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Welwitschia mirabilis, which is endemic to the Namib Desert, is the only living species within the family Welwitschiaceae. This species has an extremely long lifespan of up to 2,000 years and bears a single pair of opposite leaves that persist whilst alive. However, the underlying genetic mechanisms and evolution of the species remain poorly elucidated. Here, we report on a chromosome-level genome assembly for W. mirabilis, with a 6.30-Gb genome sequence and contig N50 of 27.50 Mb. In total, 39,019 protein-coding genes were predicted from the genome. Two brassinosteroid-related genes (BRI1 and CYCD3), key regulators of cell division and elongation, were strongly selected in W. mirabilis and may contribute to their long ever-growing leaves. Furthermore, 29 gene families in the mitogen-activated protein kinase signalling pathway showed significant expansion, which may contribute to the desert adaptations of the plant. Three positively selected genes (EHMT1, EIF4E, SOD2) may be involved in the mechanisms leading to long lifespan. Based on molecular clock dating and fossil calibrations, the divergence time of W. mirabilis and Gnetum montanum was estimated at ~123.5 million years ago. Reconstruction of population dynamics from genome data coincided well with the aridification of the Namib Desert. The genome sequence detailed in the current study provides insight into the evolution of W. mirabilis and should be an important resource for further study on gnetophyte and gymnosperm evolution.

Pica is defined as abnormal appetite or consumption of nonnutritive substances inappropriate for development. There is no consensus on the etiology of pica in animals. The present study investigated the status of serum minerals together with the hematological and biochemical parameters and antioxidant enzymes in horses with and without pica. Eight horses with pica and eight healthy horses were used in the study. The serum levels of calcium, phosphorus, copper, iron, the calcium/phosphorus ratio, and the copper/zinc ratio were lower in the pica group compared with the control group (P

Equine pregnancy is currently diagnosed by rectal palpation, ultrasonographic examination, or by measuring changes in hormones in the blood. In the present study, we identified proteins that are differentially expressed in the sera of early pregnant and non-pregnant mares in order to develop a novel method for diagnosing equine pregnancy. Serum samples were obtained from 18 adult mares, pregnancy at day 32 after ovulation (n = 9) and in diestrus (n = 9). Proteomic analysis of the samples was conducted using liquid chromatography-electrospray ionization-tandem mass spectrometry. We identified 467 proteins from a total of 3514 peptides. Thirty-two proteins (15 upregulated and 17 downregulated) were significantly differentially expressed between the two groups. The Gene Ontology enrichment analysis revealed that they are related to extracellular matrix assembly, blood coagulation, and hemostasis, and the prominent molecular functions were integrin binding, cell adhesion molecule binding, and glycine C-acetyltransferase activity. The pathway analysis of Kyoto Encyclopaedia of Genes and Genomes showed that the top three pathways identified were glycine, serine, and threonine metabolism; cysteine and methionine metabolism; and ether lipid metabolism. The selected five serum proteins were newly potential candidates for pregnancy diagnosis in mares.

Oxidative stress is an early major pathological feature after subarachnoid hemorrhage (SAH) and involves in the development of acute brain injury, neuronal apoptosis and cerebral vasospasm following SAH. Antioxidant stress is an effective way to improve the prognosis of SAH. Oleanolic acid is a widely used triterpenoid from plants, which has strong antioxidant activities, hepatoprotective, anti-inflammatory and anti-cancer activities. However, whether oleanolic acid exerts its anti-oxidant effect after SAH and the underlying mechanisms involved in it is unclear. In current study, the SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. We found OA treatment significantly reduced malondialdehyde levels, and increased the levels of superoxide dismutase, catalase and GSH-Px after SAH, and reduced many EBI-related indicators, including brain edema, BBB disruption, SAH grades, and neurological score. In addition, the activation of Nrf2/HO-1 pathway after SAH was also detected. And by using Nrf2 siRNA intracerebroventricular injections, apoptosis related factors downstream of Nrf2/HO-1 pathway were detected. By TUNEL staining, OA treatment obviously reduced neuronal apoptosis. Therefore, we suggest that OA could alleviate oxidative stress and reduce neuronal apoptosis through activating Nrf 2/HO-1 pathway.

