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In order to effectively attenuate the inherent hysteresis nonlinearity of magneto-rheological (MR) dampers, and achieve precise tracking control of damping force, a cascaded control strategy based on Hammerstein model is proposed in this paper. A BP neural network is utilized to construct the nonlinear module of Hammerstein model, which accurately captures the hysteresis behavior of MR dampers. The dynamic characteristics of the dampers are then described by a linear time-invariant model. For MR dampers, the cascaded control strategy enhances the robustness of the system compared to traditional open-loop control based on the inverse model schemes. The effectiveness of the proposed control algorithm has been verified through simulation experiments and hardware-in-the-loop experiments using a seat suspension testbed equipped with MR dampers. [ABSTRACT FROM AUTHOR]

Bioremediation, mainly by indigenous bacteria, has been regarded as an effective way to deal with the petroleum pollution after an oil spill accident. The biodegradation of crude oil by microorganisms co-incubated from sediments collected from the Penglai 19-3 oil platform, Bohai Sea, China, was examined. The relative susceptibility of the isomers of alkylnaphthalenes, alkylphenanthrenes and alkyldibenzothiophene to biodegradation was also discussed. The results showed that the relative degradation values of total petroleum hydrocarbon (TPH) are 43.56% and 51.29% for sediments with untreated microcosms (S-BR1) and surfactant-treated microcosms (S-BR2), respectively. TPH biodegradation results showed an obvious decrease in saturates (biodegradation rate: 67.85–77.29%) and a slight decrease in aromatics (biodegradation rate: 47.13–57.21%), while no significant difference of resins and asphaltenes was detected. The biodegradation efficiency of alkylnaphthalenes, alkylphenanthrenes and alkyldibenzothiophene for S-BR1 and S-BR2 samples reaches 1.28–84.43% and 42.56–86.67%, respectively. The efficiency of crude oil degradation in sediment with surfactant-treated microcosms cultures added Tween 20, was higher than that in sediment with untreated microcosms. The biodegradation and selective depletion is not only controlled by thermodynamics but also related to the stereochemical structure of individual isomer compounds. Information on the biodegradation of oil spill residues by the bacterial community revealed in this study will be useful in developing strategies for bioremediation of crude oil dispersed in the marine ecosystem. [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsA) and nitric oxide (NO) are well known and widespread antioxidants and gaseous molecules that regulate plant tolerance to several stresses. However, the relationship between them in plant response to stress, especially heavy stress, is largely unclear. This study demonstrated that both AsA and NO could enhance the tolerance of wheat seedlings to cadmium stress evidenced by root length change, which resulted from their roles in maintaining the balance in reactive oxygen species (ROS) and reducing the absorption of Cd. Furthermore, exogenous AsA led to a significant increase of NO content and endogenous AsA content in wheat roots, which could be weakened by the NO scavenger c-PTIO. In addition, c-PTIO also inhibits the NO-induced production of endogenous AsA. Although the AsA synthesis inhibitor lycorine significantly inhibited the inductive effect of exogenous AsA on endogenous AsA production, it has little effect on NO content. In addition, we found that the protective effects of NO and AsA on Cd stress were removed by c-PTIO and lycorine. These results indicated that NO accumulation could be necessary for exogenous AsA-induced cadmium tolerance and endogenous AsA production, and the exogenous AsA-induced endogenous AsA production was likely mediated by NO signaling pathways and together they induced the tolerance of wheat to cadmium stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel series of AP2238-clorgiline hybrids as anti-Alzheimer agents has been designed and synthesized. • 5l showed the balanced and good inhibitory activity against AChE, BuChE and MAO-B. • 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 μM and no acute toxicity at a dosage of 2500 mg/kg. • 5l could significantly reverse scopolamine-induced memory deficit in mice and penetrate the BBB. Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (ee AChE: IC 50 = 4.03 ± 0.03 μM, eq BuChE: IC 50 = 5.64 ± 0.53 μM; h AChE: IC 50 = 8.30 ± 0.04 μM, h BuChE: IC 50 = 1.91 ± 0.06 μM) and h MAO-B (IC 50 = 3.29 ± 0.09 μM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 μM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood–brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Although compact urban form plays an important role in constraining emissions of carbon dioxide (CO 2), the boundary for the impact of compact urban form on these emissions has nevertheless received little attention. We consequently applied the entropy weight method and several key landscape metrics to a dataset from 295 cities in China to quantify urban form compactness (UFC) between 2000 and 2015. The STIRPAT model then was employed to estimate the impact of UFC on CO 2 emissions, and a panel threshold regression model was used to estimate threshold effects capable of limiting the impact of compact urban form on emissions. Although CO 2 emissions increased sharply over the 15-year study period, a significant negative relationship between UFC and CO 2 emissions was detected. Two thresholds of UFC were detected, and this allowed three categories to be differentiated: before the first threshold, between the two thresholds, and after the second threshold. These categories were respectively associated with no impact, strong impact, and weak impact of UFC on reduction of carbon emissions in the 295 cities. Carbon emissions reduction consequently becomes effective when the UFC exceeds the first threshold and effectiveness persists but at a reduced level when the UFC exceeds the second threshold. Further temporal analysis confirmed that an increasing number of mostly small- and medium-sized cities could constrain their future carbon emissions by adopting a compact urban form. Thus, government policies should emphasize UFC as a strategy to reduce CO 2 emissions. Moreover, by defining the range of compact urban form that has the greatest impact on CO 2 emissions, our study deepens the overall understanding of the influence of UFC on carbon emission reductions, so as to make contributions to the design of low-carbon cities. [Display omitted] • The panel threshold regression model was employed. • Urban form compactness (UFC) had negative relationship with CO 2 emissions. • The impact of UFC on CO 2 emissions had two threshold points. • Three impact intervals (no, strong, and weak) of UFC on CO 2 emissions were defined. • Urban planners should optimize carbon reduction by pursing moderate UFC as a goal. [ABSTRACT FROM AUTHOR]

