second phase, NOX1 was further activated by a separate AT1R-Gα q/11 -PLC (phospholipase C)-PKC β (protein kinase C β) signaling axis. Consistent with these observations, aortas from NOX1-knockout mice exhibited reduced contractility in response to Ang II, and thus the acute pressor response to Ang II was also attenuated in NOX1-knockout mice., Conclusions: NOX1 mediates Ca 2+ signal generation and thereby contributes to vascular contraction and blood pressure elevation by Ang II.

A total of 568 paintings of herbaceous plants and woody plants as medicine were involved in Ben Cao Tu Jing , accounting for 60% of the total drug illustrations and 76% of the botanical medicine paintings. These medicinal paintings can be classified into four types: original plant paintings, medicinal material paintings, plant and medicinal material paintings, and plant and their habitat paintings. The original plant paintings can be specifically divided into five sections: the whole plant paintings with roots, partial aerial part paintings with roots, plant paintings with ground lines, rootless plant paintings, and broken branch paintings. Among them, the drawings of " the broken branch paintings " and " the whole plant paintings with roots " are consistent with the basic principles of collecting plant specimens. Additionally, "the plant and medicinal material paintings " and "the medicinal material paintings "reflect that they were drawn based on the market survey of medicinal materials or collected medicinal materials specimens. These medicine painting demonstrate rich characteristics of medicinal plants and medicinal materials and a high artistic quality with realistic details.These paintings in Ben Cao Tu Jing echoes Tu Jing , combine the art of painting with the cognition ofnatural science, as the rudiment of early paintings of plant science.

Matched molecular pairs analysis (MMPA) has become a powerful tool for automatically and systematically identifying medicinal chemistry transformations from compound/property datasets. However, accurate determination of matched molecular pair (MMP) transformations largely depend on the size and quality of existing experimental data. Lack of high-quality experimental data heavily hampers the extraction of more effective medicinal chemistry knowledge. Here, we developed a new strategy called quantitative structure-activity relationship (QSAR)-assisted-MMPA to expand the number of chemical transformations and took the logD7.4 property endpoint as an example to demonstrate the reliability of the new method. A reliable logD7.4 consensus prediction model was firstly established, and its applicability domain was strictly assessed. By applying the reliable logD7.4 prediction model to screen two chemical databases, we obtained more high-quality logD7.4 data by defining a strict applicability domain threshold. Then, MMPA was performed on the predicted data and experimental data to derive more chemical rules. To validate the reliability of the chemical rules, we compared the magnitude and directionality of the property changes of the predicted rules with those of the measured rules. Then, we compared the novel chemical rules generated by our proposed approach with the published chemical rules, and found that the magnitude and directionality of the property changes were consistent, indicating that the proposed QSAR-assisted-MMPA approach has the potential to enrich the collection of rule types or even identify completely novel rules. Finally, we found that the number of the MMP rules derived from the experimental data could be amplified by the predicted data, which is helpful for us to analyze the medicinal chemical rules in local chemical environment. In summary, the proposed QSAR-assisted-MMPA approach could be regarded as a very promising strategy to expand the chemical transformation space for lead optimization, especially when no enough experimental data can support MMPA., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Substructure screening is widely applied to evaluate the molecular potency and ADMET properties of compounds in drug discovery pipelines, and it can also be used to interpret QSAR models for the design of new compounds with desirable physicochemical and biological properties. With the continuous accumulation of more experimental data, data-driven computational systems which can derive representative substructures from large chemical libraries attract more attention. Therefore, the development of an integrated and convenient tool to generate and implement representative substructures is urgently needed., Results: In this study, PySmash, a user-friendly and powerful tool to generate different types of representative substructures, was developed. The current version of PySmash provides both a Python package and an individual executable program, which achieves ease of operation and pipeline integration. Three types of substructure generation algorithms, including circular, path-based and functional group-based algorithms, are provided. Users can conveniently customize their own requirements for substructure size, accuracy and coverage, statistical significance and parallel computation during execution. Besides, PySmash provides the function for external data screening., Conclusion: PySmash, a user-friendly and integrated tool for the automatic generation and implementation of representative substructures, is presented. Three screening examples, including toxicophore derivation, privileged motif detection and the integration of substructures with machine learning (ML) models, are provided to illustrate the utility of PySmash in safety profile evaluation, therapeutic activity exploration and molecular optimization, respectively. Its executable program and Python package are available at https://github.com/kotori-y/pySmash., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

