Search

Nickel-vanadium (NiV)-layered double hydroxide (LDH) was fabricated into a novel saturable absorber (SA) by the liquid phase exfoliation method and utilized as the laser modulator for the first time, to our best knowledge. We investigated a passive Q -switched Tm:YAG ceramic laser at 2 µm with the NiV-LDH SA. Under an absorbed pump power of 7.2 W, the shortest pulse width of 398 ns was obtained with an average output power of 263 mW and a pulse repetition frequency of 101.8 kHz, corresponding to a single pulse energy at 2.30 µJ. The results indicate that the NiV-LDH SA has great research potential in the field of laser modulation.

A rich of 3,4-seco-lupane triterpenoids including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA) and chiisanogenin (CSG) were isolated from the ethanol extract of the leaves of Acanthopanax sessiliflorus. On the basis of previous studies, this article focused on four important components of 3,4-seco-lupane triterpenoids in Acanthopanax sessiliflorus leaves and explored their protective effects against aconitine-induced cardiomyocyte injury and their molecular mechanisms. The results showed that pretreatment with 3,4-seco-lupane triterpenoids could effectively increase cell viability, reduce CK-MB and LDH activities, reduce ROS production, maintain calcium concentration balance, and inhibit apoptosis, with divaroside having the best effect. In addition, Western blot results showed that divaroside down-regulated Cleaved caspase-3 and Bax and up-regulated Bcl-2 expression through activating the PI3 K/AKT pathway. However, the LY294002 inhibitor reversed this situation. This suggests that 3,4-seco-lupane triterpenoids may be a new hotspot for potential myocardial protective drugs research., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Uterine rupture in pregnancy is associated with severe maternal and fetal complications. Although it is a rare event, uterine rupture has been associated with certain risk factors. Glucocorticoids are known to weaken skeletal muscles; however, there have been no studies on the effects of chronic steroid use on the uterine myometrium., Case: We present the case of a 40-year-old multigravid woman who experienced a posterior uterine wall rupture on an unscarred uterus. She was on chronic glucocorticoids for the treatment of psoriatic arthritis. We hypothesize that the catabolic effects of glucocorticoids on skeletal muscles also weakened the uterine myometrium, leading to a higher risk of uterine rupture., Conclusion: Uterine rupture may be associated with chronic use of corticosteroids. Identifying the different risk factors for uterine rupture can lead to more prompt diagnosis and management of uterine rupture, resulting in better maternal and fetal outcomes., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: 5-O-methylvisammioside (MeV), also known as 4'-O-β-D-glucosyl-5-O-methylvisamminol, is a conventional marker compound for quality control of roots of Saposhnikovia diviaricata (Radix Saposhnikoviae), which exhibits anti-inflammatory and neuroprotective activities., Purpose: According to the activity of MeV, we speculated that MeV may have antidepressant effect on LPS induced depression, and further explored its mechanism., Study Design: First, to explore the effect and mechanism of MeV on LPS-induced depression in mice, and then to further explore the effect and mechanism of MeV on LPS-activated BV-2 microglia., Methods: By the OFT, EPM, TST and FST behavioral tests, to explore the effect of MeV pretreatment on the behavior of LPS-induced depression mice. ELISA and Griess method were used to detect the changes of the serum TNF-α and IL-6 levels, the hippocampus SOD and MDA levels, and the NO, SOD, MDA, TNF-α and IL-6 levels in the culture medium of LPS-stimulated BV-2 microglia. Western blot was used to analyze the protein expression in the Nf-κB/IκB-α and BDNF/TrkB pathway in the hippocampus of mice and BV-2 microglia., Results: MeV (4 mg/kg, i.p.) pretreatment significantly improves the activity and exploration ability of LPS-induced depression mice, and reduces the immobility time. MeV inhibited the production of pro-inflammatory cytokines in the serum of mice induced by LPS, such as IL-6 and TNF-α. MeV also increased the levels of SOD and reduces the expression of MDA in the hippocampus, thus promoting the alleviation of depressive symptoms in mice. Western blotting analysis showed that the antidepressant activity of MeV was related to the decrease of Nf-κB nuclear transport, the inhibition of IκB-α phosphorylation, and the increase of BDNF and TrkB expression. MeV (40 μM) significantly reduced the contents of NO, MDA, TNF-α and IL-6 in the culture medium of LPS-stimulated BV-2 microglia, and increased the content of SOD., Conclusion: MeV can regulate the neurotrophic factors in the mouse brain, reduce the content of inflammatory factors by the Nf-κB/IκB-α pathway, improve oxidative stress, and inhibit the excessive activation of LPS-stimulated BV -2 microglia. It effectively reversed the depression-like behAavior induced by LPS in mice., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Laser welding-brazing was performed to join Ti and Al together. The dual-spot laser beam mode was selected as the heat source in this study. Ti-6Al-4V and 6061-T6 Al alloys were selected as the experimental materials. Al-12Si welding wire was selected as the filler material. The effect of groove shape on the weld appearance, microstructure, temperature field, and mechanical performance of Ti/Al welded-brazed butt joints was investigated. The interfacial intermetallic compound (IMC) layer at the Ti/Weld brazing interface was inhomogeneous in joints with I-shaped and Y-shaped grooves. In Ti/Al joints with V-shaped grooves, the homogeneity of temperature field and IMC layer was improved, and the maximum thickness difference of IMC layer was only 0.20 μm. Nano-sized granular Ti 7 Al 5 Si 12 , Ti 5 Si 3 , and Ti(Al,Si) 3 constituted the IMCs. The tensile strength of Ti/Al joints with V-shaped grooves was the highest at 187 MPa. The fracture mode transformed from brittle fractures located in the IMC layer to ductile fractures located in the Al base metal, which could be attributed to the improvement of the IMC layer at the brazing interface.

We investigated the mechanism of action of panaxynol (PAL) extract from the root of Saposhnikovia diviaricata (Turcz.) Schischk for treating acute liver injury caused by lipopolysaccharide (LPS) and D-galactosamine (D-Gal N) in mice. A mouse model of acute liver failure induced by LPS/D-Gal N was established. Mice were divided randomly into three equal groups: control group, LPS/D-Gal N group and PAL group. After seven days of continuous PAL administration, all animals except controls were injected with 50 μg/kg LPS and 800 mg/kg D-Gal N; blood and liver samples were collected after 8 h. Compared to the LPS/D-Gal N group, the levels of catalase, glutathione and superoxide dismutase were increased in the liver of the PAL group. The inflammatory response index indicated that PAL attenuated LPS/D Gal N-induced liver pathological injury and decreased levels of hepatic malondialdehyde, serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α, and interleukins 1β and 6. PAL also inhibited LPS/D-Gal N induced nuclear factor-kappa B (Nf-κB), inhibitor kappa B-α (IκB-α) activation, and up-regulated Nrf2 and heme oxygenase-1 (HO-1) expression. PAL can prevent LPS/D-Gal N induced acute liver injury by activating Nrf2/HO-1 to stimulate antioxidant defense and inhibit the IkB-α/NF-κB signaling pathway.