We report a simple and rapid method to fabricate superhydrophobic films on copper substrates via Fe 3+ etching and octadecanethiol (ODT) modification. The etching process can be as short as 5 min and the ODT treatment only takes several seconds. In addition, the whole process is quite flexible in reaction time. The superhydrophobicity of as-prepared surfaces is mechanically durable and chemically stable, which have great performance in oil–water separation and ice-over resistance. [ABSTRACT FROM AUTHOR]

The development of optics and computer technologies enables the application of the vision-based technique that uses digital cameras to the displacement measurement of large-scale structures. Compared with traditional contact measurements, vision-based technique allows for remote measurement, has a non-intrusive characteristic, and does not necessitate mass introduction. In this study, a high-speed camera system is developed to complete the displacement measurement in real time. The system consists of a high-speed camera and a notebook computer. The high-speed camera can capture images at a speed of hundreds of frames per second. To process the captured images in computer, the Lucas–Kanade template tracking algorithm in the field of computer vision is introduced. Additionally, a modified inverse compositional algorithm is proposed to reduce the computing time of the original algorithm and improve the efficiency further. The modified algorithm can rapidly accomplish one displacement extraction within 1 ms without having to install any pre-designed target panel onto the structures in advance. The accuracy and the efficiency of the system in the remote measurement of dynamic displacement are demonstrated in the experiments on motion platform and sound barrier on suspension viaduct. Experimental results show that the proposed algorithm can extract accurate displacement signal and accomplish the vibration measurement of large-scale structures. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a global environmental contaminant, and excessive mercury levels in water can adversely affect the growth of fish. Silver carp (Hypophthalmichthys molitrix) is one of the important freshwater aquaculture fish in China, and its natural resources have been critically declining. However, the effects of Hg2+ exposure on the growth hormone/insulin-like growth factor (GH/IGF) axis and its toxic mechanism are still unclear. In this study, we systematically evaluated the bioaccumulation, histomorphology, antioxidant status, hormone levels, and GH/IGF axis toxicity of juvenile silver carp after exposure to environmental-related concentrations of Hg2+ (0, 0.05, 0.5, 5, and 50 µg/L) for 28 days. Results showed that the Hg2+ bioaccumulation in the liver increased with a rise in Hg2+ concentration and time of exposure. The body length (BL), body weight (BW), weight growth rate (WGR) and specific growth rate (SGR) all decreased after Hg2+ exposure. The serum levels of growth hormones (GH and IGF) and thyroid hormones (T3 and T4) were significantly decreased, and the expressions of GH/IGF axis-related genes were significantly downregulated after 7, 14, and 28 days of Hg2+ exposure. Correlations between the growth parameters and growth hormones or expression of genes in GH/IGF axis further suggested that environmentally relevant concentrations of Hg2+ could have adverse effects on growth. In addition, with increasing Hg2+ exposure, superoxide activities of dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were significantly increased, whereas the activity of glutathione peroxidase (GPx) significantly decreased and oxidative stress-related gene significantly changed. Liver lesions were mainly characterized by inflammatory cell infiltration, hepatocyte necrosis and fat vacuolation after exposure to Hg2+. Taken together, the results indicate that Hg2+ exposure leads to growth inhibition and oxidative stress in juvenile silver. • Mercury exposure caused histological alterations of liver • Mercury exposure induced the antioxidant defense of liver. • Mercury exposure alters GH/IGF axis-related genes expression of juvenile silver carp. • Growth of juvenile silver carp was inhibited by environmentally relevant levels of mercury. [ABSTRACT FROM AUTHOR]