4-Oxo-nonenal (4-ONE) is an endogenous lipid peroxidation product that is more reactive than 4-hydroxy-nonenal (4-HNE). We previously reported the arrhythmic potential of 4-HNE by suppression of cardiac human Ether-a-go-go Related Gene (hERG) K + channels with prolonged action potential duration (APD) in cardiomyocytes. Here, we illustrate the higher arrhythmic risk of 4-ONE by modulating the cardiac hNa V 1.5 channel currents (I NaV ). Although the peak amplitude of I NaV was not significantly changed by 4-ONE up to 10 μM, the rate of I NaV inactivation was slowed, and the late Na + current (I NaL ) became larger by 10 μM 4-ONE. The chemical modification of specific residues in hNa V 1.5 by 4-ONE was identified using MS-fingerprinting analysis. In addition to the changes in I NaV , 4-ONE decreased the delayed rectifier K + channel currents including the hERG current. The L-type Ca 2+ channel current was decreased, whereas its inactivation was slowed by 4-ONE. The APD prolongation by 10 μM of 4-ONE was more prominent than that by 100 μM of 4-HNE. In the computational in silico cardiomyocyte simulation analysis, the changes of I NaL by 4-ONE significantly exacerbated the risk of arrhythmia exhibited by the TdP marker, qNet. Our study suggests an arrhythmogenic effect of 4-ONE on cardiac ion channels, especially hNa V 1.5.

Background: The utilization efficiency of conventional insecticides is comparatively low in agricultural production, which leads to their excessive application and environmental pollution. Insecticide nanometerization by polymers and polymeric materials has advantages, particularly increased utilization efficiency and reduced insecticide application., Results: To increase the utilization efficiency of insecticides, a star polycation (SPc) was selected as a drug carrier that could be complexed with thiamethoxam through electrostatic interaction. Formation of the complex decreased the particle size of thiamethoxam from 575.77 to 116.16 nm in aqueous solution. Plant uptake of SPc-delivered thiamethoxam was increased 1.69-1.84 times compared with thiamethoxam alone. Nano-sized thiamethoxam/SPc complexes showed enhanced contact and stomach toxicity against green peach aphids., Conclusion: SPc is a promising insecticide adjuvant for insecticide nanometerization, and is beneficial in improving insecticidal activity and decreasing the application amounts and application rates of conventional insecticides. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment. Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR. Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1β in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells. Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs., 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 © 2021 Lu, Xiao, Yin, Zhou, Wu, Chen, Luo, Kuang and Zhu.)

Polygonatum cyrtonema is a famous bulk medicinal material which is the medicinal and edible homologous. With the implementation of the traditional Chinese medicine industry to promote precise poverty alleviation, the planting area of P. cyrtonema in Jinzhai is becoming larger and larger in recent years. Jinzhai is located in the Dabie Mountainous area, which is the largest mountain area and county in Anhui Province. The cultivation of P. cyrtonema is scattered, and the traditional Chinese medicine resources investigation is not only inefficient and accurate. In this study,the "Resource 3"(ZY-3) remote sensing image was used as the best observation phase,and the method of support vector machine classification was used. The method of parallelepiped, minimum distance, mahalanob is distance, maximum likelihood classification and neural net were used to classify and recognize the P. cyrtonema in the whole region. In order to determine the accuracy and reliability of classification results, the accuracy of six supervised classification results was evaluated by confusion matrix method, and the advantages and disadvantages of six supervised classification methods for extracting P. cyrtonema field planting area were compared and analyzed. The results showed that the method of support vector machine classification was more appropriate than that using other classification methods. It provides a scientific basis for monitoring the planting area of P. cyrtonemain field.

With the spread of the novel coronavirus disease 2019 (COVID-19) around the world, the estimation of the incubation period of COVID-19 has become a hot issue. Based on the doubly interval-censored data model, we assume that the incubation period follows lognormal and Gamma distribution, and estimate the parameters of the incubation period of COVID-19 by adopting the maximum likelihood estimation, expectation maximization algorithm and a newly proposed algorithm (expectation mostly conditional maximization algorithm, referred as ECIMM). The main innovation of this paper lies in two aspects: Firstly, we regard the sample data of the incubation period as the doubly interval-censored data without unnecessary data simplification to improve the accuracy and credibility of the results; secondly, our new ECIMM algorithm enjoys better convergence and universality compared with others. With the framework of this paper, we conclude that 14-day quarantine period can largely interrupt the transmission of COVID-19, however, people who need specially monitoring should be isolated for about 20 days for the sake of safety. The results provide some suggestions for the prevention and control of COVID-19. The newly proposed ECIMM algorithm can also be used to deal with the doubly interval-censored data model appearing in various fields., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Dabie Mountain in Anhui province is a genuine producing area of Poria cocos, commonly known as Anling. Jinzhai county in Anhui province is a traditional producing area of P. cocos, and it is also a key county for poverty alleviation in Dabie Mountains. Poverty alleviation of traditional Chinese medicine producing area is an important measure to implement the major strategic deployment of the central government. The planting of P. cocos is helpful to promote the development of traditional Chinese medicine industry in Dabie Mountains and help poverty alleviation. P. cocos is a saprophytic fungus with special demands on soil and ecological environment, and its planting appears a scattered and irregular distribution. Traditional investigation methods are time-consuming and laborious, and the results are greatly influenced by subjective factors. In order to obtain the suitable planting area of P. cocos in Jinzhai county, according to the field survey, the research team has explored the regional, biological characteristics and cultivation methods of P. cocos in the county, and obtained the altitude distribution area suitable for the growth of P. cocos. Then, the MaxEnt niche model was used to analyze the relationship between ecological factors and distribution areas, and the potential distribution zoning of P. cocos in Jinzhai county was studied. Combined with the characteristics of P. cocos planting pattern, taking ZY-3 remote sensing image as the data source, the maximum likelihood method was used to extract the area that could be used for P. cocos cultivation in Jinzhai county, and the reason why artificial planting P. cocos was mainly distributed in the west of Jinzhai county was analyzed. The suitable regional classification of P. cocos in Jinzhai county was obtained by superposition of suitable altitude distribution area, MaxEnt analysis and area extracted from remote sensing image, which provided data support for the planting planning of P. cocos in Jinzhai county.

