Identifying a potentially invasive population in the native range of a species: The enlightenment from the phylogeography of the yellow spotted stink bug, Erthesina fullo (Hemiptera: Pentatomidae).

The yellow spotted stink bug (YSSB), Erthesina fullo (Thunberg, 1783) is an important Asian pest that has recently successfully invaded Europe and an excellent material for research on the initial stage of biological invasion. Here, we reported the native evolutionary history, recent invasion history, and potential invasion threats of YSSB for the first time based on population genetic methods [using double digest restriction-site associated DNA (ddRAD) data and mitochondrial COI and CYTB] and ecological niche modelling. The results showed that four lineages (east, west, southwest, and Hainan Island) were established in the native range with a strong east-west differentiation phylogeographical structure, and the violent climate fluctuation might cause population divergence during the Middle and Upper Pleistocene. In addition, land bridges and monsoon promote dispersal and directional genetic exchanging between island populations and neighboring continental populations. The east lineage (EA) was identified as the source of invasion in Albania. EA had the widest geographical distribution among all other lineages, with a star-like haplotype network with the main haplotype as the core. It also had a rapid population expansion history, indicating that the source lineage might have stronger diffusion ability and adaptability. Our findings provided a significant biological basis for fine tracking of invasive source at the lineage or population level and promote early invasion warning of potential invasive species on a much subtler lineage level.

Jungian Analysis of the Chinese Mythological Image of Sun Wukong.

This paper examines the symbolism of the cultural image Sun Wukong (the Monkey King), a Chinese legendary hero, and how it influenced an eight-year-old boy's psychic development. Through an analysis of Sun Wukong's life from his birth to attaining Buddhahood, a three-phase healing process is identified in Sun Wukong's tale and the psychotherapeutic process: "naming and initiating," "nurturing and taming," and "transforming and transcending," proposed by Dr. Heyong Shen. Sandplay visually highlighted these key clinical changes in conscious awareness and developmental behaviour influencing the boy's individuation process. Images found either in cultural traditions or spontaneously emerging from the unconscious in individuals are of significance in human life, offering pathways to psychic healing and development. Further, myths and cultural resources used in clinical work demonstrate that having cultural competency is invaluable in Jungian analysis. Pathogenic and health-maintenance factors of culture can be explored in future clinical practice and research.

Cet article étudie le symbolisme de l'image culturelle d'un héros légendaire chinois; Sun Wukong (le roi singe). L'article explore comment cette image a influencé le développement psychique d'un garçon de huit ans. À travers une analyse de la vie de Sun Wukong depuis sa naissance jusqu'à ce qu'il atteigne la bouddhéité, un processus de guérison en trois phases est identifié dans le conte de Sun Wukong et dans le processus psychothérapeutique, et proposé par le Dr Heyong Shen : « nommer et initier ¼, « apprivoiser et nourrir ¼ et « transformer et transcender ¼. La thérapie par le jeu de sable a ensuite mis en évidence visuellement ces changements cliniques clés dans la prise de conscience et le comportement développemental, qui ont influencé le processus d'individuation du garçon. Les images trouvées dans les traditions culturelles ou qui émergent spontanément de l'inconscient chez les individus sont importantes dans la vie des êtres humains : elles fournissent des voies de guérison et de développement psychiques. De plus, les mythes et les ressources culturelles utilisés dans le travail clinique montrent que la compétence culturelle est inestimable dans l'analyse jungienne. Les facteurs pathogènes et les facteurs de maintien de la santé - présents dans la culture - peuvent être explorés dans la pratique clinique et la recherche futures.