Snake venom metalloproteinases (SVMPs) are an important component in viperid and crotalid venoms, and these SVMPs play important and versatile roles in the pathogenesis of snakebite envenoming. The SVMPs from elapid venoms are not well elucidated compared with those from viperid and crotalid venoms. Atrase B is a nonhemorrhagic P-III SVMP purified from the Naja atra venom, which possesses a weak fibrinogenolytic activity. In this paper, the activity and mechanism of atrase B against platelet aggregation and blood coagulation were investigated. The in vitro assay showed that atrase B remarkably inhibited ristocetin- and thrombin-induced platelet aggregation by cleavage of the platelet membrane glycoprotein Ib, and the coagulation of normal human plasma, which may be caused by inhibiting coagulation factor VIII predominantly. When atrase B was intravenously injected into rats at doses of 0.05 and 0.30 mg/kg, the activated partial thromboplastin and the thrombin times were significantly prolonged in a dose-dependent manner. Similarly, the fibrinogen level decreased, but only a high dose of atrase B showed remarkable activity against platelet aggregation. Results suggested that anticoagulation was a more important function of atrase B compared with its activity against platelet aggregation. These results indicated that atrase B may play an important role in the anticoagulant properties of Naja atra venom. In addition, atrase B may be a potent anticoagulant agent because its effectiveness in vivo against platelet aggregation and blood coagulation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Lactate accumulation in the brain is caused by the anaerobic metabolism induced by ischemic damages, which always accompanies intracerebral hemorrhages (ICH). Our former findings showed that microglia's movement was always directly toward hemorrhagic center with the highest lactate concentration, and penumbra area has the largest density of compactly arrayed microglia. However, the relationship between microglia and lactate concentration has not been well documented., Methods: Cerebral hemorrhage model was successfully achieved by injecting collagenase VII (causing stabile localized bleeding) in CPu (striatum) of SD rats. Emodin was used as a potential therapeutic for ICH. The function of the lactate was examined with in vitro culture studies. Then, the effect of lactate on the proliferation, cell survival, migration, and phagocytosis property of microglia was investigated by in vitro culture studies., Results: Lactate accumulation was observed with in vivo MRS method, and its concentration was monitored during the recovery of ICH and treatment of emodin. Lactate concentration significantly increased in the core and penumbra regions of hemorrhagic foci, and it decreased after the treatment of emodin. The in vitro culture study was verified that lactate was beneficial for the proliferation, cell survival, migration, and phagocytosis property of the microglia., Conclusion: Results from in vitro verification study, investigations from the recovery of ICH, and treatment of emodin verify that lactate plays an important role during the recovery of ICH. This could provide a novel therapeutic approach for ICH., (© 2020 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

CO 2 reforming of methane (CRM) can effectively convert two greenhouse gases (CO 2 and CH 4 ) into syngas (CO + H 2 ). This process can achieve the efficient resource utilization of CO 2 and CH 4 and reduce greenhouse gases. Therefore, CRM has been considered as a significantly promising route to solve environmental problems caused by greenhouse effect. Ni-based catalysts have been widely investigated in CRM reactions due to their various advantages, such as high catalytic activity, low price, and abundant reserves. However, Ni-based catalysts usually suffer from rapid deactivation because of thermal sintering of metallic Ni active sites and surface coke deposition, which restricted the industrialization of Ni-based catalysts toward the CRM process. In order to address these challenges, scientists all around the world have devoted great efforts to investigating various influencing factors, such as the option of appropriate supports and promoters and the construction of strong metal-support interaction. Therefore, we carefully summarized recent development in the design and preparation of Ni-based catalysts with advanced catalytic activity and enhanced anti-coke performance toward CRM reactions in this review. Specifically, recent progresses of Ni-based catalysts with different supports, additives, preparation methods, and so on, have been summarized in detail. Furthermore, recent development of reaction mechanism studies over Ni-based catalysts was also covered by this review. Finally, it is prospected that the Ni-based catalyst supported by an ordered mesoporous framework and the combined reforming of methane will become the future development trend., (Copyright © 2020 Wu, Xu, Chen, Lv, Wen, Cui, Wu, Yang, Miao and Hu.)

Objectives: Lymph node metastasis (LNM) is an important determinant of prognosis in patients with cervical cancer. Members of the angiopoietin family have been demonstrated to regulate tumor-associated angiogenesis and lymphangiogenesis. This study aimed to investigate the expression levels of angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) in clinically early stage of cervical cancer along with their correlations with LNM., Methods: In total, 124 human cervical cancer cases classified into stage IA-IIB in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria were included. ANG1 and ANG2 expression levels in the tumor sections were assessed by immunohistochemistry (IHC). Univariate and multivariate logistic regression models, including age at diagnosis, FIGO stage, tumor size, pathological type, histological grading, depth of stromal invasion, lymph-vascular space invasion (LVSI) and the expression status of ANG1 and ANG2, were used to evaluate the odds ratios (ORs) for LNM., Results: ANG1 and ANG2 were positively expressed in 75 (60.5%) and 89 (71.8%) cervical cancers respectively, with predominant staining in the cytoplasm. ANG1 expression was significantly decreased in tumors with LNM, while no correlation was observed between ANG2 expression and LNM. More importantly, the multivariate logistic regression analysis demonstrated that high ANG1 expression was an independent protective factor of LNM (OR 0.107, 95% confidential interval [CI] 0.020~0.567), while LVSI was an independent risk factor of LNM (OR 34.313, 95% CI 5.914~199.092)., Conclusion: ANG1 is associated with a significantly decreased risk of LNM in early stage cervical cancer. The predictive value and role of ANG1 in LNM needs to be further investigated in future studies.

OBJECTIVE. This study aims to assess correlations of the time from symptom onset to diagnosis and treatment with the time to disease resolution and CT scores as based on findings from sequential chest CT examinations. MATERIALS AND METHODS. Thirty patients with coronavirus disease (COVID-19) confirmed by reverse transcription-polymerase chain reaction analysis underwent chest CT examinations. Five patients who did not have positive CT findings or who had not yet fulfilled criteria for discharge from the hospital were excluded. CT scores were determined according to CT findings and lung involvement. The time from symptom onset to diagnosis and treatment was recorded for each patient, and on the basis of this information, patients with COVID-19 were divided into group 1 (patients for whom this interval was ≤ 3 days) and group 2 (those for whom this interval was > 3 days). The CT scores for each group were fitted using a Lorentzian line-shape curve to show the variation tendency during treatment. The differences in age, sex, and last CT scores determined before discharge between the two groups were analyzed, and correlations of the time from symptom onset to diagnosis and treatment with the time to disease resolution as well as with the highest CT score also underwent statistical analysis. RESULTS. A total of 25 subjects were enrolled in the study. The fitted tendency curves for group 1 and group 2 were significantly different, with peak points showing that the estimated highest CT score was 10 and 16 for each group, respectively, and the time to disease resolution was 6 and 13 days, respectively. The Mann-Whitney test showed that the last CT scores were lower for group 1 than for group 2 ( p = 0.025), although the chi-square test found no difference in age and sex between the groups. The time from symptom onset to diagnosis and treatment had a positive correlation with the time to disease resolution ( r = 0.93; p = 0.000) as well as with the highest CT score ( r = 0.83; p = 0.006). CONCLUSION. Timely diagnosis and treatment are key to providing a better prognosis for patients with COVID-19.