Background In South-east Asia, Dipterocarpoideae is predominant in most mature forest communities, comprising around 20% of all trees. As large quantity and high quality wood are produced in many species, Dipterocarpoideae plants are the most important and valuable source in the timber market. The d-borneol is one of the essential oil components from Dipterocarpoideae (for example, Dryobalanops aromatica or Dipterocarpus turbinatus) and it is also an important traditional Chinese medicine (TCM) formulation known as “Bingpian” in Chinese, with antibacterial, analgesic and anti-inflammatory effects and can enhance anticancer efficiency. Methods In this study, we analyzed 20 chloroplast (cp) genomes characteristics of Dipterocarpoideae, including eleven newly reported genomes and nine cp genomes previously published elsewhere, then we explored the chloroplast genomic features, inverted repeats contraction and expansion, codon usage, amino acid frequency, the repeat sequences and selective pressure analyses. At last, we constructed phylogenetic relationships of Dipterocarpoideae and found the potential barcoding loci. Results The cp genome of this subfamily has a typical quadripartite structure and maintains a high degree of consistency among species. There were slightly more tandem repeats in cp genomes of Dipterocarpus and Vatica, and the psbH gene was subjected to positive selection in the common ancestor of all the 20 species of Dipterocarpoideae compared with three outgroups. Phylogenetic tree showed that genus Shorea was not a monophyletic group, some Shorea species and genus Parashorea are placed in one clade. In addition, the rpoC2 gene can be used as a potential marker to achieve accurate and rapid species identification in subfamily Dipterocarpoideae. Conclusions Dipterocarpoideae had similar cp genomic features and psbM, rbcL, psbH may function in the growth of Dipterocarpoideae. Phylogenetic analysis suggested new taxon treatment is needed for this subfamily indentification. In addition, rpoC2 is potential to be a barcoding gene to TCM distinguish.

The traditional neural network can not realize the invariance of image rotation and distortion well, so the attacker can cheat the neural network by adding tiny disturbance on the image. If signposts are attacked, automatic driving will be misguided, leading to disastrous consequences. This paper proposes a new adversarial sample defense model based on attention mechanism, which used LSTM network to get the key features. Firstly, we describe our model which recognizes an object through enough main characteristics. It can discard large parts of the noise distributed throughout the image area. Secondly, we show recognition process of the model, receiving adversarial samples and then outputting the salient mask image which can be classified correctly by neural networks in deep learning. At last, we designed experiments to test model effect on the traffic sign and the general picture. The experimental results show that our defense model can strongly defend adversarial examples.

The purpose of this study was to investigate the profile change of serum trace and major elements, and biochemical and hematological parameters in jennies during late pregnancy and early lactation. Twenty-five healthy Chinese Liaoxi jennies were used in late pregnancy and early lactation. Results showed that the levels of Fe, total protein (TP), and aspartate aminotransferase (AST) were highly variable interindividual among the jennies. Early lactating jennies showed significantly lower serum levels of K, Se, AST, total cholesterol (TC), and triglyceride than late pregnant jennies (P.05). Principal component analysis identified six and five principal components of serum mineral and biochemical parameters for late pregnant and early lactating jennies, respectively, which was supported by the cluster analysis findings. Strong clustering of serum Cu-Mn, iPhos-Se-TP, and Ca-Zn-alanine aminotransferase-TC was found in the late pregnant jennies, and strong clustering of serum Ca-Zn-Se-Mn-albumin, Na-Fe-AST-triglyceride, and K-Mg-Cu-TP was observed in the early lactating jennies. The study suggests a significant variation in the serum levels of mineral and biochemical parameters in late pregnant and early lactating jennies, which is valuable in estimating their physiological status and providing proper health care.