Este artículo explora el simbolismo de la imagen cultural de Sun Wukong (el Rey Mono), un héroe legendario chino, y cómo influyó en el desarrollo psíquico de un niño de ocho años. A través de un análisis de la vida de Sun Wukong desde su nacimiento hasta alcanzar la Budeidad, se identifica un proceso de curación en tres fases en el cuento de Sun Wukong y en el proceso psicoterapéutico: "nombrar e iniciar", "domar y nutrir" y "transformar y trascender", propuestos por el Dr. Heyong Shen. A continuación, el juego de arena puso de relieve visualmente estos cambios clínicos en la conciencia y en el desarrollo del comportamiento, influyendo en el proceso de individuación del niño. Las imágenes que se encuentran tanto en las tradiciones culturales, como las que que emergen espontáneamente del inconsciente de los individuos son importantes en la vida humana, ya que ofrecen vías para la curación psíquica y el desarrollo. Además, los mitos y los recursos culturales utilizados en el trabajo clínico demuestran que tener competencia cultural es inestimable en el análisis junguiano. Los factores patógenos y de mantenimiento de la salud de la cultura pueden explorarse en la práctica clínica y la investigación futuras.

Deep Learning-Enabled Morphometric Analysis for Toxicity Screening Using Zebrafish Larvae.

Toxicology studies heavily rely on morphometric analysis to detect abnormalities and diagnose disease processes. The emergence of ever-increasing varieties of environmental pollutants makes it difficult to perform timely assessments, especially using in vivo models. Herein, we propose a deep learning-based morphometric analysis (DLMA) to quantitatively identify eight abnormal phenotypes (head hemorrhage, jaw malformation, uninflated swim bladder, pericardial edema, yolk edema, bent spine, dead, unhatched) and eight vital organ features (eye, head, jaw, heart, yolk, swim bladder, body length, and curvature) of zebrafish larvae. A data set composed of 2532 bright-field micrographs of zebrafish larvae at 120 h post fertilization was generated from toxicity screening of three categories of chemicals, i.e., endocrine disruptors (perfluorooctanesulfonate and bisphenol A), heavy metals (CdCl2 and PbI2), and emerging organic pollutants (acetaminophen, 2,7-dibromocarbazole, 3-monobromocarbazo, 3,6-dibromocarbazole, and 1,3,6,8-tetrabromocarbazo). Two typical deep learning models, one-stage and two-stage models (TensorMask, Mask R-CNN), were trained to implement phenotypic feature classification and segmentation. The accuracy was statistically validated with a mean average precision >0.93 in unlabeled data sets and a mean accuracy >0.86 in previously published data sets. Such a method effectively enables subjective morphometric analysis of zebrafish larvae to achieve efficient hazard identification of both chemicals and environmental pollutants.

Death Anxiety During COVID-19 and its Related Factors among Chinese Elderly People.

This study aimed at investigating death anxiety and its related factors in Chinese elderly people during COVID-19. This study totally interviewed 264 participants from four cities in different regions of China. Death anxiety scale (DAS), NEO-Five-Factor Inventory (Neo-FFI) and Brief COPE were scored on the basis of one-on-one interviews. Quarantine experience didn't make significant difference in death anxiety among the elderly; Elderly people with high death anxiety had higher scores of neuroticism, and were more likely to use a Behavior Disengagement coping strategy; Multiple linear regression analysis showed that neuroticism, openness and COVID impact predicted 44.6% of the variance in the death anxiety among elderly people. The results support both theories of vulnerability-stress model and terror management theory (TMT). In the post-epidemic era, we suggest to pay attention to the mental health status of elderly people with personality susceptibility to handling the stress of infection badly.

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer.