IL-17, the hallmark cytokine of Th17 cells, plays a pivotal role in the pathogenesis of autoimmune diseases, including encephalomyelitis. In the central nervous system, neuroglial cells are the main residents that express IL-17R and respond to IL-17 by producing chemokines/cytokines and boosting local inflammation. Factors that influence the IL-17R expression in neuroglial cells can also exert their impacts on the outbreak, progression and outcome of encephalomyelitis. Here, we reported that Toll-like receptor signaling has its bias for promoting the IL-17RA, but not the IL-17RC, expression in mouse neuroglial cells in a T cell infiltration independent manner. Elevated IL-17R functionally responded to IL-17 by secreting more chemokines and accelerating CD4 cell migration. First, real-time PCR confirmed that the expression of Il-17ra , but not Il-17rc , was significantly increased in the brain and spinal cord of EAE-induced mice. This effect was elicited by something in complete Freund's adjuvant (CFA), because markedly increased IL-17R was detected in mice immunized with CFA only, even though no evidence of EAE was found. Furthermore, in Rag1 −/− mice, it was confirmed that CFA could augment the IL-17RA expression in the CNS in the absence of T cell infiltration. In vivo immunization with TLR ligands and in vitro treatment of purified neuroglial cells demonstrated that TLR ligands directly and effectively evoke the IL-17RA expression in the CNS and in cultured astrocytes, microglia and oligodendrocytes. LPS was the most effective inducer of the IL-17RA expression in astrocytes, and polyIC was superior to LPS for microglia and oligodendrocytes. Activated CD4 cells can also promote the secretion of chemokines by LPS pre-treated astrocytes, and hence accelerate the migration of CD4 cells, which was blocked by the neutralization of IL-17RA on the surface of the astrocyte. Taken together, we concluded that TLR signaling can directly stimulate the expression of IL-17RA, but not IL-17RC, in neuroglial cells, which functionally respond to IL-17A by secreting chemokines, accelerating CD4 cell migration, and contributing to the pathogenesis of encephalomyelitis. [ABSTRACT FROM AUTHOR]

Highlights: [•] A fiber laser with a PID-SESAM or a PD-SESAM is constructed for obtaining vector soliton bunching. [•] Only the vibrating soliton bunching is generated from the fiber laser with a PID-SESAM. [•] There are abundant temporal patterns of soliton bunching generated from the fiber laser with a PD-SESAM. [•] The polarization property of the saturable absorber plays a pivotal role for achieving different temporal patterns. [Copyright &y& Elsevier]

Highlights: [•] DBP in wine determined by lumniol–Mb CL system for first time. [•] DBP quenches the CL intensity of lumniol–Mb system. [•] The CL intensity decrements are logarithmic over DBP concentrations. [•] The determination of DBP at picogram levels by FI–CL proposed for first time. [•] FI–CL method is simple, fast and sensitive for detecting DBP in wine. [Copyright &y& Elsevier]

