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The aim of this study was to develop a population pharmacokinetic (PK) model to simultaneously describe both total and unbound concentrations of ciprofol and its major glucuronide metabolite, M4, and to link it to the population pharmacodynamics (PD) model in subjects with various renal functions.A total of 401 and 459 pairs of total and unbound plasma concentrations of ciprofol and M4, respectively, as well as 2190 bispectral index (BIS) data from 24 Chinese subjects with various renal functions were available. Covariates that may potentially contribute to the PK and PD variability of ciprofol were screened using a stepwise procedure. The optimal ciprofol induction dosing regimen was determined by model-based simulations.The PK of unbound ciprofol could best be described by a three-compartment model, while a two-compartment model could adequately describe unbound M4 PK. The concentrations of total and unbound ciprofol and M4 were linked using a linear protein binding model. The relationship between plasma concentrations of ciprofol and BIS data was best described by an inhibitory sigmoidal EThe developed model fully characterized the population PK and PD profiles of ciprofol. No dose adjustment is required in patients with mild and moderate renal impairment.

Background Current polymyxin B dosing in children relies on scant data. Objectives To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. Methods A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. Results PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were Conclusions Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC.We carried out a systematic review on lncRNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lncRNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in PubMed with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lncRNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed.LncRNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting miRNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process.The functional lncRNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

Background: Along with the medical team, clinical pharmacists played a significant role during the public health emergency of COVID-19. However, to our knowledge, few studies on their work experience with combating COVID-19 have been published. Interviews with clinical pharmacists was conducted to better understand their roles. Through these interviews, further insight would be gained regarding the existing problems within pharmaceutical departments in medical institutions. This information could be used to amend emergency plans for when these departments encounter catastrophic public health events. Methods: A qualitative study design was employed with face-to-face and audio-recorded interviews being conducted with 13 clinical pharmacists. This group included nutritional pharmacists from two hospitals that were fighting against COVID-19 in Henan. All interviews were transcribed verbatim, and the interview data were analyzed thematically using Colaizzi software (version 11). Results: The results contributed to a deeper understanding of the clinical pharmacists’ work experiences providing consultation for the medical department. Four themes emerged from interview data, including the role played by clinical pharmacists, experiences encountered by clinical pharmacists, psychological feelings of clinical pharmacists, and career expectations of clinical pharmacists. Conclusions: This exploratory study provides preliminary evidence that some of the work experiences of clinical pharmacists were aligned. However, some deficiencies, such as lack of participation, were highlighted by the clinical pharmacists and these deficiencies are areas that need to be improved by the department of pharmacy.

Biocatalysis in high-concentration organic solvents (OSs) offers many advantages, but realizing this process remains a huge challenge. An R-selective ω-amine transaminase variant (AcATA

To investigate why tailings piping break, identify the mechanisms of tailings dam breaches, and discover how mine tailings flood behave, a large-scale physical model of a tailings reservoir was constructed. The model tailings dam was breached and this breaching test was used to study dam breaching and the resulting tailings flood. The results show that a scour channel is formed in the dam by piping and then the upper portion of the dam collapses and lateral scour occurs. The breach goes through three stages: channel expansion, longitudinal undercutting, and transverse expansion. On the basis of these three stages, seven stages of dam breaching are proposed. The velocity of the tailings flood decreases logarithmically with distance. Three stages of dam breaking that include impact velocity, density, and burial depth are proposed based on a power function impact force model. Tailings flood undercut and erode near the dam and tailings are deposited farther away. The tailings flood direction changes at a bend and erosion occurs along the outer side of the bend while tailings are deposited near the inner side. Suggestions for tailings dam protection are put forward. The above research results provide an experimental and theoretical basis for disaster prevention and mitigation of tailings pond issues.

