Improved Performance of All-Inorganic Perovskite Light-emitting Diodes via Nanostructured Stamp Imprinting.

Halide perovskites are emerging emitters with excellent optoelectronic properties. Contrary to the large grain fabrication goal in perovskite solar cells, perovskite light-emitting diodes (PeLEDs) based on small grain enable efficient radiative recombination because of relatively higher charge carrier densities due to spatial confinement. However, achieving small-sized grain growth with superior crystal quality and film morphology remains a challenge. In this work, we demonstrated a nanostructured stamp thermal imprinting strategy to boost the surface coverage and improve the crystalline quality of CsPbBr3 film, particularly confine the grain size, leading to the improvement of luminance and efficiency of PeLEDs. We improved the thermal imprinting process utilizing the nanostructured stamp to selectively manipulate the nucleation and growth in the nanoscale region and acquire small-sized grain accompanied by improved crystal quality and surface morphology of the film. By optimizing the imprinting pressure and the period of the nanostructures, appropriate grain size, high surface coverage, small surface roughness and improved crystallization could be achieved synchronously. Finally, the maximum luminance and efficiency of PeLEDs achieved by nanostructured stamp imprinting with a period of 320 nm are 67600 cd/m2 and 16.36 cd/A, respectively. This corresponds to improvements of 123 % in luminance and 100 % in efficiency, compared to that of PeLEDs without the imprinting.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Trifluoromethylation of dihydrocoptisines and the effect on structural stability and XBP1-activating activity.

In order to obtain new dihydrocoptisine-type compounds with stable structure and activating XBP1 transcriptional activity, (±)-8-trifluoromethyldihydrocoptisine derivatives as target compounds were synthesized from quaternary ammonium chlorides of coptisine alkaloids as starting materials by a one-step reaction. The structures of the synthesized compounds were confirmed by 1H-, 13C-, and 19F-NMR as well as HRESIMS methods. These compounds showed more significant structural stability and activating XBP1 transcription activity in vitro than dihydrocoptisine as positive control. No obvious cytotoxicity on normal cell in vitro was observed with (±)-8-trifluoromethyldihydrocoptisines. Trifluoromethylation can be used as one of the fluorine modification strategies for dihydrocoptisines to guide follow-up studies on structural modification of coptisine-type alkaloids and on anti-Ulcerative colitis drugs with coptisines.

Syntheses and Structure-Activity Relationships in Antibacterial Activity against Clostridium difficile and XBP1 Activation Property of 13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines.

13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines were synthesized to evaluate antibacterial activity against Clostridium difficile and activating x-box-binding protein 1 (XBP1) activity, biological properties both associated with ulcerative colitis. Improving structural stability and ameliorating biological activity were major concerns. Different substituents on the structural modification site were involved to explore the influence of diverse structures on the bioactivities. The target compounds exhibited the desired activities with definite structure-activity relationship. In the series of 13-[(N-n-alkylamino)methyl]-8-oxodihydrocoptisines, the length of n-alkyl groups has a definite effect on the bioactivity, elongation of the length increasing the antibacterial activity. The synthesized compounds were determined to display strong or weak XBP1-activating activity in vitro. The preliminary results of this study warrant further medicinal chemistry studies on these synthesized compounds.

[Research development on modern pharmacological effect of tetrandrine].

Han stephania, also known as Stephania tetrandra, expelling wind, relieve pain and inducing diuresis for removing edema, is a traditional Chinese medicine for treating rheumatic arthralgia. Alkaloids have an important pharmacodynamic basis in S. tetrandra, and tetrandrine is one kind content of bisbenzylisoquinoline alkaloids, which has many biological activities. These activities include anti-tumor in many ways, clinically inhibiting multiple inflammatory factors, preventing and treating liver fibrosis and renal fibrosis and many other kinds of fibrotic diseases, and in addition, tetrandrine could work synergistically with other drugs. In recent years, through in-depth research by scholars at home and abroad, it has been found that tetrandrine has a protective effect on the nervous system and ischemia-reperfusion injury. At the same time, as a calcium ion antagonist, tetrandrine could effectively block the deposition of calcium ions inside and outside the cell. In summary, the application prospect of tetrandrine in clinical practice is very extensive. In this paper, the pharmacological effects of tetrandrine and the possible mechanisms for these effects are summarized, and review its current research progress. It is hoped that the possible application direction of tetrandrine can be revealed more comprehensively, and provide better enlightenment and ideas for clinical application.