Essential information on the population dynamics and the health and welfare of Chinese donkeys is scarce. The objectives of this study were to describe the demographic characteristics, management and health care of a sample of donkeys under smallholder farm conditions of northeastern China. A cross-sectional survey of 731 randomly selected donkey owners on smallholder farms (1,658 donkeys) in 40 villages of northeastern China was conducted. Data on the composition and management of the donkeys and their routine health care were analyzed. The surveyed donkey population consisted of mostly (83.8%) jenny/filly donkeys with a mean age of 6.2 ± 5.0 years. Most (91.2%) of the farms kept 1–4 donkeys. The majority of donkeys were used for breeding and labor. Most (93.8%) of the farms did not have bedding, and their mean stable size was 17.7 ± 10.1 m2. All of the animals were turned out for at least part of the year. The mean size of the turnout areas on the farms was 17.8 m2. The condition of 12.5% of the donkeys was evaluated as “poor” with a body condition score of 1 on a scale of 5. More than one third (37.9%) of the donkeys had never been dewormed. Also, none of them were ever vaccinated or received dental care from a veterinarian. Their hoofs were trimmed once (45.9%) or twice (27.6%) a year. Forty percent of the donkeys were reported to suffer from at least one medical problem in the preceding year. The most common medical problems were colic, respiratory disorders and skin conditions. Owners seemed to underestimate some of the most prevalent diseases in donkeys, suggesting that their knowledge of the management of donkeys, including routine healthcare practices should be improved to ensure the health and welfare of donkeys in northeastern China.

Vasogenic brain edema after subarachnoid hemorrhage (SAH) is an independent risk factor for death and poor prognosis. Disruption of the blood-brain barrier (BBB) is the main cause of vasogenic brain edema induced by SAH. Oleanolic acid (OA) is a natural pentacyclic triterpenoid with various biological functions. Previous studies have shown that prophylactic administration of OA could prevent the BBB disruption in autoimmune encephalomyelitis mice. In this context, we speculate that OA may play a neuroprotective role by protecting the integrity of the BBB and reducing vasogenic cerebral edema after SAH. To validate this hypothesis, a SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. The effects of OA on various physiological indexes were observed, including SAH grades, mortality, neurological function score, brain edema and BBB permeability. Related proteins of the brain endothelial cell junction complex were also detected, including tight junctions (TJs) and adherent junctions (AJs). Results showed that OA significantly reduced the permeability of BBB and relieved brain edema by increasing protein expression of TJs and AJs, and decreased the SAH grades by increasing the protein expression of heme oxygenase-1 (HO-1) in SAH rats. Additionally, we found OA could inhibit up-regulation of VEGF and the phosphorylation of p38 mitogen-activated protein kinase (MAPK), and suppress p38MAPK/VEGF/Src signaling pathway which involved in BBB disruption following SAH. From the experimental results, we speculate that OA effectively alleviated SAH-induced vasogenic edema by targeting p38 MAPK/VEGF/Src axis.

Deep profiling of glycosphingolipids and sphingomyelins in wild Cordyceps was carried out by using offline chromatographic enrichment followed by ultrahigh performance liquid chromatography-ultrahigh definition-quadrupole time-of-flight mass spectrometry (UHPLC-UHD-Q-TOF-MS). A total of 119 glycosphingolipids (72 new ones) and 87 sphingomyelins (43 new ones) were identified from wild Cordyceps on the basis of the accurate mass and MS/MS fragmentations, isotope patterns, sphingolipid (SPL) database matching, confirmation by SPL standards, and the reversed-phase liquid chromatographic retention rule. This study is the most comprehensive report on the identification of glycosphingolipids and sphingomyelins from fungus. A subsequent lipopolysaccharide-induced mouse splenic lymphocyte proliferation assay showed that the Cordyceps glycosphingolipid fraction exhibits higher immunosuppressive activity compared to that of Cordyceps sphingomyelins. Our findings provided insight into the chemical diversity of sphingolipids in Cordyceps and chemical evidence for the therapeutic application of wild Cordyceps.

The steroidal saponin DT-13 (25(R,S)-ruscogenin-1-O-[β-d-glucopyranosyl-(1 → 2)][β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside), one of the major active compounds of the herb Liriope muscari (Decne.), exhibits significant anti-inflammatory, anti-tumor and cardioprotective effects. This study aimed to explore the protective effect of DT-13 on endothelium through regulating of nitric oxide production induced by Tumor necrosis factor-α (TNF-α). The results demonstrated that DT-13 inhibited inflammatory cell infiltration and thus played a protective effect on endothelial cells in vivo, as shown by hematoxylin-eosin (H&E) staining and immunohistochemical staining. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that DT-13 could suppress the TNF-α-induced upregulation of reactive oxygen species (ROS), tumor necrosis factor receptor (TNFR), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and nitric oxide in vivo dose-dependently and suppressed production of nitric oxide in vitro as shown by DAF-FMDA. Western blotting results indicated that DT-13 could down-regulate phosphorylation of endothelial nitric oxide synthase (eNOS) significantly in TNF-α-induced human umbilical vein endothelial cells (HUVECs). Taken together, we speculate that DT-13 inhibits endothelium vascular inflammation through regulating nitric oxide production and the expression of ROS, TNFR, IL-8, MCP-1, which are associated with inflammation.