The utility of prognostic and predictive immunohistochemistry biomarkers in the context of cancer is plagued by inconsistent interpretation of results which can lead to poor rates of adoption or inappropriate use of novel therapeutic strategies. To monitor immunohistochemistry assay performance, a new on-slide control motif, Immunohistochemistry Critical Assay Performance Controls (ICAPC) was developed. We hypothesized that the use of these controls by the diagnosing pathologist to interpret BRAFV600E would result in reduced interobserver and intraobserver interpretation errors. A cross-sectional, sequentially obtained sample of surgical pathology cases stained for BRAFV600E was assembled from a single hospital in Vancouver, British Columbia. Half of the cases had normal on-slide controls and the remainder with ICAPC. Results from 6 independent and blinded readers were compared with each other and to the gold-standard pathologic diagnosis with the goal of demonstrating superior interrater agreement with ICAPC relative to standard on-slide controls. Cohen's κ was used to compute pair-wise reader agreements, whereas Fleiss' κ was used to compare to the gold standard. The implementation of ICAPC resulted in statistically significant improvements in the interobserver agreement of BRAF mutation status ascertained by BRAFV600E immunohistochemistry. Half of the readers demonstrated significant improvements in agreement with the gold-standard diagnosis with the addition of ICAPC. Across all readers, the mean increase in κ was 0.14 with a 95% confidence interval of 0.01-0.28 (P=0.04). This study demonstrates that the addition of ICAPC serves to significantly reduce interobserver variability in the assessment of BRAFV600E immunohistochemistry. As such, we recommend that this approach should be used as part of a comprehensive quality management strategy in the setting of histopathology.

A new minor 3,4-seco-lupane triterpenene glycosyl ester, named sessiloside-A1 ( 1 ), along with three known 3,4-seco-lupane triterpenenes were isolated from the which alcohol extract of the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y. Hu by silica gel column chromatography, and their structures were determined by spectroscopic methods (UV, IR, NMR and HRMS). Compound 1 was elucidated to be β- D-glucopyranosyl ester of chiisanogenin. At the same time, a new efficient two-step enzymatic hydrolysis method was established to transform chiisanoside (2) → divaroside (3) → 1 .

Generation of tumor-infiltrating lymphocytes begins when tumor antigens reach the lymph node (LN) to stimulate T cells, yet we know little of how tumor material is disseminated among the large variety of antigen-presenting dendritic cell (DC) subsets in the LN. Here, we demonstrate that tumor proteins are carried to the LN within discrete vesicles inside DCs and are then transferred among DC subsets. A synapse is formed between interacting DCs and vesicle transfer takes place in the absence of free exosomes. DCs -containing vesicles can uniquely activate T cells, whereas DCs lacking them do not. Understanding this restricted sharing of tumor identity provides substantial room for engineering better anti-tumor immunity., Competing Interests: Declaration of Interests Authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

With the development and prosperity of the global economy, the emission of carbon dioxide (CO 2 ) has become an increasing concern. Its greenhouse effect will cause serious environmental problems, such as the global warming and climate change. Therefore, the worldwide scientists have devoted great efforts to control CO 2 emissions through various strategies, such as capture, resource utilization, sequestration, etc. Among these, the catalytic conversion of CO 2 to methane is considered as one of the most efficient routes for resource utilization of CO 2 owing to the mild reaction conditions and simple reaction device. Pioneer thermodynamic studies have revealed that low reaction temperature is beneficial to the high catalytic activity and CH 4 selectivity. However, the low temperature will be adverse to the enhancement of the reaction rate due to kinetic barrier for the activation of CO 2 . Therefore, the invention of highly efficient catalysts with promising low temperature activities toward CO 2 methanation reaction is the key solution. The Ni based catalysts have been widely investigated as the catalysts toward CO 2 methanation due to their low cost and excellent catalytic performances. However, the Ni based catalysts usually perform poor low-temperature activities and stabilities. Therefore, the development of highly efficient Ni based catalysts with excellent low-temperature catalytic performances has become the research focus as well as challenge in this field. Therefore, we summarized the recent research progresses of constructing highly efficient Ni based catalysts toward CO 2 methanation in this review. Specifically, the strategies on how to enhance the catalytic performances of the Ni based catalysts have been carefully reviewed, which include various influencing factors, such as catalytic supports, catalytic auxiliaries and dopants, the fabrication methods, reaction conditions, etc. Finally, the future development trend of the Ni based catalysts is also prospected, which will be helpful to the design and fabrication of the Ni catalysts with high efficiency toward CO 2 methanation process., (Copyright © 2020 Lv, Xu, Chen, Cui, Wen, Li, Wu, Yang, Miao, Hu and Shou.)

Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice., Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg 1 , Re, Rb 1 , Rc, Rb 2 , Rb 3 , Rd, Rk 3 , Rh 4 , 20 (S)-Rg 3 , 20 (R)-Rg 3 , Rk 1 , Rg 5 , salidroside, and so on., Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G 2 /M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious., Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components., (© 2019 The Korean Society of Ginseng, Published by Elsevier Korea LLC.)

The present study explored the antidepressant-like activity of α-mangostin (α-MG) and the possible mechanism in this process in the tail suspension test (TST) in mice. The results revealed that α-MG (5 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D 2 receptor antagonist), bicuculline (a competitive GABA antagonist), p-chlorophenylalanine (an inhibitor of 5-HT synthesis). Meanwhile, α-MG also effectively increased the brain DA, 5-HT and GABA levels in mice exposed to TST, indicating that the antidepressant-like effect of α-MG might be mediated by the GABAergic, serotonergic and dopaminergic systems.[Formula: see text].

Panaxynol (PAL, also called falcarinol) is widely found in plants of the Umbelliferae family, among which carrots are rich in PAL, so it is proved to be edible. PAL has neuroprotective effects and other pharmacological activities. This study aimed to explore the effects and mechanisms of action of PAL on chronic unpredictable mild stress (CUMS)-induced anxiety and depression in mice. The effects of PAL on behavioral activities in mice were first assessed by a CUMS-induced depression model. The secretion levels of monoamine neurotransmitters and hypothalamic-pituitary-adrenal (HPA) axis-related hormones were measured by ELISA. Western blotting was used to analyze the expression of glucocorticoid receptor (GR), glutamate receptor 1 (GluR1) and synapse-associated protein in the hippocampus. The behavioral experiment results showed that PAL can improve exploratory behavior and activities in mice. Meanwhile, PAL can significantly activate the release of 5-HT/5-HIAA and DA/HVA in the hippocampus. It inhibits the expression of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and corticotrophin-releasing hormone (CRH) in serum and the hypothalamus. The contents of GR, glutamate receptor 1 (GluR1), postsynaptic density-95 (PSD95) and synapsin I protein in the hippocampus significantly increased. Studies have found that PAL can inhibit the hyperfunction of the HPA axis, which may be achieved by regulating HPA axis hormones and GR. Meanwhile, PAL promotes the release of 5-HT and DA in the hippocampus and improves synaptic plasticity in the hippocampus, allowing neurotransmitters to function more effectively. Therefore, PAL may improve anxiety and depression-like effects in mice through the abovementioned effects.