Autophagy can protect stressed cancer cell by degradation of damaged proteins and organelles. However, the regulatory mechanisms behind this cellular process remain incompletely understood. Here, we demonstrate that RSK2 (p90 ribosomal S6 kinase 2) plays a critical role in ER stress-induced autophagy in breast cancer cells. We demonstrated that the promotive effect of RSK2 on autophagy resulted from directly binding of AMPKα2 in nucleus and phosphorylating it at Thr172 residue. IRE1α, an ER membrane-associated protein mediating unfolded protein response (UPR), is required for transducing the signal for activation of ERK1/2-RSK2 under ER stress. Suppression of autophagy by knockdown of RSK2 enhanced the sensitivity of breast cancer cells to ER stress both in vitro and in vivo. Furthermore, we demonstrated that inhibition of RSK2-mediated autophagy rendered breast cancer cells more sensitive to paclitaxel, a chemotherapeutic agent that induces ER stress-mediated cell death. This study identifies RSK2 as a novel controller of autophagy in tumor cells and suggests that targeting RSK2 can be exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer.

Objective: To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors. Methods: Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children's Medical Center, Shanghai Jiaotong University and Singapore KK Women's and Children's Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods. Results: There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months. Conclusions: NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.

Objective: To study the differences in the bone marrow histopathology between acquired aplastic anemia (AAA) in children and refractory cytopenia of childhood (RCC) to facilitate their diagnoses and differential diagnosis. Methods: The clinical data and bone marrow biopsies of the RCC and AAA cases diagnosed from January 2008 to December 2018 in Xinhua Hospital, Shanghai Jiaotong University School of Medicine and Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine were analyzed. Results: A total of 71 AAA and 79 RCC cases were analyzed. There were 52 males and 19 females, age ranged 1.0-15.0 years (median, 8.9 years) in the AAA group, and 53 males and 26 females, age ranged 0.5-16.0 years (median, 5.0 years) in the RCC group. All the biopsy specimens of AAA patients had severe hypocellularity; the cellularity of 88.7% (63/71) specimens was under 5.0%, and 11.3%(8/71) was 5%-24%. None of the AAA specimens showed any dysplastic change. All the biopsy specimens of RCC patients had hypocellularity, including 94.9%(75/79) of the specimens with a cellularity of 5%-50%. All of the RCC specimens showed a patchy distribution of hematopoiesis. A dysplastic change of erythroid cells and micromegakaryocytes was found in 40.5% (32/79) and in 60.8% (48/79) of the RCC cases, respectively. Conclusions: The degree of hypocellularity, the distribution pattern of hematopoiesis, the cell composition and localization of erythroid cell clusters and the appearance of micromegaryocytes could help the diagnosis and differential diagnosis of AAA and RCC.

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy ( n= 21), primary nephrectomy ( n= 41), post-chemotherapy nephrectomy/resection ( n= 18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) ( n= 11). The specimens of core biopsy and primary nephrectomy ( n= 62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk ( n= 0), intermediate risk ( n= 10) and high risk ( n= 2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk ( n= 0), intermediate risk ( n= 5) and high risk ( n= 1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