Syntheses and structure-activity relationships on antibacterial and anti-ulcerative colitis properties of quaternary 13-substituted palmatines and 8-oxo-13-substituted dihydropalmatines.

In this study, quaternary palmatine is used as a lead compound to design and synthesize derivatives to evaluate bioactivities, with twenty-seven compounds of four series being obtained. Antibacterial activity was examined by determining the minimal inhibitory concentration (MIC) values on Staphylococcus aureus, Escherichia coli, and Candida albicans, three series of derivatives being found to exhibit activity in vitro with significant structure-activity relationship (SAR). Elongating the carbon chain led to the antibacterial activity increased, with quaternary 13-hexanoylpalmatine chloride, quaternary 13-(ω-ethoxycarbonyl)heptylpalmatine chloride, and 8-oxo-13-(N-n-nonyl)aminomethyldihydropalmatine, all of which possess the longest aliphatic carbon chain in the corresponding series of derivatives, showing the MIC values of 62.5, 7.81, and 15.63 µg/ml against S. aureus, respectively. The property of anti-ulcerative colitis (anti-UC) was assessed at the levels of both in vitro and in vivo, with X-box-binding protein 1 (XBP1) being targeted in vitro. Seven compounds were found not only to be hypocytotoxic toward intestinal epithelial cells, but also to exhibit activity of activating the transcription of XBP1 in vitro. Five compounds were found to possess significant dose-effect relationship with EC50 values at a level of 10-7 µM in vitro. 8-Oxo-13-formyldihydropalmatine as an intermediate was found to display significant curative effect on UC in vivo based on the biomarkers of body weight change, colon length change, and calculated values of disease activity index and colon macroscopic damage index of the experimental animals, as well as the examination into the pathological changes of the colon tissue of the modeled animals.

MicroRNA-98 regulates osteogenic differentiation of human bone mesenchymal stromal cells by targeting BMP2.

To study the effects of microRNA-98 (miR-98) on human bone mesenchymal stromal cells (hBMSCs). The patients undergoing hip arthroplasty were selected by inclusion/exclusion criteria for this study. The extracted hBMSCs were detected of osteogenic differentiation by alizarin red S staining, and of cell phenotype by flow cytometry. Bioinformatics, dual luciferase report, western blotting, RT-PCR and immunoblotting were used in our study. The hBMSCs were divided into miR-98 mimics, miR-98 negative control (NC), miR-98 inhibitors, Mock and miR-98 inhibitors + siBMP2 groups. Human bone mesenchymal stromal cells were extracted and purified in vitro and had specific cytological morphology, surface markers and abilities of self-renewal and differentiation. Compared with the NC group and Mock group, the miR-98 mimics group showed increased miR-98 level while the miR-98 inhibitors group decreased miR-98 level (both P < 0.01). Dual luciferase reporter showed BMP2 was the target gene of miR-98. The levels of mRNA and protein expression of BMP2, protein expression of RUNX2, alkaline phosphatase activity and osteocalcin content significantly decreased in the miR-98 mimics group while increased in the miR-98 inhibitors group and showed no changes in the NC group and Mock group (all P < 0.05). The miR-98 mimics group showed obviously declined stained red particles and the miR-98 inhibitors group showed opposite result. After lowering the expression of miR-98, osteogenic differentiation ability of hBMSCs rose, which was weakened by the transfection with siBMP2. miR-98 may regulate osteogenic differentiation of hBMSCs by targeting BMP2.

Azacyclo-indoles and Phenolics from the Flowers of Juglans regia.