Sialylation, a post-translational modification that impacts the structure, activity, and longevity of glycoproteins has been thought to be controlled primarily by the expression of sialyltransferases (STs). In this report we explore the complementary impact of metabolic flux on sialylation using a glycoengineering approach. Specifically, we treated three human breast cell lines (MCF10A, T-47D, and MDA-MB-231) with 1,3,4-O-Bu 3 ManNAc, a "high flux" metabolic precursor for the sialic acid biosynthetic pathway. We then analyzed N-glycan sialylation using solid phase extraction of glycopeptides (SPEG) mass spectrometry-based proteomics under conditions that selectively captured sialic acid-containing glycopeptides, referred to as "sialoglycosites." Gene ontology (GO) analysis showed that flux-based changes to sialylation were broadly distributed across classes of proteins in 1,3,4-O-Bu 3 ManNAc-treated cells. Only three categories of proteins, however, were "highly responsive" to flux (defined as two or more sialylation changes of 10-fold or greater). Two of these categories were cell signaling and cell adhesion, which reflect well-known roles of sialic acid in oncogenesis. A third category-protein folding chaperones-was unexpected because little precedent exists for the role of glycosylation in the activity of these proteins. The highly flux-responsive proteins were all linked to cancer but sometimes as tumor suppressors, other times as proto-oncogenes, or sometimes both depending on sialylation status. A notable aspect of our analysis of metabolically glycoengineered breast cells was decreased sialylation of a subset of glycosites, which was unexpected because of the increased intracellular levels of sialometabolite "building blocks" in the 1,3,4-O-Bu 3 ManNAc-treated cells. Sites of decreased sialylation were minor in the MCF10A (<25% of all glycosites) and T-47D (<15%) cells but dominated in the MDA-MB-231 line (~60%) suggesting that excess sialic acid could be detrimental in advanced cancer and cancer cells can evolve mechanisms to guard against hypersialylation. In summary, flux-driven changes to sialylation offer an intriguing and novel mechanism to switch between context-dependent pro- or anti-cancer activities of the several oncoproteins identified in this study. These findings illustrate how metabolic glycoengineering can uncover novel roles of sialic acid in oncogenesis., (Copyright © 2020 Saeui, Cho, Dharmarha, Nairn, Galizzi, Shah, Gowda, Park, Austin, Clarke, Cai, Buettner, Ariss, Moremen, Zhang and Yarema.)

Research Question: Does breast cancer spread and aggressiveness affect fertility-preservation results?, Design: Retrospective cohort study of women with breast cancer undergoing fertility-preservation treatment., Inclusion Criteria: age 18-38 years and use of gonadotrophin releasing hormone antagonist protocol; exclusion criteria: recurrent cancer, previous oncological treatment, previous ovarian surgery and known ovarian pathology. Stimulation cycle outcomes of women with low-stage breast cancer were compared with those with high-stage disease. Patients with low-grade (G 1-2 ) were compared with those with high-grade (G 3 ) malignancies., Primary Outcome: total number of mature oocytes; secondary outcomes: oestradiol level and number of follicles wider than 14 mm on the day of trigger, number of retrieved oocytes and cryopreserved embryos., Results: The final analysis included 155 patients. Patients with high-grade tumours (n = 80; age 32 years [28-35]) had significantly lower number of mature oocytes compared with patients with low-grade cancer (n = 75; age 32 years [28-35]; seven mature oocytes [4-10] versus 13 mature oocytes [7-17]; P = 0.0002). The number of cryopreserved embryos was also lower in the high-grade group (three [2-5] versus five [3-9]; P = 0.02). Stage-based analysis revealed a similar number of mature oocytes in high-stage (n = 73; age 32 years [28-35]) compared with low-stage group (n = 82; age 33 years [28-35]; eight mature oocytes [4-13] versus nine mature oocytes [7-15]; P = 0.06)., Conclusions: High-grade breast cancer has a negative effect on total number of mature oocytes and cryopreserved embryos., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Dysfunction of energy metabolism exerts a central role in triggering neuron death following cerebral ischemia. Neuronal energy metabolism is highly dependent on glucose. O-GlcNAcylation, a post-translational modification, is a novel pro-survival pathway that modulates glucose homeostasis in ischemic stroke. Here, we explored whether activation O-GlcNAcylation and maintaining energy homeostasis mediated the neuroprotective effect of 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside, a synthetic salidroside analog (named SalA-4 g) which was previously developed in our laboratory. For in vivo analyses, SalA-4 g improved the outcome after transient middle cerebral artery occlusion (MCAO). 18 F-FDG PET/MRI indicated that SalA-4 g accelerated the recovery of energy metabolism in the ipsilateral hippocampus in MCAO rats. In vitro analyses showed that glucose uptake was markedly increased, and O-GlcNAcylation was also activated by SalA-4 g in hippocampal neurons under both normal and oxygen glucose deprivation (OGD) conditions. Moreover, SalA-4 g exerted obvious neuroprotective effects in hippocampal neurons against moderate OGD injury. Our study indicates that boosting a pro-survival pathway-GlcNAcylation-and regulating energy homeostasis are important biochemical mechanisms responsible for SalA-4 g neuroprotection.

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk 3 (Rk 3 ) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk 3 on cyclophosphamide-induced myelosuppression., Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting., Results: Both Re and Rk 3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G 0 /G 1 phase cells, and increase the proliferation index. Finally, Re and Rk 3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3., Conclusion: Re and Rk 3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk 3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk 3 on myelosuppression., (© 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC.)

Objective: To study the changes of ginsenoside content in different proportion of Panax ginseng-Angelica sinensis (GA) co-decoction, and to explore the amelioration of hematopoietic function in mice after combined use of the two drugs. The active ingredient profiles in P. ginseng single decoction and co-decoction of GA were determined by high performance liquid chromatography (HPLC). The experimental pharmacology method was used to explore the effect of GA co-decoction on the hematopoietic function of chemotherapy mice., Results: The active ingredient profiles of the co-decoction of GA significantly changed compared with those of the single decoction. Compared with GA1:0 (single decoction of Panax ginseng), the routine ginsenosides of all proportions of GA decreased significantly, but the proportion of rare ginsenosides increased significantly. The changes of contents of rare ginsenosides of GA were basically consistent with the trends of effects on the myelosuppression induced by CY. Compared with the model group, GA significantly increased the number of bone marrow nucleated cells, thymus index, peripheral blood leukocytes and platelets, and significantly reduced the spleen index. Moreover, GA could promote G1 phase bone marrow cells to enter the cell cycle, increase the proportion of S phase cells and G2/M phase cells, and increase the cell proliferation index., Conclusion: GA can ameliorate the hematopoietic function of mice after chemotherapy, and GA2:3, GA3:2 were the best, which may be due to the changes of the pharmacodynamic material basis of GA after compatibility. All these results implied that GA may be an ideal drug and food supplement for the treatment of toxic and side effects of chemotherapeutic drugs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The sugarcane smut fungus Sporisorium scitamineum is bipolar and produces sporidia of two different mating types. During infection, haploid cells of opposite mating types can fuse to form dikaryotic hyphae that can colonize plant tissue. Mating and filamentation are therefore essential for S. scitamineum pathogenesis. In this study, we obtained one T-DNA insertion mutant disrupted in the gene encoding the pheromone response factor (Prf1), hereinafter named SsPRF1 , of S. scitamineum , via Agrobacterium tumefaciens -mediated transformation (ATMT) mutagenesis. Targeted deletion of SsPRF1 resulted in mutants with phenotypes similar to the T-DNA insertion mutant, including failure to mate with a compatible wild-type partner strain and being non-pathogenic on its host sugarcane. qRT-PCR analyses showed that SsPRF1 was essential for the transcription of pheromone-responsive mating type genes of the a1 locus. These results show that SsPRF1 is involved in mating and pathogenicity and plays a key role in pheromone signaling and filamentous growth in S. scitamineum .