This study aims to investigate metabolic activities of psoralidin in human liver microsomes( HLM) and intestinal microsomes( HIM),and to identify cytochrome P450 enzymes( CYPs) and UDP-glucuronosyl transferases( UGTs) involved in psoralidin metabolism as well as species differences in the in vitro metabolism of psoralen. First,after incubation serial of psoralidin solutions with nicotinamide adenine dinucleotide phosphate( NADPH) or uridine 5apos;-diphosphate-glucuronic acid( UDPGA)-supplemented HLM or HIM,two oxidic products( M1 and M2) and two conjugated glucuronides( G1 and G2) were produced in HLM-mediated incubation system,while only M1 and G1 were detected in HIM-supplemented system. The CLintfor M1 in HLM and HIM were 104. 3,and57. 6 μL·min~(-1)·mg~(-1),respectively,while those for G1 were 543. 3,and 75. 9 μL·min~(-1)·mg~(-1),respectively. Furthermore,reaction phenotyping was performed to identify the main contributors to psoralidin metabolism after incubation of psoralidin with NADPH-supplemented twelve CYP isozymes( or UDPGA-supplemented twelve UGT enzymes),respectively. The results showed that CYP1 A1( 39. 5 μL·min~(-1)·mg~(-1)),CYP2 C8( 88. 0 μL·min~(-1)·mg~(-1)),CYP2 C19( 166. 7 μL·min~(-1)·mg~(-1)),and CYP2 D6( 9. 1 μL·min~(-1)·mg~(-1)) were identified as the main CYP isoforms for M1,whereas CYP2 C19( 42. 0 μL·min~(-1)·mg~(-1)) participated more in producing M2. In addition,UGT1 A1( 1 184. 4 μL·min~(-1)·mg~(-1)),UGT1 A7( 922. 8 μL·min~(-1)·mg~(-1)),UGT1 A8( 133. 0 μL·min~(-1)·mg~(-1)),UGT1 A9( 348. 6 μL·min~(-1)·mg~(-1)) and UGT2 B7( 118. 7 μL·min~(-1)·mg~(-1)) played important roles in the generation of G1,while UGT1 A9( 111. 3 μL·min~(-1)·mg~(-1)) was regarded as the key UGT isozyme for G2. Moreover,different concentrations of psoralidin were incubated with monkey liver microsomes( MkLM),rat liver microsomes( RLM),mice liver microsomes( MLM),dog liver microsomes( DLM) and mini-pig liver microsomes( MpLM),respectively. The obtained CLintwere used to evaluate the species differences.Phase Ⅰ metabolism and glucuronidation of psoralidinby liver microsomes showed significant species differences. In general,psoralidin underwent efficient hepatic and intestinal metabolisms. CYP1 A1,CYP2 C8,CYP2 C19,CYP2 D6 and UGT1 A1,UGT1 A7,UGT1 A8,UGT1 A9,UGT2 B7 were identified as the main contributors responsible for phase Ⅰ metabolism and glucuronidation,respectively. Rat and mini-pig were considered as the appropriate model animals to investigate phase Ⅰ metabolism and glucuronidation,respectively.