Seven new azacyclo-indoles and phenolics and four known alkaloids were isolated from the flowers of Juglans regia. Spectroscopic and chromatographic data revealed that the structures of the new compounds are 5,6,11,12-tetrahydropyrrolo[1',2':1,2]azepino[4,5-b]indole-3-carbaldehyde (1), (±)-5,6,7,11c-tetrahydro-1H-indolizino[7,8-b]indol-3(2H)-one (2), (±)-9-hydroxy-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-2-carboxamide (3), 5-(ethoxymethyl)-1-(4-hydroxyphenethyl)-1H-pyrrole-2-carbaldehyde (4), (±)-5,8-dihydroxy-4-(1H-indol-3-yl)-3,4-dihydronaphthalen-1(2H)-one (5), (±)-4-(6-amino-9H-purin-9-yl)-5,8-dihydroxy-3,4-dihydronaphthalen-1(2H)-one (6), and (±)-4-(6-amino-9H-purin-9-yl)-5-hydroxy-3,4-dihydronaphthalen-1(2H)-one (7). The five pairs of enantiomers were resolved, and the absolute configurations of the enantiomers were assigned via electronic circular dichroism data. Compound 1 exhibited significant in vitro growth inhibition against the HCT-116, HepG2, BGC-823, NCI-H1650, and A2780 cancer cell lines, with IC50 values of 2.87, 1.87, 2.28, 2.86, and 0.96 µM, respectively, and low cytotoxicity toward normal IEC-6 cells, with a 79.6% survival rate at a 10 µM concentration.

[Studies on chemical constituents of Clinopodium chinense].

Twenty-eight compounds were isolated and purified from Clinopodium chinense by Sephedax LH-20, ODS, MCI and preparative HPLC. Their structures were identified as apigenin (1), apigenin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucuronopyranoside (3), thellungianol (4), apigenin-7-O-ß-D-rutinoside (5), luteolin (6), luteolin-4'-O-ß-D-glucopyranoside (7), apigenin-7-O-ß-D-pyranglycuronate butyl ester (8), luteolin-7-O-ß-D-rutinoside (9), luteolin-7-O-ß-D-noehesperidoside (10), acacetin (11), acacetin-7-O-ß-D-glucuronopyranoside (12), buddleoside (13), naringenin (14), pruning (15), nairutin (16), isosakuranetin (17), isosakuranin (18), didymin (19), hesperidin (20), kaempferol (21), quercetin (22), kaempferol-3-O-α-L-rahmnoside (23), p-hydroxycinnamic acid (24), caffeic acid (25), cis-3-[2-[1-(3,4-dihydroxy-phenyl)-1 -hydroxymethyl]-1,3-ben-zodioxol-5-yl]-(E)-2-propenoic acid (26), mesaconic acid (27), gentisic acid 5-O-ß-D-(6'-salicylyl)-glucopyranoside (28). Among them, compounds 7, 9-10, 12, 23, 26-28 were isolated from the Clinopodium for the first time. The protective effects of compounds 1-6, 8-17 and 19 against H2O2-induced H9c2 cardiomyocyte injury were tested, compounds 15 exhibited significantly protective effects. Compared with the cell viability of (62.12±6.18)% in the model, pruning exhibited viabilities of (84.25±7.36)% at 25.0 mg•L⁻¹, respectively, using quercetin as a positive control [cell viability of (84.55±8.26)%, 20 mg•L⁻¹].

Synthesis and Structure-Activity Relationships of N-Dihydrocoptisine-8-ylidene Aromatic Amines and N-Dihydrocoptisine-8-ylidene Aliphatic Amides as Antiulcerative Colitis Agents Targeting XBP1.

In this study, natural quaternary coptisine was used as a lead compound to design and synthesize structurally stable and actively potent coptisine analogues. Of the synthesized library, 13 N-dihydrocoptisine-8-ylidene amines/amides were found not only to be noncytotoxic toward intestinal epithelial cells (IECs), but they were also able to activate the transcription of X-box-binding protein 1 (XBP1) targets to varying extents in vitro. Antiulcerative colitis (UC) activity levels were assessed at the in vitro molecular level as well as in vivo in animals using multiple biomarkers as indices. In an in vitro XBP1 transcriptional activity assay, four compounds demonstrated good dose-effect relationships with EC50 values of 0.0708-0.0132 µM. Moreover, two compounds were confirmed to be more potent in vivo than a positive control, demonstrating a curative effect for UC in experimental animals. Thus, the findings of this study suggest that these coptisine analogues are promising candidates for the development of anti-UC drugs.

Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents.

Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 µM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.

Cembranoids from the Gum Resin of Boswellia carterii as Potential Antiulcerative Colitis Agents.