As the third most common cancer and the second leading cause of cancer death worldwide, colorectal cancer (CRC) poses a serious threat to people's health. In recent years, circRNA has been widely reported as a new biomarker in CRC, but a comprehensive summary and analysis is lacking. This study aims to evaluate the diagnostic, therapeutic and prognostic significance of circRNAs in CRC by systematically analysing their expression patterns, biological functions and clinical significance in CRC. The literature on circRNA in CRC was searched in the PubMed database and included for analysis after screening according to strict inclusion and exclusion criteria. The UALCAN online tool was used to obtain host gene expression data. The miRTargetLink 2.0 was used to predict target genes for miRNAs action in CRC patients. Cytoscape was used to construct circRNA-miRNA-mRNA interaction networks. From the 236 included papers, we identified 217 circRNAs and their associated 108 host genes and 145 miRNAs. Among the 145 miRNAs, 27 miRNAs had no corresponding target genes. After prediction of target genes and differential analysis, a total of 25 target genes were obtained and a circRNA-miRNA-mRNA interaction network was constructed. Among the 217 circRNAs, 74 were associated with diagnosis, 160 with treatment and 51 with prognosis. And 154 of them function as oncogenes while 58 as tumour suppressor genes. In addition, these circRNAs include 32 exosomal circRNAs, which have unique advantages as biomarkers. In total, we summarize and analyze the expression patterns, biological functions and clinical significance of circRNAs in CRC. In addition, we constructed some new circRNA-miRNA-mRNA regulatory axes based on the miRNAs sponged by circRNAs.

The first complete mitochondrial genome of Dufouriellini (Hemiptera: Anthocoridae) and implications for its phylogenetic position.

The mitochondrial genome (mitogenome) is extensively used to better understand the phylogenetic relationships within the family level, but there are still limited representations at the tribe level of Anthocoridae. Here we describe the first complete mitogenome of Dufouriellini. The mitogenome of Cardiastethus sp. is 15,209 bp in size, containing 13 typical protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and a control region. All genes are arranged in the same gene order as the most other known cimicomorphan mitogenomes. The phylogenetic relationships based on mitogenomes using Bayesian inference and maximum likelihood methods show that Dufouriellini is sister to Anthocorini, and then both of them together form sister group with Oriini. The monophyly of each superfamily of Cimicomorpha is generally well supported. Reduvioidea is basal within Cimicomorpha. The topology of the remaining superfamily is as follows: (Miroidea + (Cimicoidea + (Velocipedoidea + Nabioidea))). This study will help to enhance our understanding of mitochondrial genomic evolution and phylogenetic relationships in the tribe level of Anthocoridae and also superfamily level of Cimicomorpha.

An Analysis of the Latent Class and Influencing Factors of Death Anxiety Among Han Chinese and Tibetan College Students.

In this study, 349 Han and 217 Tibetan college students were investigated via the Templer Death Anxiety Scale in order to assess the potential class and influencing factors of death anxiety among them. In addition, Mplus software was used to analyse the latent categories of their death anxiety, and an R3STEP approach was adopted to perform a multinomial logistic regression of its influencing factors. Whilst the results of the former indicated that there are two latent classes, respectively, defined as 'high death anxiety type' (Han 65.20%; Tibetan 30.30%) and 'low death anxiety type' (Han 34.80%; Tibetan 69.70%), the latter demonstrated that compared with the 'low death anxiety type', the occurrence ratio of the 'high death anxiety type' was 47.00 and 34.04 percentage points higher with each increase in age. Furthermore, the stress and anxiety of Han and Tibetan college students were found to constitute factors that affect death anxiety. More specifically, the death anxiety of Tibetan college students was determined to be deeply influenced by a belief in the afterlife.

The phylogenic position of aschiphasmatidae in euphasmatodea based on mitochondrial genomic evidence.

The mitochondrial genome (mitogenome) has been regarded as significant source of data to better understand the phylogenetic relationships within the Euphasmatodea, but no mitogenome in Aschiphasmatoidea has been sequenced to date. In this study, two mitogenomes of Orthomeria smaragdinum and Nanhuaphasma hamicercum of Aschiphasmatidae were sequenced and annotated for the first time. The same mitochondrial gene rearrangement structure was present in the two mitogenomes sequenced, showing as the translocation of tRNA-Arg and tRNA-Asn, which conformed to the tandem duplication-random loss and could be used as a possible synapomorphy for Aschiphasmatidae. The phylogenetic results based on the maximum likelihood (ML) and bayesian inference (BI) methods both showed that Aschiphasmatidae and Neophasmatodea in Euphasmatodea are sister taxa. Although the monophyly of Oriophasmata, Occidophasmata, Diapheromeridae, Phasmatidae, Lonchodidae and Bacilloidea has not been solved, the monophyly of Neophasmatodea and Phyllioidea was well supported.