Mailuoshutong pill (MLSTP) is a traditional Chinese medicine (TCM) for the treatment of Thromboangiitis obliterans (TAO, Buerger's disease) which is a segmental non-atherosclerotic inflammatory occlusive disorder. However, the mechanism and quality standards of MLSTP have not been sufficiently studied.This work aims to investigate the potential mechanisms and quality markers (Q-markers) of MLSTP treating TAO based on the chinmedomics strategy.The therapeutical effect of MLSTP on TAO rats was evaluated by changes in body weight and clinical score, regional blood flow velocity and perfused blood vessel distribution, hematoxylin-eosin (HE) staining, serum metabolic profile. Moreover, both endogenous metabolites and exogenous components were simultaneously detected in serum based on ultra-high performance liquid chromatography coupled with a Q Exactive hybrid quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and multivariate analysis was applied to identify the biomarkers, as well as the dynamic changes of metabolites were observed to explore the mechanism of action of MLSTP. In addition, the pharmacodynamic material basis were identified by correlation analysis between biomarkers and absorbed constituents. Finally, the Q-markers of MLSTP were determined according to the screening principles of Q-marker and validated the measurability.MLSTP treatment alleviated disease severity of TAO, reduced inflammatory infiltration, and ameliorated vascular function. 26 potential biomarkers associated with glutamate metabolism, linoleic acid metabolism, arachidonic acid metabolism and so on were identified. Besides, 27 prototypical components were identified in serum, 16 of which were highly correlated with efficacy and could serve as the pharmacodynamic material basis of MLSTP against TAO. In addition, 7 compounds, namely, sweroside, chlorogenic acid, calycosin-7-glucoside, formononetin, paeoniflorin, liquiritigenin and 3-butylidenephthalide, were considered as potential Q-markers of MLSTP. Ultimately, the measurability of the seven Q-markers was validated by rapid identifcation and quantifcation.This study successfully clarified the therapeutic effect and Q-markers of MLSTP by chinmedomics strategy, which is of great significance for the establishment of quality standards. Furthermore, it provides a certain reference for the screening of Q-markers in TCM prescriptions.

This article summarizes and analyzes the clinical features and gene mutation characteristics of children with noncompaction of the ventricular myocardium (NVM). For the 6 children with NVM (4 boys and 2 girls), the age of onset ranged from 3 months to 12 years. Of the 6 children, 5 had arrhythmia, 3 had cardiac insufficiency, 1 had poor mental state, and 1 had chest distress and sighing. NVM-related gene mutations were detected in 4 children, among whom 2 had MYH7 gene mutation, 1 had PRDM16 gene mutation, and 1 had mutations in the ACTN2 and TNNT2 genes. Four children had improvement in cardiac function. The two children with no significant improvement in cardiac function had a younger age of onset, a greater reduction in systolic function on echocardiography, and greater increases in myocardial enzyme and N-terminal pro-brain natriuretic peptide. It is concluded that for children with the initial symptoms of chest distress, sighing, arrhythmia, enlarged heart shadow, and increased myocardial enzyme, echocardiography and cardiac magnetic resonance are recommended for the diagnosis of NVM. NVM can have various genetic mutations.

Background Treatment of recurrent retinal detachment (re-RD) following vitrectomy (post-gas/air tamponade and post-silicone oil removal) is challenging. Previously reported treatment is commonly revision pars plana vitrectomy (PPV) combined with tamponade, which is invasive and a burden both economically and emotionally when compared with scleral buckling (SB). The purpose of this study is to report anatomical and functional outcomes of SB with or without gas tamponade in eyes with recurrent retinal detachment (re-RD) that previously underwent PPV at least once. Methods We retrospectively reviewed the medical records of 14 patients (14 eyes) who underwent PPV at least once and were treated with SB after re-RD. Preoperative characteristics, intraoperative complications, and postoperative data were assessed. The final anatomical and functional outcomes were analyzed. Results The original PPV was performed for primary rhegmatogenous retinal detachment in 11 eyes, macular hole retinal detachment in 2 eyes, and myopic foveoschisis in 1 eye. Previously, 3 eyes underwent one PPV with gas tamponade, and the remaining 11 (79%) eyes underwent 2–5 operations. Seven eyes underwent the procedure with gas injection. At the last follow-up, 13 eyes achieved total retinal attachment and 1 eye had re-RD. The postoperative intraocular pressure was within the normal range, except in 1 eye (6 mmHg). The finest postoperative best-corrected visual acuity (BCVA) was 20/25. There was a significant improvement in BCVA from 20/160 ± 20/63 at baseline to 20/80 ± 20/50 at the last visit in the 13 successfully treated eyes (P = 0.025). Conclusions SB can be effective for re-RD after PPV in specific cases.