The use of immunohistochemistry (IHC) as a companion diagnostic is an increasingly important part of the case workup by pathologists and is often central to clinical decision making. New predictive molecular markers are constantly sought for to improve treatment stratification parallel to drug development. Unfortunately, official biomarker guidelines lag behind, and pathologists are often left hesitating when medical oncologists request off-labelled biomarker testing. We performed a literature review of five commonly requested off-label IHC predictive biomarkers in gastrointestinal tract (GIT) malignancies: HER2, mismatch repair (MMR), PD-L1, BRAF V600E and ROS1. We found that HER2 amplification is rare and poorly associated to IHC overexpression in extracolonic and extragastric GIT cancers; however in KRAS wild type colorectal cancers, which fail conventional treatment, HER2 IHC may be useful and should be considered. For MMR testing, more evidence is needed to recommend reflex testing in GIT cancers for treatment purposes. MMR testing should not be discouraged in patients considered for second line checkpoint inhibitor therapy. With the exception of gastric tumors, PD-L1 IHC is a weak predictor of checkpoint inhibitor response in the GIT and should be replaced by MMR in this context. BRAF inhibitors showed activity in BRAF V600E mutated cholangiocarcinomas and pancreatic carcinomas in non-first line settings. ROS1 translocation is extremely rare and poorly correlated to ROS1 IHC expression in the GIT; currently there is no role for ROS1 IHC testing in GIT cancers. Overall, the predictive biomarker literature has grown exponentially, and official guidelines need to be updated more regularly to support pathologists' testing decisions.

Objective: To explore whether Arctigenin-Valine ester (ARG-V) can treat myelosuppression caused by chemotherapy., Methods: The number of peripheral blood cells of the mice was measured by an automatic blood analyzer, and the hematopoietic progenitor colonies CFU-GM, CFU-E, BFU-E, and CFU-Meg were cultured in vitro. Hematopoietic progenitor colonies and BMNCs were counted under an inverted microscope. The expressions of cytokines GM-CSF, EPO and TPO were detected by ELISA. The cell cycle was measured by flow cytometry. The expressions of related proteins MEK and p-ERK were quantitated by western blots, and the thymus index and spleen index were quantitated., Results: After taking ARG-V, the peripheral blood cells of the mice gradually returned to normal, the number of nucleated cells in the bone marrow increased, the thymus index increased, the spleen index decreased, the number of hematopoietic progenitor cells increased, and the hematopoietic cytokines decreased. And ARG-V promoted the transformation of myelosuppression cells from G0/G1 to S and from S to G2/M. ARG-V could up-regulate the expression of MEK and p-ERK, and low dose ARG-V is not as effective in all aspects as high dose ARG-V., Conclusion: ARG-V can effectively alleviate the myelosuppression that caused by intraperitoneal injection of CTX in 100mg/kg, and ARG-V can promote the proliferation and differentiation of hematopoietic progenitor cells and improve immunity, and the effect of high-dose Arctigenin-Valine ester is more significant to some extent., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The carbon dioxide (CO₂) is notorious as the greenhouse gas, which could cause the global warming and climate change. Therefore, the reduction of the atmospheric CO₂ emissions from power plants and other industrial facilities has become as an increasingly urgent concern. In the recent years, CO₂ capture and storage technologies have received a worldwide attention. Adsorption is considered as one of the efficient options for CO₂ capture because of its cost advantage, low energy requirement and extensive applicability over a relatively wide range of temperature and pressure. The metal organic frameworks (MOFs) show widely potential application prospects in CO₂ capture and storage owing to their outstanding textural properties, such as the extraordinarily high specific surface area, tunable pore size, ultrahigh porosity (up to 90%), high crystallinity, adjustable internal surface properties, and controllable structure. Herein, the most important research progress of MOFs materials on the CO₂ capture and storage in recent years has been comprehensively reviewed. The extraordinary characteristics and CO₂ capture performance of Zeolitic Imidazolate Frameworks (ZIFs), Bio-metal organic frameworks (bio-MOFs), IL@MOFs and MOF-composite materials were highlighted. The promising strategies for improving the CO₂ adsorption properties of MOFs materials, especially the low-pressure adsorption performance under actual flue gas conditions, are also carefully summarized. Besides, CO₂ is considered as an abundant, nontoxic, nonflammable, and renewable C1 resource for the synthesis of useful chemicals and fuels. The potential routes for resource utilization of the captured CO₂ are briefly proposed.

The basidiomycetous fungus Sporisorium scitamineum causes a serious sugarcane smut disease in major sugarcane growing areas. Sexual mating is essential for infection to the host; however, its underlying molecular mechanism has not been fully studied. In this study, we identified a conserved farnesyltransferase (FTase) β subunit Ram1 in S. scitamineum . The ram1 Δ mutant displayed significantly reduced mating/filamentation, thus of weak pathogenicity to the host cane. The ram1 Δ mutant sporidia showed more tolerant toward cell wall stressor Congo red compared to that of the wild-type. Transcriptional profiling showed that Congo red treatment resulted in notable up-regulation of the core genes involving in cell wall integrity pathway in ram1 Δ sporidia compared with that of WT, indicating that Ram1 may be involved in cell wall integrity regulation. In yeast the heterodimeric FTase is responsible for post-translational modification of Ras (small G protein) and a-factor (pheromone). We also identified and characterized two conserved Ras proteins, Ras1 and Ras2, respectively, and a MAT-1 pheromone precursor Mfa1. The ras1 Δ, ras2 Δ and mfa1 Δ mutants all displayed reduced mating/filamentation similar as the ram1 Δ mutant. However, both ras1 Δ and ras2 Δ mutants were hypersensitive to Congo red while the mfa1 Δ mutant was the same as wild-type. Overall our study displayed that RAM1 plays an essential role in S. scitamineum mating/filamentation, pathogenicity, and cell wall stability.

Major depression disorder, also known as depression, with a significant and persistent low mood as the main clinical features, is the main type of mood disorders. L-menthol (LM), the main active ingredient of mint, has been considered as safe and healthy natural ingredient by the Food and Drug Administration in the USA. In this study, LM (40 mg/kg, i.g.) produced antidepressant-like effect in the forced swimming test (FST) in mice. The sub-effective dose (5 mg/kg, i.g.) of LM combined with the sub-effective dose of fluoxetine (5 mg/kg, i.p.) or reboxetine (2.5 mg/kg, i.p.) could significantly shorten the immobility time in the FST. Pretreatment with ondansetron (a highly selective 5-HT 3 receptor antagonist, 8 mg/kg, i.p.), bicuculline [a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.] and haloperidol (a non-selective D 2 receptor antagonist, 0.2 mg/kg, i.p.) significantly reversed the antidepressant-like effect of LM (40 mg/kg, i.g.). In contrast, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and N -methyl-d-aspartic acid (an agonist at the glutamate site, 75 mg/kg, i.p.) did not eliminate the antidepressant-like effect of LM. All of these above indicated that LM is able to induce an antidepressant-like effect mediated by the modification of 5-HTergic, GABAergic and DAergic systems in the FST. LM might be used as combination therapy in depressed patients and is a potential antidepressant., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