Low-loss and high-resolution mechanical mode tuning in microspheres.

Lack of tunability impedes the wide application of optomechanical systems; however, little research exists on mechanical frequency tuning. Herein, ultra-fine low-loss dynamical mechanical frequency tuning is achieved by compressing a microsphere along the axial direction. The tuning resolution reaches approximately 4% of the mechanical linewidth, and the variation range of the mechanical quality factor (Qm) is within 2.9% of the untouched Qm. The roles of geometric deformation, spring effect, and stiffness were also evaluated through simulation and experimental analysis. Furthermore, sine function modulation was displayed, with a Pearson coefficient exceeding 99.3%, to achieve arbitrary-function mechanical resonance tuning. This method paves the way for scalable optomechanical applications, such as mechanical vibration synchronization or optomechanics-based optical wavelength conversion.

Review and Prospect of the Research on Occupational Health Psychology of Casino Employees.

The occupational specialty of casino employees brings about the problem of long-standing severe emotional exhaustion and stress management challenges. Therefore, it is of great significance to pay attention to their occupational health psychology (Du & Li, in Psych Res 7(1):46-50, 2014). Based on the relevant researches on occupational health psychology of casino employees at home and abroad in recent years, this paper reviews and outlines the previous research results in a systematic way from environmental and occupational, organizational as well as individual dimensions, and figures out the factors that may affect the occupational health psychology of casino employees, and further expounds the psychological and behavioral effects of these factors on employees (including job burnout, organizational commitment, job satisfaction, employees' problematic gambling behavior, etc.), with the purpose of getting a deeper understanding of why occupational health psychology of casino employees can affect customer satisfaction, loyalty and casino profits ultimately. On this basis, three suggestions are put forward for the optimization of human resource management in casinos through the lens of occupational health psychology. In the end, the paper points out some shortcomings of existing studies and the trend for future study that can expand and deepen relevant variables and research subjects that affect the occupational health psychology of casino employees on the basis of comprehensive review.

Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellarin (Scu) is one of the main active ingredients of Erigeron breviscapus (Vant.) Hand.-Mazz which has been used to treat cardiovascular disease including vascular dysfunction caused by diabetes. Scu also has a protective effect on vascular endothelial cells against hyperglycemia. However, molecular mechanisms underlying this effect are not clear. AIM OF THE STUDY: This aim of this study was to investigate the effect of Scu on human umbilical vein endothelial cells (HUVECs) injury induced by high glucose (HG), especially the regulation of PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. MATERIALS AND METHODS: HUVECs were exposed to HG to induce vascular endothelial cells injury in vitro. Cell viability was assessed by MTT assay. The extent of cell apoptosis was measured by Hoechst staining and flow cytometry. Mitophagy was assayed by fluorescent immunostaining, transmission electron microscope and immunoblot. Besides, virtual docking was conducted to validate the interaction of PINK1 protein and Scu. RESULTS: We found that Scu significantly increased cell viability in HG-treated HUVECs. Scu reduces the expression of Bcl-2, Bax and cytochrome C (Cyt.c) to inhibit apoptosis through a mitochondria-dependent pathway. Meanwhile, Scu improved the overload of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and SOD2 protein expression, and reversed the collapse of mitochondrial membrane potential. Besides, Scu increased autophagic flux, improved the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 II), Beclin 1 and autophagy-related gene 5 (Atg 5) and decreased the expression of Sequestosome1/P62 in HG-treated HUVECs. Furthermore, Scu improved the expressions of PINK1, Parkin, and Mitofusin2, which revealed the enhancement of mitophagy. Moreover, the beneficial effects of Scu on HG-induced low expression of Parkin, overproduction of ROS, and over expressions of P62, Cyt.c and Cleaved caspase-3 were weakened by PINK1 gene knockdown. Molecular docking suggested good interaction of Scu and PINK1 protein. CONCLUSION: These results suggest that Scu may protect vascular endothelial cells against hyperglycemia-induced injury by up-regulating mitophagy via PINK1/Parkin signal pathway.