Introduction: Cancer causes thousands of deaths worldwide each year. Therefore, monitoring of health status and the early diagnosis of cancer using noninvasive assays, such as the analysis of molecular biomarkers in urine, is essential. However, effective biomarkers for early diagnosis of cancer have not been established in many types of cancer.Areas covered: In this review, we discuss recent findings with regard to the use of urine composition as a biomarker in eleven types of cancer. We also highlight the use of urine biomarkers for improving early diagnosis.Expert opinion: Urinary biomarkers have been applied for clinical application of early diagnosis. The main limitation is a lack of integrated approaches for identification of new biomarkers in most cancer. The utilization of urinary biomarker detection will be promoted by improved detection methods and new data from different types of cancers. With the development of precision medicine, urinary biomarkers will play an increasingly important clinical role. Future early diagnosis would benefit from changes in the utilization of urinary biomarkers.

The nucleoside analogue entecavir {systematic name: 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-hydroxymethyl-2-methylenecyclopentyl]-1,9-dihydro-6H-purin-6-one}, C12H15N5O3, is an antihepatitis B virus drug that has been approved in the US, EU and several countries worldwide. We report here the single-crystal structure of the anhydrous form and compare it with that of the previously reported monohydrate form [Jiang & Liu (2009).Acta Cryst.E65, o2232]. Hirshfeld surface analysis has been employed to understand and visualize the subtle packing differences between the two crystalline forms. The results show that, compared to the previously reported hydrated form, the anhydrous crystal has significantly different intermolecular interactions and packing patterns.

The poly (N-vinyl-2-pyrrolidone)-protected AgRh nanoparticles (NPs) with various solution concentration (0.66, 1.32, 1.98 mM/L) were prepared by a simple route based on dropwise addition of KBH4 (Reducing agent). Their morphology analysis and structures were characterized by Ultraviolet-visible spectra (UV-vis), Transmission electron microscopy (TEM) and High-resolution transmission electron microscopy (HR-TEM). Femtosecond laser pulse-based single-beam Z-scan technology was employed to investigate the third-order nonlinear optical response of AgRh BNPs aqueous dispersions for the first time. As-prepared alloy-structured AgRh BNPs showed a higher third-order nonlinear optical response than Ag nanoparticles. The results indicate that the sign of nonlinear refractive index of AgRh nanoparticles is negative. The third-order nonlinear optical response of different solution concentration samples can be ascribed to the electromagnetic coupling in the near field. The fabrication of such bimetallic nanopa...

Previous studies have demonstrated that miRNAs play an important role in tumor development and progression. The role of miR-320d has been studied in several cancers except for glioma. The aim of the study was to investigate the expression levels, biological function, and mechanism of miR-320d in glioma. The expression levels of miR-320d were detected in glioma tissues and cell lines (U87 and U251) by RT-qPCR. Cell proliferation, colony formation, apoptosis, cell cycle, and transwell assays were performed in glioma cell lines transfected with miR-320d mimics or controls to evaluate the effects of miR-320d in vitro. The expression levels of invasive-related proteins were determined by Western blot analysis. Results showed that the expression of miR-320d was significantly decreased in glioma tissues and cell lines. Overexpression of miR-320d could significantly suppress cell growth, migration and invasion, and induced cell apoptosis as well as cell cycle at G0/G1 arrest in U87 and U251 cell lines. Additionally, expression levels of MMP-2, MMP-9, N-cadherin, and integrin-β1 reduced, while E-cadherin increased in miR-320d mimic group. Overall, this study is the first to demonstrate that miR-320d may serve as an independent prognostic factor, indicating that miR-320d is a biomarker for prognosis and therapy in glioma.

// Lin-Sen Yang 1, * , Xiao-Jian Zhang 2, * , Yin-Yin Xie 1 , Xiao-Jian Sun 1 , Ren Zhao 2 , Qiu-Hua Huang 1 1 State Key Laboratory of Medical Genomics, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 2 Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * These authors have contributed equally to this work Correspondence to: Ren Zhao, email: zhaoren-ruijin@hotmail.com Qiu-Hua Huang, email: hqh10632@rjh.com.cn Keywords: MAFB, SUMOylation, cell cycle, CDK6, colorectal cancer Received: July 28, 2016 Accepted: October 19, 2016 Published: November 05, 2016 ABSTRACT The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro . We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment.