In this study, we aimed to investigate the effects of the combination of Panax ginseng and Ophiopogon japonicus (PG-OJ) herbs at different ratios on myelosuppression induced by chemotherapy. The myelosuppression model was established using an intraperitoneal injection of 100 mg kg-1 cyclophosphamide (CTX) in mice. The mice were administered the PG-OJ extract or Shengmaiyin (SMY) at different proportions (1 : 0, 1 : 1, 1 : 2, 2 : 1, 2 : 3, 3 : 2, and 0 : 1). The changes in the chemical composition caused by decocting the herbs together were analyzed by HPLC. The parameters i.e. the number of bone marrow nucleated cells and peripheral blood cells and the thymus and spleen indices were determined after administration. The results indicated that the co-decoction of PG and OJ, especially at the ratio of 2 : 3, was more conducive to the conversion of conventional ginsenosides (Rg1, Re, Rb1, Rg2, Rc, Rb2, Rb3 and Rd) to rare ginsenosides (Rg5, Rk3, S-Rg3, R-Rg3, Rk1 and Rh1) and the dissolution of ophiopogonin D. In addition, PG-OJ has an excellent synergistic effect on myelosuppression induced by CTX in mice. PG-OJ could significantly increase the numbers of the bone marrow nucleated cells and peripheral blood cells; moreover, it increased the thymus index and decreased the spleen index. The herb pair with a ratio of 2 : 3 showed the best therapeutic effect. By combining the results of the chemical composition changes and pharmacological activities, it can be concluded that rare ginsenosides and ophiopogonin D may be the main material basis of PG-OJ for the treatment of bone marrow suppression after chemotherapy.

The fungal pathogen Sporisorium scitamineum causes sugarcane smut disease. The formation and growth of dikaryotic hypha after sexual mating is critical for S. scitamineum pathogenicity, however regulation of S. scitimineum mating has not been studied in detail. We identified and characterized the core components of the conserved cAMP/PKA pathway in S. scitamineum by reverse genetics. Our results showed that cAMP/PKA signalling pathway is essential for proper mating and filamentation, and thus critical for S. scitamineum virulence. We further demonstrated that an elevated intracellular ROS (reactive oxygen species) level promotes S. scitamineum mating-filamentation, via transcriptional regulation of ROS catabolic enzymes, and is under regulation of the cAMP/PKA signalling pathway. Furthermore, we found that fungal cAMP/PKA signalling pathway is also involved in regulation of host ROS response. Overall, our work displayed a positive role of elevated intracellular ROS in fungal differentiation and virulence., (© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.)

TomoTherapy can provide highly accurate SABR deliveries, but currently it does not have any effective motion management techniques. Shallow breathing has been identified as one possible motion management solution on TomoTherapy, which has been made possible with the BreatheWell audiovisual biofeedback (AVB) device. Since both the shallow breathing technique and the clinical use of the BreatheWell device are novel, their implementation requires comprehensive verification and validation work. As the first stage of the validation, this paper investigates the impact of target motion on a TomoTherapy SABR delivery is assessed on both 3D CT and 4D CT using a 4D respiratory phantom. A dosimetric study on a 4D respiratory phantom was conducted, with the phantom's insert designed to move at four different amplitudes in the superior-inferior direction. SABR plans on 3D and 4D CT scans were created and measured. Critical plan statistics and measurement results were compared. It is found that for TomoTherapy SABR deliveries, by reducing the targets respiratory motion, target coverage, organ-at-risk (OAR) sparing, and delivery accuracy were improved.

Ginsenoside compound K (CK) is not a ginsenoside that naturally exists in Panax ginseng Meyer. However, CK is a major metabolite of ginsenoside Rb 1 , Rb 2 , or Rc in the intestine under the effects of bacteria. In this study, we first investigated the effects of CK on myelosuppression in mice induced by cyclophosphamide (CTX). The respective quantities of white blood cells, blood platelets, and bone marrow nucleated cells (BMNCs) were determined to be 8.54 ± 0.91 (10 9 /L), 850.90 ± 44.11 (10 9 /L), and 1.45 ± 0.22 (10 9 /L) in the CK-H group by detecting peripheral blood cells and BMNCs. CK-H and CK-L both increased the thymus index by up to 0.62 ± 0.06 (mg/g) and 0.52 ± 0.09 (mg/g), respectively, and significantly increased the yields of colony formation units-granulocyte monocyte and colony formation units-megakaryocytic. According to our study, CK could control apoptosis and promote cells to enter the normal cell cycle by the bcl-2/bax signaling pathway and MEK/ERK signaling pathway. Therefore, the BMNCs could proliferate and differentiate normally after entering the normal cell cycle. So the peripheral blood cells could show a trend of returning to normal. The recovery of peripheral blood cells resulting in the level of cytokines tended to normal. This process may be the mechanisms of CK on myelosuppression. This study provides a reference for ginseng in the treatment of myelosuppression.

In the past two decades, great progress has been made in the aspects of fabrication and application of ordered mesoporous metal oxides. Ordered mesoporous metal oxides have attracted more and more attention due to their large surface areas and pore volumes, unblocked pore structure, and good thermal stabilities. Compared with non-porous metal oxides, the most prominent feature is their ability to interact with molecules not only on their outer surface but also on the large internal surfaces of the material, providing more accessible active sites for the reactants. This review carefully describes the characteristics, classification and synthesis of ordered mesoporous metal oxides in detail. Besides, it also summarizes the catalytic application of ordered mesoporous metal oxides in the field of carbon dioxide conversion and resource utilization, which provides prospective viewpoints to reduce the emission of greenhouse gas and the inhibition of global warming. Although the scope of current review is mainly limited to the ordered mesoporous metal oxides and their application in the field of CO₂ catalytic conversion via heterogeneous catalysis processes, we believe that it will provide new insights and viewpoints to the further development of heterogeneous catalytic materials.

This study investigated the combination effects of the Acanthopanax senticosus - Ligustrum lucidum (AS-LL) herb pair on bone marrow suppression caused by chemotherapy. A bone marrow suppression model was established by intraperitoneal injection (i.p.) of cyclophosphamide (CTX, 100 mg/kg). The changes in chemical composition between the AS-LL decocted together and single were analyzed, and their effects on the bone marrow nucleated cells, peripheral blood, thymus and spleen indices, in vitro hematopoietic cell culture, ELISA and cell cycle were detected. The results showed that the contents of the main active components, such as salidroside, isofraxidin and specnuezhenide in the sample of AS-LL decocted together, increased significantly compared to singles. Moreover, AS-LL decocted together exhibited a significantly better therapeutic effect on myelosuppression induced by CTX than AS and LL alone. AS-LL decocted together significantly increased the number of bone marrow nucleated cells and displayed a good regulatory effect on peripheral blood (p < 0.01), while significantly increased the thymus index (p < 0.01) and decreased the spleen index (p < 0.01). AS-LL significantly promoted the formation of cell colonies (p < 0.05), the proliferation and differentiation of hematopoietic progenitor cells, and played a positive regulatory role in hematopoietic factors. AS-LL also reduced the proportion of G0/G1 cells, increased the ratio of S and G2/M cells, and increased the cell proliferation index (PI). All these results implied that AS-LL decocted together might be a promising food additives and therapeutic agent for myelosuppression induced by chemotherapy., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Drug-related hepatotoxicity has become a serious social issue nowadays. Acetaminophen (APAP) was widely used in clinical treatment, although commonly acknowledged that it is a general material that caused drug-related hepatotoxicity. In this study, triterpenoids (Trds) which are mainly composed of ursolic acid and oleanolic acid, were isolated and prepared from fruits of Sorbus pohuashanensis. Further, the effect of Trds against APAP-induced liver injury and the pharmacological mechanism were investigated. The results showed that Trds treatment significantly restrained the increase of serum aspartate transaminase (AST), alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) levels, as well as evidently reversed the decrease of hepatic superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) levels induced by APAP. There are further evidences provided by liver histopathology which demonstrated Trds treatment observably inhibited hepatic tissues necrosis, hemorrhage and infiltration of inflammatory cell induced by APAP. According to the results of western-blot and RT-PCR, the over-expressions of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2) were inhibited by Trds. Moreover, Trds also effectively restrained APAP-induced phosphorylation of mitogen-activated protein kinase (MAPK) family signals such as p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). These results demonstrated the liver-protection effects that Trds exhibited were related to its property of anti-oxidantion and anti-inflammation., (Copyright © 2018. Published by Elsevier Masson SAS.)