Eight new cembranoids, boscartins A-H (1, 2, and 4-9), and the known incensole oxide were isolated from the gum resin of Boswellia carterii. The absolute configurations of 1, 2, 4, and incensole oxide were unequivocally resolved using single-crystal X-ray diffraction analysis with Cu Kα radiation, and the absolute configuration of 5 was resolved via electronic circular dichroism data. The antiulcerative colitis activities of the compounds were evaluated in an in vitro x-box-binding protein 1 (XBP 1) transcriptional activity assay using dual luciferase reporter detection. At 10 µM, compounds 1, 5, 6, and 7 significantly activated XBP 1 transcription with EC50 values of 0.34, 1.14, 0.88, and 0.42 µM, respectively, compared with the pGL3-basic vector control.

[Chemical constituents of the roots of Macleaya microcarpa and activation efficacy of benzophenanthridine alkaloids for the transcription of xbp1 gene].

Ongoing study on the chemical constituents of the roots of Macleaya microcarpa led to the isolation of eight compounds of derivatives of triterpenes and organic acids in addition to some previously identified benzophenanthridines. The eight compounds were identified by spectroscopic methods as well as comparison with literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen-30-oic acid (2), 3α-hydroxy-12-oleanen-30-oic acid (3), 3ß-hydroxy-12-oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-ß-D-glucoside (6), 3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first time. In order to discover natural active compounds as potential agents of anti-ulcerative colitis (UC), an in vitro drug high-throughput screening model targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of the major chemical constituents of M microcarpa. The result confirmed that two dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine (10), showed a certain activity on activating the transcription of xbpl, a transcription factor (TF) associated with the occurrence, development, and potential treatment of UC, with their relative activating ratios being 1.76 and 1.77 times, respectively, as compared with control group.

[Constituents with anti-oxidative activity from seeds of Jufeng grape].

Taking application of some isolation and purification technologies, including crushing, solvent extraction, preliminary solvent isolation, column chromatographies over silica gel and Sephadex LH-20 gel and preparative HPLC, 8 compounds were obtained from the seeds of Jufeng grape sourced from market. Their structures were identified by spectroscopic methods and comparison with literature values as Catechin (1), Epicatechin (2), quercetin (3), ethylgallate (4), rel-(2S, 3R) -2-(4-hydroxy-3-methoxyphenyl) -3- (hydroxymethyl)-5-(3-hydroxypropyl)-2,3-dihydrobenzofuran-7-ol (5), rel-(2α, 3ß)-7-O-methylcedrusin (6), rel-(1R,2S)-1-(4-hydroxy-3-methoxyphenyl) -2-(4-(3-hydroxypropyl) -2-methoxyphenoxy) propane-1,3-diol (7), and (+) -isolariciresinol (8), respectively. Compounds 5-8 were serial lignans isolated from the seeds of grape for the first time. Structurally, 5 and 6 belong in benzofuran-8,3'-neolignans, 7 in 8,4'-oxyneolignan, and 8 in 8,8' :2,7'-cyclolignan. According to in vitro activity evaluation conducted in cell model, compound 6 showed significant anti-oxidative ability, with the activity of RAW264. 7 cell superoxide dismutase being raised evidently in the test as compared with the positive anti-oxidative agents, compounds 1 and 2.

The inhibition effect and mechanism of SY0916 on pulmonary fibrosis.

SY0916 is a new platelet-activating factor receptor antagonist developed by our institute. In this study, the inhibitory effect of SY0916 on pulmonary fibrosis was investigated in epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-ß1) in vitro and a pulmonary fibrosis animal model induced by bleomycin (BLM). The results showed that SY0916 could inhibit the EMT of A549 cells induced with TGF-ß1. In vivo, SY0916 administration significantly ameliorated the BLM-mediated histological changes, reduced main biochemical parameters related to pulmonary fibrosis such as hydroxyproline and glutathione, and also notably attenuated the expression of key pro-fibrotic mediator, TGF-ß1. These findings demonstrated that SY0916 could possibly be developed as a promising candidate for the treatment of pulmonary fibrosis.

New synthetic method of 8-oxocoptisine starting from natural quaternary coptisine as anti-ulcerative colitis agent.