Lead (Pb) widely exists in the water environment and has severe toxic effects on aquatic organisms. The yellow catfish (Pelteobagrus fulvidraco) is one of the most important commercial species in China, and moreover, its natural populations are declining with the degradation of environmental water quality. However, little is known about the toxic effects of Pb on its immune organs. This study was performed to determine waterborne Pb exposure on bioaccumulation, histomorphology, antioxidant status, apoptotic and immune response in the head kidney and spleen of yellow catfish. Experimental fish were randomly allocated into twelve tanks (3 tanks per group), and the Pb concentrations of the four groups were 0, 5, 50, and 500 μg/L, respectively. The results reflected that the Pb bioaccumulation of the head kidney and spleen increased with increasing Pb exposure dose and time. Severe histological alterations in the head kidney and spleen were observed at concentration 500 ug/L. With increasing Pb exposure concentrations, the plasma activity of superoxide dismutase (SOD) and catalase (CAT) significantly increased after exposure 7 days and 14 days, and the levels significantly decreased after exposure 28 days. The change trend of glutathione (GSH) levels was opposite to that of SOD and CAT at corresponding exposure time. The plasma malondialdehyde (MDA) levels together with the activities of plasma alkaline phosphatase (AKP) and acid phosphatase (ACP) increased significantly with the increasing Pb concentrations. In contrast, the levels of lysozyme (LYZ), complement 3 (C3) and immunoglobulin M (IgM) decreased significantly with increasing Pb concentrations. Moreover, Pb exposure induced transcriptional upregulation of heat shock protein 70 (hsp70), metallothionein (mt), sod , cat , interleukin-10 (il-10), transforming growth factor-β (tgf-β), and tumor necrosis factor-α (tnf-α), bcl-2-associated X protein (bax), and cysteinyl aspartate specific proteinase - 9 (caspase-9), genes in the head kidney and spleen tissues, while downregulating the levels of the lyz , c3 , igm and B-cell lymphoma-2 (bcl-2) genes. Our data provide evidence that Pb impaired immune function and tissue integrity in yellow catfish through oxidative stress, inflammatory and apoptosis, and the results can serve as reference data to better protect water environments from Pb eco-toxicants. • Pb impaired immune function and tissue integrity in yellow catfish. • Pb induced oxidative stress followed similar trend in the head kidney and spleen. • Immunological indices in the high concentration group changed significantly with time. • The environmentally-relevant concentration (≥50 μg/L) could induce immunosuppression. [ABSTRACT FROM AUTHOR]

[Display omitted] • The most potent compound 12a displayed good inhibitory activity on HeLa cancer cells, and caused depolarization of mitochondrial membrane potential, enhancement of ROS levels and apoptosis in HeLa cells. • 12a induced G0/G1 cell cycle arrest in HeLa cells. • 12a significantly decreased OCR and ATP production of HeLa cells. With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria. [ABSTRACT FROM AUTHOR]

[Display omitted] Lithium-oxygen batteries (LOBs) with a theoretical energy density of up to 3500 Wh kg−1 hold a promise for the next-generation high-energy-density batteries. However, the slow oxygen reduction/evolution kinetics at the cathode limits the performance of Li-air batteries. The rational design of efficient catalysts is essential for the improvement of oxygen electrode reaction kinetics. Herein, we report a facile strategy to co-dope N and P atoms simultaneously into Ti 3 C 2 T x (NP-Ti 3 C 2 T x) MXene via an electrostatic self-assembly approach. The co-doped NP-Ti 3 C 2 T x layers expose abundant active sites, providing more space for accommodating the formed Li 2 O 2. Moreover, the N and P co-doping facilitates efficient electron transport in Ti 3 C 2 T x MXene. The LOB with NP-Ti 3 C 2 T X catalyst delivers a high discharge capacity of 24,940 mAh/g at 1000 mA g−1. At a cut-off capacity of 1000 mAh/g, this battery runs continuously for 159, 276, 185, and 229 cycles at current densities of 1000, 2000, 3000, and 5000 mA g−1, respectively. Theoretical calculations unveil that N and P co-doping enables lower ηORR and ηOER of only 0.26 V and 0.13 V on Ti 3 C 2 T x MXene, respectively. This work offers a feasible approach for constructing efficient MXene electrocatalysts for Li–air batteries. [ABSTRACT FROM AUTHOR]