Silver nanoparticles (AgNPs) are increasingly utilized in a number of applications. This study was designed to investigate AgNPs induced cytotoxicity, oxidative stress and apoptosis in rat tracheal epithelial cells (RTE). The RTE cells were treated with 0, 100 μg/L and 10,000 μg/L of the AgNPs with diameters of 10 nm and 100 nm for 12 hr. The cell inhibition level, apoptosis ratio, reactive oxygen species (ROS), malondialdehyde (MDA) and metallothionein (MT) content were determined. The mRNA expression of cytoc, caspase 3, and caspase 9 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we also analyzed the cytoc, caspase 3, pro-caspase 3, caspase 9, and pro-caspase 9 protein expression by western blotting. Electric cell-substrate impedance sensing (ECIS) analysis showed that the growth and proliferation of RTE cells were significantly inhibited in a dose-dependent manner under AgNPs exposure. The cell dynamic changes induced by 10 nm AgNPs were more severe than that of the 100 nm AgNPs exposure group. The intracellular MT, ROS, and MDA content increased when the exposure concentration increased and size reduced, whereas Ca 2+ -ATPase activity and Na + /K + -ATPase activity changed inversely. The relative expression of protein of cytoc, caspase 3, and caspase 9 were upregulated significantly, which indicated that AgNPs induced apoptosis of RTE cells through the caspase-dependent mitochondrial pathway. Our results demonstrate that AgNPs caused obvious cytotoxicity, oxidative stress, and apoptosis in RTE cells, which promoted the releasing of cytochrome C and pro-apoptotic proteins into the cytoplasm to activate the caspase cascade and finally led to apoptosis.

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) that are functionally brighter; detect submicromolar to millimolar amounts of glutamate; and have blue, cyan, green, or yellow emission profiles. These variants could be imaged in vivo in cases where original iGluSnFR was too dim, resolved glutamate transients in dendritic spines and axonal boutons, and allowed imaging at kilohertz rates.

The purpose of this study was to investigate the hepatoprotective effect of α-mangostin (α-MG) on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced acute liver failure and discover its potential mechanisms in mice. The results showed that α-MG could attenuate LPS/D-GalN-induced liver pathological injury, and decrease the hepatic malondialdehyde (MDA) level, serum alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF-α), interleukin-1β and 6 (IL-1β, IL-6) levels and recovery hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) activities. The results also indicated that α-MG inhibited LPS/D-GalN-induced toll-like receptor 4 (TLR4) expression and NF-κB activation. In addition, α-MG up-regulated the expressions of Nrf2 and heme oxygenase-1 (HO-1). In conclusion, the results indicated that α-MG could protect against LPS/D-GalN-induced liver failure by activating Nrf2 to induce antioxidant defense and inhibiting TLR4 signaling pathway to induce anti-inflammatory effect., (Copyright © 2018. Published by Elsevier Masson SAS.)

In bacterial type 3 secretion, substrate proteins are actively transported from the bacterial cytoplasm into the host cell cytoplasm by a large membrane-embedded machinery called the injectisome. Injectisomes transport secretion substrates in response to specific environmental signals, but the molecular details by which the cytosolic secretion substrates are selected and transported through the type 3 secretion pathway remain unclear. Secretion activity and substrate selectivity are thought to be controlled by a sorting platform consisting of the proteins SctK, SctQ, SctL, and SctN, which together localize to the cytoplasmic side of membrane-embedded injectisomes. However, recent work revealed that sorting platform proteins additionally exhibit substantial cytosolic populations and that SctQ reversibly binds to and dissociates from the cytoplasmic side of membrane-embedded injectisomes. Based on these observations, we hypothesized that dynamic molecular turnover at the injectisome and cytosolic assembly among sorting platform proteins is a critical regulatory component of type 3 secretion. To determine whether sorting platform complexes exist in the cytosol, we measured the diffusive properties of the two central sorting platform proteins, SctQ and SctL, using live cell high-throughput 3D single-molecule tracking microscopy. Single-molecule trajectories, measured in wild-type and mutant Yersinia enterocolitica cells, reveal that both SctQ and SctL exist in several distinct diffusive states in the cytosol, indicating that these proteins form stable homo- and hetero-oligomeric complexes in their native environment. Our findings provide the first diffusive state-resolved insights into the dynamic regulatory network that interfaces stationary membrane-embedded injectisomes with the soluble cytosolic components of the type 3 secretion system.

Early detection and timely intervention are very essential for autism. This paper used the wavelet transform and empirical mode decomposition (EMD) to extract the features of electroencephalogram (EEG), to compare the feature differences of EEG between the autistic children and healthy children. The experimental subjects included 25 healthy children (aged 5-10 years old) and 25 children with autism (20 boys and 5 girls aged 5-10 years old) respectively. The alpha, beta, theta and delta rhythm wave spectra of the C3, C4, F3, F4, F7, F8, FP1, FP2, O1, O2, P3, P4, T3, T4, T5 and T6 channels were extracted and decomposed by EMD decomposition to obtain the intrinsic modal functions. Finally the support vector machine (SVM) classifier was used to implement assessment of autism and normal classification. The results showed that the accuracy could reach 87% and which was nearly 20% higher than that of the model combining the wavelet transform and sample entropy in the paper. Moreover, the accuracy of delta (1-4 Hz) rhythm wave was the highest among the four kinds of rhythms. And the classification accuracy of the forehead F7 channel, left FP1 channel and T6 channel in the temporal region were all up to 90%, which expressed the characteristics of EEG signals in autistic children better.

The antivitamin B 6 , 4'- O-methylpyridoxine (MPN); its glucoside, 4'- O-methylpyridoxine-5'-glucoside (MPNG); and vitamin B 6 compounds, including pyridoxal (PL), pyridoxamine, pyridoxine, pyridoxal-5'-phosphate (PLP), and pyridoxamine-5'-phosphate, exist in Ginkgo biloba seeds, which are widely used as food and medicine. This work aimed to determine the MPN analogues in G. biloba seeds at different growth stages in terms of cultivars and ages of trees. The highest total MPN contents of 249.30, 295.62, and 267.85 μg/g were obtained in the mature stages of three selected G. biloba samples. The total contents of vitamin B 6 compounds decreased significantly in the entire growth period of the three samples. Principal-component analysis revealed that MPN and MPNG were important contributors in the MPN-analogue metabolism of G. biloba seeds. The influence of the cultivar on the content and composition of MPN analogues was greater than that of the age of the G. biloba tree.