Discharging performances of supercooled salt hydrate PCM (phase change material) in the rounded rectangular storage unit are numerically investigated with the developed multiphase model. Comparisons are first made between supercooled Sodium acetate trihydrate (SAT, CH3COONa·3H2O) and Sodium thiosulfate pentahydrate (STP, Na2S2O3·5H2O). Effects of environment temperature for storage (t0), temperature of the working fluid (tf), the area – volume ratio of the unit (A/V) and PCM thermal conductivity are then analyzed. The results showed that STP has 8% less loss of latent heat during the triggering crystallization process whereas lower discharging rate than SAT due to the lower melting point. Decreasing t0 from 14 °C to 6 °C results in 9% more latent heat loss; decreasing tf from 38 °C to 30 °C also shortens the time period for heat release from 4h to 1.8h; higher A/V and k lead to the higher heat transfer rate, for A/V =200 m−1, the discharging time is 4.2h shorter than that for A/V =70 m−1; however, the effect of k is negligible when k is over 1 W m−1 K−1 due to the larger thermal resistance on the side of working fluid. The results provide guidance for design and application of supercooled SAT and STP in rounded rectangular units for energy storage in solar heating systems.

Multiphase model is set up and applied to perform a 3D transient CFD simulation on the discharging characteristics of supercooled PCM. Three typical processes are identified and analyzed, i.e. stable supercooling, triggering crystallization and regular solidification periods. The simulation is achieved by loading the source term in energy equation and phase transition term in volume fraction equation. PCM temperature, solid fraction (SF) and heat transfer rate (HTR) to the surroundings are monitored and analyzed during the three stages. It is found that there is little difference among the temperature and SF curves of different z-direction planes during the first two periods but they are distinct during the regular solidification period. For the triggering crystallization period, PCM temperature rises much rapidly up to the melting point within 30 s and SF increases up to 0.33 correspondingly. The heat loss is small in this short period and could be simplified as adiabatic. Variations of temperature and SF extend from up and side walls to the interior of the PCM unit. HTR curve fluctuates greatly throughout the three processes with highest value of 1420 W occurring in regular solidification period. The developed method can be used for parameter analysis of supercooled PCM thermal storage devices.

Apigenin (API) is a naturally occurring plant flavone that exhibits powerful antioxidant and antiapoptosis. Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The potential anti-oxidative and anti-apoptosis effects of API on EBI following SAH, however, have not been elucidated. The aim of this study was to assess whether API alleviates EBI after SAH via its anti-oxidative and anti-apoptotic effects. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 24h after SAH. Our data demonstrated that administration of API could significantly alleviate EBI (including neurological deficiency, brain edema, blood-brain barrier permeability, and cortical cell apoptosis) after SAH in rats. Meanwhile, API treatment reduced the reactive oxygen species (ROS) level and the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO), elevated the ratio of glutathione (GSH) and oxidized glutathione (GSSG), and increased the amount of super-oxide dismutase (SOD) and hydrogen peroxide in brain cortex at 24h following SAH. Moreover, API treatment inhibited SAH-induced the expression of Bax and caspase-3, significantly reduced neuronal apoptosis. Collectively, API exerts its neuroprotective effect likely through the dual activities of anti-oxidation and anti-apoptosis, at least partly. These data provide a basic platform to consider API may be safely used as a potential drug for treatment of SAH.