Photocatalytic technology assisted via peroxymonosulfate (PMS) has good potential in water treatment. In this study, the Co 3 O 4 /Bi 2 WO 6 composite was constructed via an in-situ calcination process and used to activate PMS for the degradation of ciprofloxacin (CIP) under visible light irradiation. The obtained 5 wt% Co 3 O 4 /Bi 2 WO 6 (CBWO-2) can highly effectively remove 86.2% CIP within 5 min visible light irradiation in presence of PMS. The excellent degradation performance of Co 3 O 4 /Bi 2 WO 6 /PMS system can be attributed to the synergistic effect between p-n heterojunction and PMS activation. The conduction band and valence band deviation between Co 3 O 4 and Bi 2 WO 6 were calculated by XPS techniques. Besides, DFT calculations were performed to further confirm the internal structure between Co 3 O 4 and Bi 2 WO 6. This work not only provides an approach to fabricate heterostructures but also indicated that Co 3 O 4 /Bi 2 WO 6 /PMS/Vis system is a potential environment remediation alternative for the efficient removal of recalcitrant organic compounds from wastewaters. [ABSTRACT FROM AUTHOR]

We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11 • REBACIN is safe and effective for eliminating persistent high-risk HPV infection in a real-world clinical setting. • HPV16/18 is cleared more easily than HPV52/58. • Single-type infections are cleared more easily than multiple-type infections. • Young patients have a higher clearance rate than older patients. • Providing valuable guidance for clinical use of REBACIN while also suggesting potential areas for future basic research. [ABSTRACT FROM AUTHOR]

The effects of long-term rosuvastatin treatment on the regulation of cytochrome P450 (CYP) 4A1 expression and vascular homeostasis of spontaneously hypertensive rat (SHR) are still unknown. In this study SHRs were randomly divided into three groups (n = 10 per group): SHR group, H-Rv group (rosuvastatin 2.5 mg·kg − 1 ·d − 1 ), L-Rv group (rosuvastatin 0.5 mg·kg − 1 ·d − 1 ), and 10 male Wistar–Kyoto (WKY) rats in the control group (WKY group). All rats were treated with rosuvastatin for 12 weeks. The systolic blood pressure (SBP), left ventricle weight index (LVWI) and plasma lipids were measured during or after treatment. The expression of CYP4A1 mRNA and protein in different tissues was detected by real-time PCR and Western blot. In the heart, kidney and aorta, the CYP4A1 expressions were down-regulated at both mRNA and protein levels in rosuvastatin-treated groups compared with the untreated SHR group (P < 0.05 or P < 0.01), and high-dose rosuvastatin exerted a stronger down-regulatory effect. The increasing trend of blood pressure was markedly blunted in the rosuvastatin-treated groups versus the untreated SHR group, and a stronger effect was observed in high-dose group (P < 0.05 and P < 0.01 at different time points). LVWI, an indicator of ventricle hypertrophy, was improved in the high-dose group compared with the untreated SHR group (P < 0.05). The plasma concentrations of TC, TG and LDL-C in three SHR groups (high-dose, low-dose and untreated group) were all significantly lower than those of WKY group (P < 0.05 or P < 0.01), which seemed unrelated to the treatment of rosuvastatin. These findings suggested that hypertension in SHRs was possibly associated with CYP4A1 overexpression, and the effects of rosuvastatin on blood pressure and ventricle hypertrophy were potentially correlated with CYP4A1 and its metabolite other than lipid profiles. Multiple mechanisms are likely involved in the beneficial effects of statins with respect to the regulation of CYP4A1. [ABSTRACT FROM AUTHOR]