The incorporation of the heterocycles into the steroid nucleus has been recognized as a useful strategy to develop new steroidal agents for disease treatment. Representative examples are abiraterone and galeterone, which are presently used in clinic for the treatment of advanced prostate cancers. Herein we have developed the first Al2O3/KF-promoted pfitzinger reactions for the synthesis of new steroidal quinolines. These new steroidal quinolines showed moderate to good antiproliferative activity against several human lung cancer cells. Of these compounds, compound 2f exhibited the best potency toward the tested three lung cancer cells with IC50 values

After construction of a dam impounding water in a reservoir, a monolithic seepage field develops in the surrounding rock mass. Here, a new finite element method is proposed for determining the shape and characteristics of the 3D monolithic seepage field including the free surface, considering complex drainage systems consisting of densely-spaced drainage holes and drainage galleries. To this end, the previously proposed virtual flux method is improved by a refined numerical integration scheme and a regularized Heaviside function for distinguishing the subregions below and above the free surface within a particular finite element. Leakage and overflow drainage holes are modeled as internal boundaries. The proposed numerical method is verified by an academic example, for which the analytical solution is available. Finally, the numerical simulation of the seepage field developing in the vicinity of a high dam and underground power house, constructed in the context of a hydropower plant project in China is used to show its application to a problem in engineering practice.

Purpose Polyphyllin VI, a main active saponin isolated from traditional medicinal plant Paris polyphylla, has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms. Methods The U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay. Cell cycle was analyzed by flow cytometry. The Polyphyllin VI-induced apoptosis was determined by Annexin V-APC/7-AAD apoptosis detection kit and JC-1 staining. Meanwhile, the autophagy was determined by acridine orange staining. The apoptosis and autophagy-related proteins were monitored by Western blot assay. Subsequently, intracellular hydrogen peroxide (H2O2) and the activation of ROS/JNK pathway were detected. Results Polyphyllin VI could potently inhibit cell proliferation by causing G2/M phase arrest. Polyphyllin VI induced mitochondria-mediated apoptosis with the upregulation of proapoptotic proteins Bax and poly ADP-ribose polymerase, and downregulation of antiapoptotic protein Bcl-2 in U2OS cells. Concomitantly, Polyphyllin VI provoked autophagy with the upregulation of critical Atg proteins and accumulation of LC3B-II. Intracellular H2O2 production was triggered upon exposure to Polyphyllin VI, which could be blocked by ROS scavenger. Polyphyllin VI dramatically promoted JNK phosphorylation, whereas it decreased the levels of phospho-p38 and ERK. Conclusion Our results reveal that Polyphyllin VI may effectively induce apoptosis and autophagy to suppress cell growth via ROS/JNK activation in U2OS cells, suggesting that Polyphyllin VI is a potential drug candidate for the treatment of osteosarcomas.

Co–Au alloy Metallic nanoparticles (MNPs) are formed by sequential ion implantation of Co and Au into silica glass at room temperature. The ion ranges of Au ions implantation process have been displayed to show the ion distribution. We have used the atomic force microscopy (AFM) and transmission electron microscopy (TEM) to investigate the formation of bimetallic nanoparticles. The extended X-ray absorption fine structure (EXAFS) has been used to study the local structural information of bimetallic nanoparticles. With the increase of Au ion implantation, the local environments of Co ions are changed enormously. Hence, three oscillations, respectively, Co–O, Co–Co and Co–Au coordination are determined.