To investigate the association of early serum calprotectin (S100A8/A9) level with disease severity and prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH).Serum samples were collected from 54 patients with aSAH (within 48 hours of onset) and 54 health controls. Levels of serum calprotectin were determined by enzyme linked immunosorbent assay. The clinical data of aSAH patients were collected. The prognosis was evaluated by modified Rankin scale at 3 months. Univariate and multivariable logistic regression analysis, bivariate correlation analysis and receiver operating characteristic (ROC) curve analysis were used respectively.Serum calprotectin levels were significantly higher in aSAH patients than that in healthy controls (P.001). The clinical severity was also significantly correlated with the level of serum calprotectin. Patients with poor prognosis at 3 months showed higher serum calprotectin levels within 48 hours of onset than that in patients with good prognosis (P = .002). The level of serum calprotectin within 48 hours was related to the complications of secondary pneumonia. Serum calprotectin can be used as an independent predictor for delayed cerebral ischemia (DCI) after aSAH and poor prognosis in patients with aSAH at 3 months. The ROC curve showed the cutoff value of calprotectin for predicting poor prognosis at 3 months was 6020 pg/ml (sensitivity: 53.57%, specificity: 96.15%), and the cutoff value for predicting DCI was 5275 pg/ml (sensitivity: 68.42%, specificity: 82.86%).Serum calprotectin concentrations within 48 hours after onset was significantly correlated with the clinical severity and the poor prognosis at 3 months in aSAH patients, suggesting that serum calprotectin may be a biomarker for early prediction of prognosis and complications in patients with aSAH and calprotectin may be a target for the treatment of aSAH.

Author(s): Li, Chengguo; Han, Yuwei; Jiang, Yu; Yang, Jiacheng; Karavalakis, Georgie; Durbin, Thomas D; Johnson, Kent

With the continuous development of China's economy and technology, people's living standard and average income have improved, and more and more people participate in venture capital and financial activities.Compared with general financial activities, venture capital has the characteristics of high investment, high risk and high return. It is aimed at people who have strong capital strength and is interested in investment. They often take the pursuit of high return as the internal driving force of investment, and determine their investment through the analysis of enterprises,through the way of investment in the enterprise, we can get part of the profits of the enterprise operation.This paper will discuss the general situation of venture capital, the problems of venture capital management under the condition of capital market and the specific strategies of venture capital management under the condition of capital market for reference.

Serum and plasma are commonly used in clinical practice considering the widely accepted fact that the "normal" protein expression pattern of a healthy animal changes under disease conditions. We herein used a label-free mass spectrometry-based quantitative proteomics approach to characterize the serum proteome of donkeys. A total of 277 unique proteins were identified from 2,388 unique peptides. Gene ontology analyses showed that the most frequent processes were related to metabolic activities and biological regulation, response to stimulus, and immune system processes. The main annotated areas of origin were the extracellular region, extracellular region part, and organelle, and their molecular functions included binding, catalytic activity, and molecular function regulator. Analyses using the Clusters of Orthologous Groups for Eukaryotic Complete Genomes database indicated that the identified proteins could be categorized into three main groups: signal transduction mechanisms, amino acid transport and metabolism, and defense mechanisms. Most of the unique proteins were associated with the complement and coagulation cascades, and they participated in several disease-related metabolic pathways. Our results should be crucial for further analyses of changes in different physiological and pathophysiological conditions in donkeys.

Once inflation occurs, it will have an important impact on the company's financial management. Under the circumstances of inflation, it will face low wages and rising prices, which will also affect the company's financial management. This article focuses on the analysis and discussion of the impact of inflation on corporate finance and countermeasures. First, the concept and specific situation of inflation are introduced, then the impact of inflation on the company's financial management is analyzed. Finally,effective countermeasures are put forward to do a good job in the company's financial management under inflation.

Cultural values have a wide influence on international business management and its related activities. In people's daily living environment, due to the different culture and education people receive, the growing environment is different, so it can be divided into different groups, resulting in the relationship between each different cultural groups more and more estranged. If there is no correct sense of management, it is difficult to have close communication, and even there will be barriers in communication. This article mainly analyzes the cross-cultural issues, expounds the cultural factors in international business management, enumerates the cultural differences in international business management, and makes an in-depth analysis of the role of cultural values in international business management and related activities. The purpose is to strengthen the management awareness of relevant managers in cross-cultural management.