The saponins found in Panax japonicus , a traditional medicinal herb in Asia, exhibit high degrees of structural and functional similarity. In this study, metabolite analysis revealed that oleanolic acid-type and dammarane-type saponins were distributed unevenly in three tissues (rhizome_Y, rhizome_O, and secRoot) of P. japonicus. Single-molecule real-time (SMRT) sequencing and next generation sequencing (NGS) data revealed distinct and tissue-specific transcriptomic patterns relating to the production of these two types of saponins. In the co-expression network and hierarchical clustering analyses, one 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and two 1-deoxy-D-xylulose-5-phosphate synthase (DXS) etc. transcripts were found to be key genes associated with the biosynthesis of oleanolic acid and dammarane-type saponins in P. japonicus, respectively. In addition, cytochrome p 450 (CYP) and UDP-glucuronosyltransferase (UGT) family proteins that serve as regulators of saponin biosynthesis-related genes were also found to exhibit tissue-specific expression patterns. Together these results offer a comprehensive metabolomic and transcriptomic overview of P. japonicus. • Metabolite analysis revealed oleanolic acid and dammarane-type saponins were distributed unevenly in different tissues of P.japonicus • DEGs analysis combining long read transcriptome and next generation sequencing was reported in P.japonicus firstly. • WGCNA confirmed that the pivotal CYP and UGT transcripts regulate the oleanolic acid and dammarane-type saponins distribution in different tissues of this drug plants. [ABSTRACT FROM AUTHOR]

Due to TRAIL's explicit cancer cell-selectivity, the current study aimed to explore novel agents that sensitized cancer cell for TRAIL-induced apoptosis while sparing normal cell. In this study, we found that TRAIL could induce PARP-1 cleavage and apoptosis in colon cancer HCT116 cell, but HT-29 cell was not sensitive to TRAIL. However, non-cytotoxic doses of ipatasertib in conjunction with TRAIL could induce apoptosis in HT-29 cell. Mechanism studies showed that intracellular ROS level was significant increased during ipatasertib treatment. Excessive cellular levels of ROS further induced DNA damage and subsequently activated apoptotic signaling pathways in TRAIL-resistant HT-29 cells. Combined treatment with sub-toxic doses of ipatasertib and TRAIL leads to caspase activation and PARP-1 cleavage in HT-29 cells. Pretreated with NAC, an antioxidant, could inhibit ROS production and PARP-1 cleavage as well as prevent cell apoptotic death induced by combination therapy with TRAIL and ipatasertib. In addition, NAC can block the up-regulation of p53/PUMA induced by combined treatment with ipatasertib and TRAIL. Transfection with p53 or Puma siRNA for 48 h can reverse ipatasertib-mediated TRAIL sensitization. In conclusion, p53 and PUMA may play a pivotal role in sensitizing colon cancer cell to TRAIL-induced apoptosis by sub-toxic doses of ipatasertib treatment. Image 105 • TRAIL could induce apoptosis in colon cancer HCT116 cell but HT-29 cell was not sensitive to TRAIL. • Combined treatment with sub-toxic doses of ipatasertib and TRAIL leads to caspase activation and PARP-1 cleavage in HT-29 cells via promoting p53 and PUMA expression. [ABSTRACT FROM AUTHOR]

Dexamethasone (DEX), a widely used glucocorticoid with strong anti-inflammatory and immunosuppressive activities, has been reported to induce apoptosis in osteoblasts, but the underlying mechanisms are still not comprehensively investigated. FOXO1 plays an important role in the regulation of cell proliferation and apoptosis. Our study aims to explore the role of FOXO1 in DEX-induced apoptosis of osteoblastic MC3T3-E1 cells through bioinformatics and experiments. We first employed bioinformatics to identify DEX-related genes and revealed their functions by GO enrichment analysis including FOXO1 associated biological processes. Expression level of FOXO1 was validated by GEO data. Then, experiments were performed to verify the hypothesis. CCK8 was used to detect cell viability and apoptosis was detected by flow cytometry. SiRNA was used to silence FOXO1 and western-blot was employed to detect protein expression. Results demonstrated DEX-related genes involved in cell proliferation, apoptosis and angiogenesis and FOXO1 was a regulator of apoptosis. DEX could up-regulate FOXO1 expression, inhibit cell viability, promote apoptosis. SiRNA-FOXO1 could attenuate DEX-induced apoptosis in MC3T3-E1. These findings suggested DEX could affect some vital biological processes of MC3T3-E1 and FOXO1 played an essential role in DEX-induced apoptosis in MC3T3-E1. ● Combination of bioinformatic analysis and experiments validation. ● Dex inhibits cell viability and induces apoptosis of MC3T3-E1 osteoblasts. ● Dexamethasone (Dex) increases FOXO1 expression in MC3T3-E1 osteoblasts. ● Silencing FOXO1 attenuates dexamethasone-induced apoptosis in MC3T3-E1 osteoblasts. [ABSTRACT FROM AUTHOR]