Aims It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PM2.5) on platelet activation remains unknown, which motivates this study. Methods PM2.5 samples were collected in an urban area of Zhengzhou, China. To study the morphological characteristics and the mass concentrations of trace elements of PM2.5 samples, a filed-emission scanning electron microscope, the Image-J software, and an inductively coupled plasma mass spectrometry were used. Washed human platelets or platelet-rich-plasma were used to study the effect of PM2.5 on platelet aggregation, P-selectin expression, or platelet signaling pathways. The cytotoxicity in platelets exposed to PM2.5 was evaluated by a lactate dehydrogenase assay kit. In addition, platelet adhesion and spreading were studied on collagen-coated surfaces in stable conditions. Results The filed-emission scanning electron microscope scanning showed that PM2.5 samples varied in shape and size distributions. The mean equivalent spherical diameter of these particles was 1.97 ± 0.04 μm, of which 82.40% were particles with equivalent spherical diameters of less than 2.5 μm. The mass concentration of Ca was higher than that of other elements. The other elements followed the trend of Al>Fe>Zn>Mg>Pb>K>Mn>Cu>Ti>Ba>As>Sr>Sn>Sb>Cd>B>Se>Mo>Ag>Ni>TI>V>Co. Furthermore, pretreatment of PM2.5 significantly inhibited rather than potentiated collagen-induced platelet aggregation and P-selectin expression, whereas it had no significant effect on ADP-induced platelet aggregation and P-selectin expression. The lactate dehydrogenase analysis showed trivial cytotoxic effect of PM2.5 exposure on platelets. Pretreatment of PM2.5 inhibited platelet adhesion on immobilized collagen-coated surfaces; however, it almost did not impact the platelet spreading. Immunoblotting analysis indicated that PM2.5 reduced collagen-induced phosphorylation of phospholipase C gamma-2 (PLCγ2) at Tyr759, Akt at Ser473, and glycogen synthase kinase 3β (GSK3β) at Ser9. Conclusions PM2.5 attenuated collagen-induced platelet aggregation, α-granule secretion and adhesion, with the potential mechanism of impairing PLCγ2, Akt, and GSK3β signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75(NTR):TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.

The extended x-ray absorption fine structure (EXAFS) and the Atomic force microscopy (AFM) have been used to study the local structural information of Ni nanoparticles implanted into glass. Three different concentrations of nickel nanoparticle samples were fabricated by metal vapor vacuum arc (MEVVA) source on amorphous silicon dioxide substrate at room temperature. With the increase of Ni ion implantation, the interatomic distance and the nearest neighbor coordination number of the nearest Ni–Ni bond and Ni–O bond of nickel nanoparticle presents certain regular change.

The Ag:Al2O3 composites are prepared by Ag+ ions implantation with the acceleration voltage of 35 kV. The formation of silver nanoparticle and the surface plasma resonance (SPR) effect are studied. The appearance of absorption bands demonstrates the formation of silver nanoparticles in Al2O3. Long-time sputtering due to the high fluency removes the surface layer, and the embedded Ag NPs appear on the surface though the majorities are in the deeper area. The fluorescence spectrum of Ag:Al2O3 evaluated by Gaussian fitting consists of three peaks: 365 nm, 403 nm and 471 nm. These bands should be attributed to defects produced by the matrix and embedded Ag+ ions. In addition, a strong peak at 693 nm is supposed to be R line for Al2O3 in the emission spectrum (VUV spectrum). The crystal structure and optical properties of ion implanted sapphire have been changed after ion implantation and it is analyzed by defects and displacements. Eventually, the SRIM program is used to simulate the growth of nanoparticles with four stages.

The fluorescence effect and microstructure of the nanocomposite samples prepared by ion implantation have been studied in the subsurface area. Based on the UV-vis and VUV data, the luminescence properties of implanted samples have been presented and discussed. The research indicates that the surface plasma resonance has an impact on the fluorescence effect notably. In addition, the fluorescence performance of the substrates implanted with ions is related to the outermost electron number of the injection element. And SRIM is used to analyze the energy loss in the process of ion implantation. (C) 2015 Elsevier B.V. All rights reserved.