It is reported that sesquiterpenoids from Panax ginseng (SPG) possess various pharmacological activities, for example, antidepressant, antioxidative, and anti-inflammatory activities. The purpose of this study was to examine the hepatoprotective effects of SPG (2.5 and 10 mg/kg, i.g.) on fulminant liver injury induced by d-galactosamine (d-GalN) and lipopolysaccharide (LPS) and discuss its mechanisms of action. After 24 h of d-GalN (400 mg/kg, i.p.) and LPS (25 μg/kg, i.p.) exposure, the serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), hepatic malondialdehyde (MDA) level, hepatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and hepatic tissue histology were measured. Expression levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Moreover, the nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuin type 1 (Sirt 1), and heme oxygenase 1 (HO-1) were determined by western blotting. The results indicated that SPG evidently restrained the increase of serum ALT and AST levels induced by d-GalN/LPS. SPG obviously downregulated TNF-α and IL-1β levels and their mRNA expression in liver. In addition, d-GalN/LPS injection induced severe oxidative stress in liver by boosting the MDA level as well as decreasing CAT, GSH, and SOD capacities, and SPG reversed these changes. Meanwhile, SPG inhibited NF-κB activation induced by d-GalN/LPS and upregulated Sirt 1, Nrf2, and HO-1 expression levels. Therefore, SPG might protect against the fulminant liver injury induced by d-GalN/LPS via inhibiting inflammation and oxidative stress. The protective effect of SPG on fulminant liver injury induced by d-GalN/LPS might be mediated by the Sirt 1/Nrf2/NF-κB signaling pathway. All of these results implied that SPG might be a promising food additive and therapeutic agent for fulminant liver injury.

Objective: Cyclosporine (CsA) is a substrate of cytochrome P450 (CYP) 3A4 with a narrow therapeutic index and large individual difference. CYP3A4*1B is reported to be associated with CsA pharmacokinetics parameters, but the relevance is still in dispute. Therefore, a meta-analysis was employed to evaluate the influence of CYP3A4*1B on CsA pharmacokinetics at different post-transplantation times in adult renal transplant recipients., Methods: Studies on evaluating the CYP3A4*1B genotype and CsA pharmacokinetics were retrieved through a systematical search of relevant database including PubMed, Emabase, Web of science, the Cochrane Library, Clinical Trials.gov and three Chinese literature databases (up to 15 October 2017). The pharmacokinetic parameters: weight-adjusted CsA daily dose (Dose), cyclosporine trough concentration (C0) and trough concentration/weight-adjusted CsA daily dose ratio (C0/Dose ratio) were extracted, and all statistical analysis were performed by using Review Manager 5.1.0., Results: Four studies (involving 452 adult renal transplant recipients) were included in this meta-analysis. For the C0/Dose ratio, in all included renal transplant recipients, CYP3A4*1B carriers exhibited higher C0/Dose ratio than CYP3A4*1 (WMD 7.38, 95% CI 1.26-13.51; P = 0.02). The differences between CYP3A4*1B carriers and CYP3A4*1 in Dose (WMD 0.36, 95% CI 0.85-0.12; P = 0.14), C 0 (WMD 10.81, 95% CI 77.72-99.34; P = 0.81) were not statistically significant. According to post-transplantation time, subgroup analysis also showed no significant statistical significance between CYP3A4*1B carriers and CYP3A4*1 carriers in Dose or C 0 . However, this result should be further explored because only four studies were included., Conclusions: CYP3A4*1B is associated with CsA C0/Dose ratio in renal transplant recipients which indicates patients with CYP3A4*1B allele require lower dose of CsA to reach target blood concentration compared with the CYP3A4*1 carriers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Autism spectrum disorders (ASD) is a complex developmental disorder characterized by impairments in social communication and stereotyped behaviors. Electroencephalograph (EEG), which can measure neurological changes associated with cortical synaptic activity, has been proven to be a powerful tool for detecting neurological disorders. The main goal of this study is to explore the effects of repetitive transcranial magnetic stimulation (rTMS) on behavioral response and EEG. We enrolled 32 autistic children, rTMS group ( n = 16) and control group ( n = 16) and calculated the relative power of the δ, θ, α, β rhythms in each brain area by fast Fourier transform and Welch's method. We also compared Autism Behavior Checklist (ABC) scores of the patients before and after rTMS. The results showed a significant decrease in the relative power of the δ band on right temporal region and parietal region and also a decreased coherence on frontal region after rTMS intervention. The study proves that rTMS could have positive effects on behavior of attention, execution ability, and language ability of children and could reduce their stereotyped behavior and radical behavior.

Enhancer of zeste homolog 2 (EZH2), which is overexpressed in a wide range of tumors, contributes to ovarian cancer malignancy in several different ways. We aimed to illustrate the role of EZH2 in ovarian cancer cisplatin resistance and to identify possible underlying mechanisms of this role that may provide a rationale for targeting EZH2 in cancer treatment. Here, we present data indicating that EZH2 overexpression is associated with cisplatin resistance and intracellular platinum drug accumulation. Measurements of EZH2 in 84 ovarian cancer patients suggested that patients with high EZH2 levels tend to have poor responses to cisplatin. The EZH2 level progressively increased in cells receiving repeated cisplatin exposure. Downregulation of EZH2 not only sensitized cellular reactions to cisplatin and increased cellular platinum accumulation when cells were exposed to both cisplatin and BODIPY-Pt (a fluorescent cisplatin complex) but also protected copper transporter 1, a high-affinity copper transporter closely related to cisplatin resistance, from cisplatin-induced proteasomal degradation. Overall, these findings identify a new mechanism that expands the unrecognized role of EZH2 in ovarian cancer cisplatin resistance., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The oxidative stress and inflammatory response play an important role in carbon tetracholoride (CCl 4 )-induced acute liver injury. In this work, sesquiterpenoids from the root of Panax Ginseng (SPG) were prepared, and then the hepatoprotective effects of SPG against CCl 4 -induced acute liver injury were investigated and the underlying mechanism was explored in mice. All mice were divided into four groups: the control, CCl 4 and SPG (2.5 and 10 mg/kg, dissolved in soybean oil, i.g.) groups. All mice were given continuous administration for 7 days, and injected with CCl 4 (0.1 mL/10 g body weight 0.2% CCl 4 solution in soybean oil, i.p.) 1 h after the end of the administration except the control group. Mice were sacrificed 24 h post-CCl 4 injection. The results indicated that SPG significantly reduced the increasement of serum AST and ALT levels induced by CCl 4 -treatment. And the histopathological analysis revealed that SPG treated mice had normal liver architecture and no necrosis. The decreased activities of SOD, GSH and CAT, and increased MDA level were inhibited by SPG treatment. At the same time, the levels of TNF-α, IL-1β and IL-6 were significantly decreased by SPG treatment. SPG treatment also reduced the heptic protein expressions of NF-κB p65, COX-2, MAPK p38, ERK and JNK in the liver. These fingdings demonstrated that SPG exhibited strong hepatoprective effect on the CCl 4 -induced acute liver injury, which was related to anti-oxidantive and anti-inflammatory capabilities; and the anti-inflammatory effect of SPG might mediated by the NF-κB and MAPKs signaling pathways. Taken together, SPG might be a potential material for drug and functional food development against chemical hepatic injury., (Copyright © 2018. Published by Elsevier Masson SAS.)