Neuronal gastrin-releasing peptide (GRP) has been proved to be an important neuromodulator in the brain and involved in a variety of neurological diseases. Whether GRP could attenuate cognition impairment induced by vascular dementia (VD) in rats, and the mechanism of synaptic plasticity and GRP's action on synaptic efficiency are still poorly understood. In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial learning and memory abilities in VD rats, restored the impaired synaptic plasticity and was able to elevate the expression of synaptic proteins, synaptophysin (SYP) and CaMKII, which play pivotal roles in synaptic plasticity. These results suggest that the facilitatory effects of GRP on glutamate release may contribute to its long-term action on synaptic efficacy which is essential in cognitive function. Our findings present a new entry point for a better understanding of physiological function of GRP and raise the possibility that GRPR agonists might ameliorate cognitive deficits associated with neurological diseases. [ABSTRACT FROM AUTHOR]

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Paenibacillus terrae PY8 has a signficant antagonistic effect on Botrytis cinerea. • Foliar application of PY8 increased the content of polyphyllin Ⅰ and Ⅱ. • PY8 favorably altered the endophytic microbiome of Paris polyphylla. Huachonglou (Paris polyphylla Smith var. chinensis (Franch.) Hara) is an important traditional Chinese herbal medicine. Botrytis cinerea is a plant pathogen that causes significant economic losses of P. polyphylla. Presently, chemical fungicides are the primary means of effective control of gray mold caused by B. cinerea. As a safer and greener control method, biocontrol agents (BCAs) for gray mold of P. polyphylla are very important. In the present study, a biocontrol agent, Paenibacillus terrae PY8, was isolated from the endophytic microbial community of leaves of the medicinal plant, Paris polyphylla. PY8 significantly reduced gray mold infections by Botrytis cinerea and additionally increased P. polyphylla yield and the level of polyphyllin Ⅰ and Ⅱ of P. polyphylla detected in rhizomes. An analysis of the endophytic microbial community of leaves of P. polyphylla indicated that the foliar application of P. terrae PY8 favorably altered the composition and structure of the endophytic community in P. polyphylla by decreasing the total abundance of potential plant pathogenic fungi. The effect of biocontrol agents on the endophytic microbiome may represent a new criterion for evaluating biocontrol agents in the future. Results of the present study provide theoretical support for the field application of PY8 on P. polyphylla for the control of gray mold. [ABSTRACT FROM AUTHOR]

A series of novel coumarin-based N -hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity against human cancer cell lines MCF-7, HepG2, HeLa and HCT-116. Among them, compound 14f displayed the most potent HDAC inhibition, especially against HDAC1 with IC 50 value of 0.19 μM, which was better than that of SAHA (IC 50 = 0.23 μM). It also showed the strongest antiproliferative activity towards HeLa cells and more than 26-fold selectivity for HDAC1 compared with HDAC6. Molecular docking studies revealed the possible binding modes of compound 14f into the two isoforms and provided a reasonable explanation for the selectivity. In addition, compound 14f could inhibit colony formation, upregulate the acetylation level of histone H3, and induce apoptosis and cell cycle arrest at G2/M phase in HeLa cells. Taken together, these results highlighted that compound 14f might be a promising HDAC inhibitor for cancer therapy. [ABSTRACT FROM AUTHOR]