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by immune-mediated neuroinflammation, demyelination and neurodegeneration of the central nervous system (CNS). While matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory treatment, delayed onset and ameliorated severity of EAE, the underlying mechanisms have not been fully elucidated. In this study, we investigated the relationship between the clinical effect of MAT and the levels of certain important chemokines/chemokine receptors. Our results showed that attenuated severity of EAE resulting from MAT treatment was positively correlated with the reduction of CCL2 and CXCL10 levels in the periphery and the CNS; both of these chemokines play a crucial role in the recruitment and accumulation of inflammatory cells, especially monocytes/macrophages and T cells, into the CNS. The levels of their corresponding receptors, CCR2 and CXCR3, were also significantly reduced after MAT treatment. Taken together, our data indicate that MAT may be an effective immunomodulatory therapeutic approach for MS/EAE by countering the immune cell recruitment mechanisms.

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.

Ethnopharmacology relevance The decoction of the flowers of Abelmoschus manihot (L.) Medic was traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China for hundreds of years. Phytochemical studies have indicated that total flavonoids extracted from flowers of A. manihot (L.) Medic (TFA) were the major constituents of the flowers. Our previous studies have investigated the hepatoprotective effects of the TFA against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. This study aimed to investigate the protective effects and mechanisms of TFA on α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in rats. Material and methods The hepatoprotective activities of TFA (125, 250 and 500 mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were used as indices of hepatic cell damage and measured. Meanwhile, the serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA) were used as indices of biliary cell damage and cholestasis and evaluated. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione transferase (GST), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured in the liver homogenates. The bile flow in 4 h was estimated and the histopathology of the liver tissue was evaluated. Furthermore, the expression of transporters, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and Na+-taurocholate cotransporting polypeptide (NTCP) were studied by western blot and reverse transcription-quantitative real-time polymerase chain reaction (RT-PCR) to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results The oral administration of TFA to ANIT-treated rats could reduce the increases in serum levels of ALT, AST, LDH, ALP, GGT, TBIL, DBIL and TBA. Decreased bile flow by ANIT was restored with TFA treatment. Concurrent administration of TFA reduced the severity of polymorphonuclear neutrophil infiltration and other histological damages, which were consistent with the serological tests. Hepatic MDA and GSH contents in liver tissue were reduced, while SOD and GST activities, which had been suppressed by ANIT, were elevated in the groups pretreated with TFA. With TFA intervention, levels of TNF-α and NO in liver were decreased. Additionally, TFA was found to increase the expression of liver BSEP, MRP2, and NTCP in both protein and mRNA levels in ANIT-induced liver injury with cholestasis. Conclusion TFA exerted protective effects against ANIT-induced liver injury. The possible mechanisms could be related to anti-oxidative damage, anti-inflammation and regulating the expression of hepatic transporters. It layed the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effects of A. manihot (L.) Medic for the treatment of jaundice.

Because of the complicated chemical composition of Traditional Chinese Medicines, their chemical profile study has been a great challenge. In the present work, a homologues prediction strategy for rapid screening and identification of C

The single crystal alumina was fabricated by the Czochralski method. The copper ions were doped into the alumina sample to form the Cu:Al2O3 composite material. The doping energy is 35 keV and the ion concentration is 1.2×1017 ions/cm2. The suppercontinuum spectrum was investigated to show the larger nonlinear refraction of this composite material. The nonlinear optical refractive property of the Cu:Al2O3 composite material was investigated by using the Kerr-lens autocorrelation technique for the first time. The nonlinear optical refractive indices, n2=2.8×10−15 cm2/W at 800 nm, is larger than the value of the single crystal alumina. The mechanism of the nonlinear optical refraction has been discussed and it is due to the optical Kerr effect.