Association of Interleukin-6 Levels with Morbidity and Mortality in Patients with Coronavirus Disease 2019 (COVID-19).

The prognostic value of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) needs to be clarified. In this retrospective study, COVID-19 patients treated at Renmin Hospital of Wuhan University from January 7 to February 8, 2020 with measurements of serum IL-6 levels within 1 week after admission were included. Data regarding demographics, clinical characteristics, laboratory tests, complications, and outcomes were collected and analyzed. Sixty-six patients diagnosed with COVID-19 were included in this study (31 patients were females). They were divided into a normal group (serum IL-6 <10 pg/mL, n = 35) and an abnormal group (serum IL-6 <10 pg/mL, n = 31). Compared with the normal group, the incidence of critical cases (P <0.001), acute respiratory distress syndrome (ARDS) (P = 0.001), acute cardiac injury (P = 0.002), cardiac insufficiency (P = 0.039), mechanical ventilation rate (P = 0.002), and mortality (P = 0.021) was significantly increased in the abnormal group. Serum IL-6 concentration was an independent predictor of fatal outcome (P = 0.04). The optimal cutoff value of serum IL-6 concentration for predicting fatal outcomes was 26.09 pg/mL (P <0.001). In COVID-19, elevated serum IL-6 levels were associated with critical illness, use of mechanical ventilation, and complications, including heart injury and ARDS, and could predict a fatal outcome. Early detection of serum IL-6 levels after admission should be necessary in COVID-19 patients.

Self-Healing and Mechanical Properties of Thermoplastic Polyurethane/Eugenol-Based Phenoxy Resin Blends via Exchange Reactions.

The possibility of exchange reactions and thermal self-healing in blends of thermoplastic polyurethane (TPU) and phenoxy resin was investigated herein. The analyses were based on characterization obtained via differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), dynamic mechanical analysis (DMA), and tensile test. A new phenoxy resin was synthesized from eugenol, and blends with different types of TPU were prepared to investigate the exchange reaction, thermal self-healing, and mechanical properties. The influence of phenoxy resin content on the mechanical behavior and healing efficiency was studied. Improvement of storage modulus owing to the increase of phenoxy resin content was observed. Results suggest that the exchange reaction between phenoxy- and ester-type TPU occurred during thermal treatment. However, little exchange occurred between phenoxy resin and ether-type TPU. Specifically, only ester-type TPU exhibited a significant exchange reaction in the phenoxy resin blend. Furthermore, in the presence of a catalyst (e.g., zinc acetate), the exchange reaction readily occurred, and the healing efficiency improved by the addition of the catalyst and increase in the phenoxy content.

Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP-1c suppression.

High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)-fed mice. In vitro, we found that Scu decreased insulin-dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA-treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n-SREBP-1c protein level and also reduced lipid accumulation via the mTOR-dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD-fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP-1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR-dependent pathway through SREBP-1c suppression.

New Mycodiplosis gall midge (Diptera: Cecidomyiidae) feeding on fungal rusts (Fungi: Pucciniomycetes) that are pathogenic on cultured plants.