Endothelium-dependent vasorelaxation is partly mediated by small-conductance (SK3) and intermediate-conductance Ca 2+ -activated K + channels (SK4) in the endothelium that results in endothelium-dependent hyperpolarization (EDH). Apart from the electrical propagation through myoendothelial gap junctions, the K + released from the endothelium facilitates EDH by increasing inward rectifier K + channel (Kir) conductance in smooth muscle cells. The EDH-dependent relaxation of coronary artery (CA) and Kir current in smooth muscle cells (CASMCs) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart. In spontaneously hypertensive (SHR) and control (WKY) rats, we found attenuation of the CA relaxation by activators of SK3 and SK4 (NS309 and 1-EBIO) in SHR. In isolated CASMCs, whole-cell patch-clamp study revealed larger I Kir in SHR than WKY, whereas the myocytes of skeletal and cerebral arteries showed smaller I Kir in SHR than WKY. While the treatment with I Kir inhibitor (0.1 mmol/L Ba 2+ ) alone did not affect the WKY-CA, the SHR-CA showed significant contractile response, suggesting relaxing influence of the higher I K ir in the CASMCs of SHR. Furthermore, the attenuation of NS309-induced relaxation of CA by the combined treatment with 0.1 mmol/L Ba 2+ was more prominent in SHR than WKY. Our study firstly shows a distinct increase of I K ir in the CASMCs of SHR, which could partly compensate for the attenuated relaxation via endothelial SK3 and SK4., (© 2019 John Wiley & Sons Australia, Ltd.)

Purpose : To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. Methods : Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ERα were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ERα (-) breast cancer cells were tested both in vivo and in vitro . Results : UCH-L1 expression was conversely correlated with ERα status in breast cancer, and the negative regulatory effect of UCH-L1 on ERα was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ERα transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ERα caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ERα (-) breast cancer both in vivo and in vitro . Conclusions : Our results reveal an important role of UCH-L1 in modulating ERα status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In vascular smooth muscle, K + channels, such as voltage-gated K + channels (Kv), inward-rectifier K + channels (Kir), and big-conductance Ca 2+ -activated K + channels (BK Ca ), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (I Kv and I Kir ) in the left (LCSMCs), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) I Kv was larger in RCSMCs than that in SCSMCs and LCSMCs, (2) I Kv inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) I Kir was smaller in SCSMCs than that in RCSMCs and LCSMCs, and (4) I BKCa did not differ between branches. Moreover, in PAH rats, I Kir and I Kv decreased in SCSMCs, but not in RCSMCs or LCSMCs, and I BKCa did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in I Kv and I Kir occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller I Kir in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K + concentration under increased activity of the myocardium., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest., (Copyright © 2020 The Korean Physiological Society and The Korean Society of Pharmacology.)

Objective: Various studies have shown that aberrant expression of circular RNAs (circRNAs) has a pivotal role in multifarious cancers. However, the role of circRNAs in hepatoblastoma (HB) is not clearly understood. In the present study, we attempted to explore the underlying mechanism of hsa_cric_0000594 in HB along with its clinical importance., Patients and Methods: In our research, the expression pattern of hsa_circ_0000594 in HB tissues and matched normal liver tissues was determined by in situ hybridization and RT-qPCR. Proliferation, viability, migration, and apoptosis of HB cell lines were detected via Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays. The interaction of hsa_circ_0000594 with miR-217 was investigated by Dual-Luciferase reporter assay., Results: Expression levels of hsa_circ_0000594 were significantly upregulated in HB tissues compared with those in paired normal liver tissues and showed a clear association with the subtype of HB. The knockdown of hsa_circ_0000594 inhibited the malignant phenotype of HB. Bioinformatics analysis suggests that sirtuin 1 (SIRT1) may serve as a target gene of miR-217., Conclusions: Mechanically, hsa_circ_0000594 was identified to have a critical role in HB development through the hsa_circ_0000594/mir-217/SIRT1 regulatory axis, which might become a novel diagnostic marker and potential therapeutic target in HB.

Moutan Cortex is one kind of famous medicinal materials. The dry root bark of Paeonia ostii which is a genuine medicinal material produced in Tongling,Anhui province,and later was introduced to Heze,Shandong province and Bozhou,Anhui province.Dangshan county is located at the northern end of Anhui province and adjacent to Shandong province. Its medicinal seedlings were came from Heze,Shandong province. At present,there is a lack of scientific investigation on the planting area of P. ostii in north China plain. On the basis of field investigation and remote sensing technology,through the data source provided by the remote sensing image of " Resources 3"( ZY-3),combined with the biological characteristics of P. ostii,the planting area of P. ostii in Dangshan county was extracted by field investigation and supervisory classification. The supervise classification method with the highest interpretation accuracy so far,the overall accuracy was 97. 81%,Kappa coefficient 0. 96. The results showed that the remote sensing classification method based on the maximum likelihood classification could extract P. ostii plots in the study area effectively. This study provides a scientific basis for the protection and rational utilization of traditional Chinese medicine resources,the development policy of traditional Chinese medicine industry and the long-term development plan in Dangshan county,and provides technical support for the poverty alleviation of traditional Chinese medicine industry in Dangshan county. It provides scientific reference for the application of remote sensing technology to investigate the planting area of P. ostii in in north China plain.