Zebrafish were placed in the upper layer of aquariums to investigate the impacts of anatase and rutile nano-TiO2 on perfluorooctanesulfonate (PFOS) bioaccumulation in zebrafish. Both variations of particle hydrodynamic size and concentration in water column suggest that anatase was better dispersed than rutile. PFOS could be significantly adsorbed on nano-TiO2 to form TiO2-PFOS complexes, leading to reduced concentration of PFOS in upper layer. Due to enhanced exposure to PFOS by ingestion and adhesion of TiO2-PFOS complexes, the whole-body PFOS concentration in zebrafish was enhanced by 59.0% (95% CI: 55.9%, 61.9%) and 25.4% (95% CI: 24.8%, 25.6%) in the presence of anatase and rutile nano-TiO2 after equilibrium compared with the control with PFOS alone. The bioaccumulation of PFOS was much more promoted by anatase, which was attributed by greater adsorption capacity of PFOS to anatase, slower migration of their complex in water column, and slower elimination rate of anatase from fish.

This study aimed to explore the effect of DT-13 (25(R,S)-ruscogenin- 1-O- [β-d-glucopyranosyl- (1→2)][β-d-xylopyranosyl-(1→3)]-β -d- fucopyranoside) on tumor necrosis factor (TNF)-α-induced vascular inflammation and the potential molecular mechanisms. In vitro, DT-13 suppressed TNF-α-induced adhesion and migration of human umbilical vein endothelial cells (HUVECs) by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). DT-13 markedly suppressed NF-кB p65 phosphorylation, and when NF-кB p65 was over-expressed, the inhibitory effect of DT-13 on adhesion molecular decreased. DT-13 also suppressed TNF-α induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-κB binding sites. Furthermore, DT-13 markedly suppressed p38 phosphorylation and Src degradation induced by TNF-α, whereas had no significant effect on ERK and JNK activation. In vivo, DT-13 at 4 mg/kg prevented vascular inflammation and the expression of adhesion molecules induced by TNF-α in mice. These findings suggest that DT-13 abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-кB, p38MAPK, Src signaling pathways, and NF-κB binding site is at least one of the targets of DT-13. This study provides novel information regarding the mechanism by which DT-13 exerts its effects on vascular inflammation, which is important for the onset and progression of various diseases.

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40 mg/kg and 80 mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH.

YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathwaysin vivoandin vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.

Biotransformation of PFOS-precursors (PreFOS) may contribute significantly to the level of perfluorooctanesulfonate (PFOS) in the environment. Perfluorooctane sulfonamide (PFOSA) is one of the major intermediates of higher molecular weight PreFOS. Its further degradation to PFOS could be isomer specific and thereby explain unexpected high percentages of branched (Br-) PFOS isomers observed in wildlife. In this study, isomeric degradation of PFOSA was concomitantly investigated by in vivo and in vitro tests using common carp as an animal model. In the in vivo tests branched isomers of PFOSA and PFOS were eliminated faster than the corresponding linear (n-) isomers, leading to enrichment of n-PFOSA in the fish. In contrast, Br-PFOS was enriched in the fish, suggesting that Br-PFOSA isomers were preferentially metabolized to Br-PFOS over n-PFOSA. This was confirmed by the in vitro test. The exception was 1m-PFOSA, which could be the most difficult to be metabolized due to its α-branched structure, resulting in the deficiency of 1m-PFOS in the fish. The in vitro tests indicated that the metabolism mainly took place in the fish liver instead of its kidney, and it was mainly a Phase I reaction. The results may help to explain the special PFOS isomer profile observed in wildlife.

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

Ophiopogonin-D is one of steroidal saponins isolated from the root of the Chinese medicinal plant Ophiopogon japonicas. It has been claimed to possess anti-inflammatory and anti-oxidant properties. The present study was the first to examine the anti-tumor metastasis properties of ophiopogonin-D. An MTT assay showed that ophiopogonin-D inhibited the proliferation of MDA-MB-435 melanoma cells, and decreased invasion was demonstrated using a Transwell invasion assay. Furthermore, adhesion of MDA-MB-435 cells to human umbilical vascular endothelial cells and to fibronectin was inhibited by ophiopogonin-D. Gelatin zymography and western blot analysis showed that ophiopogonin-D inhibited the expression and secretion of matrix metalloproteinase-9 (MMP-9), but not that of MMP-2. Inhibition of phosphorylation of p38 by ophiopogonin-D indicated its inhibition of the mitogen-activated protein kinase pathway. Overall, the results suggested that ophiopogonin-D may be considered as a candidate drug for treating or preventing tumor metastasis.