Larvae of a gall midge were found feeding on the fungal rust Maravalia pterocarpi (Pucciniomycetes: Pucciniales: Chaconiaceae) infesting the economically important sua tree Dalbergia tonkinensis (Fabaceae) on Hainan Island, China. The adults, pupae and larvae were collected, their morphology was studied and a segment of the Cytochrome Oxidase unit I (COI) mitochondrial gene was sequenced. The gall midge proved to be a species new to science that belongs to the genus Mycodiplosis (Diptera: Cecdiomyiidae). Comparison of the sequence to published Cecdiomyiidae sequences revealed that, despite being undescribed and unnamed, it was previously found in east and south-east Asia to feed on several rust species: Puccinia coronata (Pucciniomycetes: Pucciniales: Pucciniaceae) that develops on Lolium multiflorum (Poaceae), Puccinia sp. on Zea mays (Poaceae), Puccinia arachidis on Arachis hypogaea (Fabaceae) and Puccinia allii on Allium fistulosum (Amaryllidaceae). The new species is described and named here Mycodiplosis puccinivora Jiao, Bu Kolesik. It occurs in China, Japan, Thailand, Bangladesh and possibly Malaysia and Australia. In Hainan it has four to five generations per year.

Characteristics of Self-Healable Copolymers of Styrene and Eugenol Terminated Polyurethane Prepolymer.

With limited biomass that can be currently utilized as a renewable resource, it is important to develop a method to convert biomass into materials that can replace fossil fuel product. In this paper, eugenol, a bio-based allyl chain-substituted guaiacol, was used to synthesize self-healable copolymers. Eugenol terminated polyurethane prepolymer (ETPU) was synthesized from eugenol and polyurethane prepolymers terminated with isocyanate groups. ETPU contained two allyl groups. Self-healing copolymer networks were obtained by copolymerization of ETPU and styrene monomer via free radical polymerization. Effects of ETPU content on the properties of copolymers were then studied. These copolymers containing ETPU exhibited good thermal stability and mechanical properties. These copolymers showed higher tensile strength and elongation at break than PS. Their maximum tensile strength reached 19 MPa. In addition, these copolymers showed self-healing property at elevated temperature due to the reversible nature of urethane units in ETPU.

Effects of UV-B radiation on the survival, egg hatchability and transcript expression of antioxidant enzymes in a high-temperature adapted strain of Neoseiulus barkeri.

Biological control of spider mites in hot and dry weather is a serious technical issue. A high-temperature adapted strain (HTAS) of the predatory mite Neoseiulus barkeri Hughes was selected from its conventional strain (CS), via long-term heat acclimation and frequent heat hardenings in our previous studies. However, the environment of high temperature is usually associated with enhanced ultraviolet (UV) radiation. In the present study, the physiological effects of UV-B radiation on survival rate and egg damage of N. barkeri were investigated, as well as the activities and expression profiles of antioxidant enzymes to UV-B radiation stress. UV-B radiation had deleterious effects on egg hatchability and survival of N. barkeri. Adults of the HTAS strain were less UV-B resistant than those of the CS strain; they also had lower levels of enzymatic activity of superoxide dismutase (SOD) and catalase against oxidative damage and weaker upregulation of SOD genes. The mRNA expression of three SOD genes of CS adult females immediately increased whereas that of HTAS showed almost no difference under UV-B stress for 1 h. The results showed the HTAS of N. barkeri had lower fitness under UV-B stress compared with the CS of N. barkeri. These results suggested that long-term heat acclimation may exert a profound impact on the developmental physiology of N. barkeri.

Effects of Isosorbide Incorporation into Flexible Polyurethane Foams: Reversible Urethane Linkages and Antioxidant Activity.

Isosorbide (ISB), a nontoxic bio-based bicyclic diol composed from two fuzed furans, was incorporated into the preparation of flexible polyurethane foams (FPUFs) for use as a cell opener and to impart antioxidant properties to the resulting foam. A novel method for cell opening was designed based on the anticipated reversibility of the urethane linkages formed by ISB with isocyanate. FPUFs containing various amounts of ISB (up to 5 wt%) were successfully prepared without any noticeable deterioration in the appearance and physical properties of the resulting foams. The air permeability of these resulting FPUFs was increased and this could be further improved by thermal treatment at 160 °C. The urethane units based on ISB enabled cell window opening, as anticipated, through the reversible urethane linkage. The ISB-containing FPUFs also demonstrated better antioxidant activity by impeding discoloration. Thus, ISB, a nontoxic, bio-based diol, can be a valuable raw material (or additive) for eco-friendly FPUFs without seriously compromising the physical properties of these FPUFs.