Ethnopharmacological relevance Suanzaorenhehuan Formula (SHF) has been used for treating depression-like disorders for many years in China. The saponins part of the SHF (SSHF) extract was the antidepressant effective component. Aim of study To investigate the antidepressant-like effect of SSHF and its possible mechanisms. Materials and methods Experimental approaches including the forced swim test (FST), the tail suspension test (TST) and unpredictable chronic mild stress (UCMS) were used to evaluate the effects of SSHF. The possible mechanisms were explored by measuring monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme (MAO) activities, antioxidant enzyme activities and free radicals levels in the brains of UCMS-exposed mice. Results The results showed that SSHF (10, 20, 40 mg/kg) significantly decreased the immobility period in FST and TST in mice after two-week treatment. Whereas, SSHF had no significant effect on locomotor activity in mice. It was also found that the serotonin (5-HT) and noradrenaline (NE) levels in the hippocampus and frontal cortex were significantly increased only in 40 mg/kg SSHF treated mice. In addition, SSHF (10, 20, 40 mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day UCMS exposure. SSHF (10, 20, 40 mg/kg) significantly decreased the nitrous oxide (NO) levels, and increased the activities of total antioxidant capability (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) in different degrees in the brains of UCMS-exposed mice. Conclusions Our results suggested that SSHF may effectively produce an antidepressant-like effect, which appeared to involve the serotonergic, noradrenergic, monoamine oxidase enzyme and antioxidant systems.

It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PMPMThe filed-emission scanning electron microscope scanning showed that PMPM

Cracking of the cover concrete due to steel corrosion is considered as one of the major issues of durability of reinforced concrete (RC) structures. Numerous models have been developed to predict the time from corrosion initiation to cracking of the cover concrete. However, little work has been done on the effects of stirrup on reinforcement corrosion-induced cover cracking. In this paper, the effects of stirrup on reinforcement corrosion-induced cover cracking are investigated. The results of four short columns (section size 100×100 mm, total length 515 mm) subjected to accelerated corrosion clearly show that stirrups not only can effectively postpone and prevent the longitudinal crack initiation but also can restrict the width of cracks caused by corrosion of reinforcement. Therefore, prediction models should account for the effects of stirrup on reinforcement corrosion-induced cover cracking, and even the effects of load on it.

A rapid indirect competitive ELISA (icELISA) format has been developed for the determination of enrofloxacin (ENR) residues in chicken. For this purpose, carbodiimide active ester method was employed to synthesize the artificial antigen of ENR-BSA, and anti- serum produced from the immunized rabbits was tested by indirect ELISA and icELISA. By the square matrix titration, the icELISA method was developed for the quantitative detection of ENR, based on the pAb. The Linear range was from 0.006 to 31.5 ng/mL, with LOD and IC50 value of 0.003 ng/mL and 0.45 ng/mL, respectively. Except for a high cross-reactivity (105.2%) to Ciprofloxacin, negligible cross-reactivity to the other compounds was observed. The recoveries of ENR were in the range of 98.3-127.5%, 85.7-112.5% and 97.4-103.8% for chicken muscle, liver and kidney, respectively. After optimization, 0.03 mol/L of HCl was used in the assay buffer and this ELISA system can tolerate acetonitrile not higher than 10%. The correlation coefficients (R2) of the ELISA and LC-MS data were 0.9472 in muscle, 0.9843 in liver, and 0.9382 in kidney. Therefore, this assay has the potential to be incorporated into a quantitative monitoring program for the rapid screening of ENR residue in food.

We introduce the high smart pressure sensor’s hardware-circuit design which based on Ultra-Low Power MSP430 MCU, analyze the BP network algorithm in temperature compensation to deal with the pressure sensor’s temperature drift, and collect pressure sensor’s temperature and pressure signals by MCU for offline training in BP network. The result shows that the MSP430 MCU can reduce system power and its rich exterior equipments can reduce the size of pressure sensor, the accuracy is improved by BP network algorithm, zero drift and time drift are best controlled.