Peperomin E and its orally bioavailable analog induce oxidative stress-mediated apoptosis of acute myeloid leukemia progenitor cells by targeting thioredoxin reductase.

The early immature CD34+ acute myeloid leukemia (AML) cell subpopulation-acute myeloid leukemia progenitor cells (APCs), is often resistant to conventional chemotherapy, making them largely responsible for the relapse of AML. However, to date, the eradication of APCs remains a major challenge. We previously reported a naturally occurring secolignan- Peperomin E (PepE) and its analog 6-methyl (hydroxyethyl) amino-2, 6-dihydropeperomin E (DMAPE) that selectively target and induce oxidative stress-mediated apoptosis in KG-1a CD34+ cells (an APCs-like cell line) in vitro. We therefore further evaluated the efficacy and the mechanism of action of these compounds in this study. We found that PepE and DMAPE have similar potential to eliminate primary APCs, with no substantial toxicities to the normal cells in vitro and in vivo. Mechanistically, these agents selectively inhibit TrxR1, an antioxidant enzyme aberrantly expressed in APCs, by covalently binding to its selenocysteine residue at the C-terminal redox center. TrxR1 inhibition mediated by PepE (DMAPE) leads to the formation of cellular selenium compromised thioredoxin reductase-derived apoptotic protein (SecTRAP), oxidation of Trx, induction of oxidative stress and finally activation of apoptosis of APCs. Our results demonstrate a potential anti-APCs molecular target - TrxR1 and provide valuable insights into the mechanism underlying PepE (DMAPE)-induced cytotoxicity of APCs, and support the further preclinical investigations on PepE (DMAPE)-related therapies for the treatment of relapsed AML.

Clinopodium chinense Attenuates Palmitic Acid-Induced Vascular Endothelial Inflammation and Insulin Resistance through TLR4-Mediated NF- κ B and MAPK Pathways.

Elevated palmitic acid (PA) levels are associated with the development of inflammation, insulin resistance (IR) and endothelial dysfunction. Clinopodium chinense (Benth.) O. Kuntze has been shown to lower blood glucose and attenuate high glucose-induced vascular endothelial cells injury. In the present study we investigated the effects of ethyl acetate extract of C. chinense (CCE) on PA-induced inflammation and IR in the vascular endothelium and its molecular mechanism. We found that CCE significantly inhibited PA-induced toll-like receptor 4 (TLR4) expression in human umbilical vein endothelial cells (HUVECs). Consequently, this led to the inhibition of the following downstream adapted proteins myeloid differentiation primary response gene 88, Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon- ß and TNF receptor-associated factor 6. Moreover, CCE inhibited the phosphorylation of Ikappa B kinase ß , nuclear factor kappa-B (NF- κ B), c-Jun N-terminal kinase, extracellular regulated protein kinases, p38-mitogen-activated protein kinase (MAPK) and subsequently suppressed the release of tumor necrosis factor- α , interleukin-1 ß (IL-1 ß ) and IL-6. CCE also inhibited IRS-1 serine phosphorylation and ameliorated insulin-mediated tyrosine phosphorylation of IRS-1. Moreover, CCE restored serine/threonine kinase and endothelial nitric oxide synthase (eNOS) activation and thus increased insulin-mediated nitric oxide (NO) production in PA-treated HUVECs. This led to reverse insulin mediated endothelium-dependent relaxation, eNOS phosphorylation and NO production in PA-treated rat thoracic aortas. These results suggest that CCE can significantly inhibit the inflammatory response and alleviate impaired insulin signaling in the vascular endothelium by suppressing TLR4-mediated NF- κ B and MAPK pathways. Therefore, CCE can be considered as a potential therapeutic candidate for endothelial dysfunction associated with IR and diabetes.