Quaternary coptisine (1), a natural bioactive quaternary protoberberine alkaloid (QPA), was treated with potassium ferricyanide in aqueous solution of 5 N sodium hydroxide leading to the acquisition of 8-oxocoptisine (2) with much higher yield than reported in the literature. This is the first report of the oxidation of a natural QPA by applying potassium ferricyanide as an oxidant. 8-Oxocoptisine showed significant anti-ulcerative colitis efficacy in vitro with EC50 value being 8.12 × 10(- 8) M.

[Effect of a novel selective S1P1 agonist, Syl948, on mouse skin transplantation].

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.

[Mechanism about therapeutic effect of meisoindigo on psoriasis via down-regulation of the TLR4-TAK-NF-kappaB pathways].

Meisoindigo is an indigo natural derivative commonly used in anti-cancer therapy. In the clinical application, it was also found to have good therapeutic effect on psoriasis. In order to further understand its mechanism of action, human normal keratinocyte cell line HaCaT and RAW 264.7 were used to identify if meisoindigo could affect the inflammatory factors such as NO and other important cytokines which were highly involved in psoriasis. Our results indicated that meisoindigo decreased the production of NO in LPS-stimulated RAW 264.7 cells and reduced the expression of cytokines in LPS-stimulated HaCaT cells. And TLR4-TAK-NF-kappaB was a possible pathway mainly involved in the attenuation of iNOS and pro-inflammatory cytokine production by meisoindigo, which may take part in the therapeutic effect of meisoindigo on psoriasis.

[Determination of 12 typical personal care products in human urine samples by ultra performance liquid chromatography-tandem mass spectrometry].

A rapid and sensitive method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 12 typical personal care products (PCPs) in human urine. These PCPs included five paraben preservatives (PBs), five benzophenone UV absorbers (BPs), and two antibacterial agents. Accordingly, 1 mL of the urine sample was mixed with 500 µL of ß-glucuronidase-ammonium acetate buffer solution (enzymatic activities are 500 units/mL) and 75 µL of a mixed internal standard working solution (internal standard contents are 7.5 ng), followed by enzymatic hydrolysis overnight (≥16 h) at 37 ℃ in a water bath. The 12 targeted analytes were enriched and cleaned up using an Oasis HLB solid phase extraction column. Separation was performed on an Acquity BEH C18 column (100 mm×2.1 mm, 1.7 µm) using an acetonitrile-water system as the mobile phase, in negative electrospray ionization (ESI-) multiple reaction monitoring (MRM) mode, for target detection and stable isotope internal standard quantification. The optimal MS conditions were established by optimizing the instrument parameters and comparing two analytical columns (Acquity BEH C18 and Acquity UPLC HSS T3) as well as different types of mobile phases (methanol or acetonitrile as the organic phase) to achieve better chromatographic separation. In order to obtain higher enzymatic and extraction efficiency, different enzymatic conditions, solid phase extraction columns, and elution conditions were investigated. The final results showed that methyl parabens (MeP), benzophenone-3 (BP-3), and triclosan (TCS) showed good linearities in the ranges of 4.00-800, 4.00-800 and 5.00-200 µg/L, respectively, the other targeted compounds showed good linearities in the ranges of 1.00-200 µg/L. The correlation coefficients were all greater than 0.999. The method detection limits (MDLs) were in the range of 0.06-1.09 µg/L, and the method quantification limits (MQLs) ranged from 0.08 to 3.63 µg/L. At three spiked levels, the average recoveries of the 12 targeted analytes ranged from 89.5% to 111.8%. The intra-day and inter-day precisions were 3.7%-8.9% and 2.0%-10.6%, respectively. The results of the matrix effect assessment showed that MeP, ethyl paraben (EtP), and benzophenone-2 (BP-2) exhibited strong matrix effects (26.7%-103.8%); propyl paraben (PrP) exhibited moderate matrix effects (79.2%-112.0%); and the other eight target analytes exhibited weak matrix effects (83.3%-113.8%). The matrix effects of the 12 targeted analytes after correction using the stable isotopic internal standard method ranged from 91.9% to 110.1%. The developed method was successfully applied to the determination of the 12 PCPs in 127 urine samples. Ten typical PCPs were detected, with the overall detection rates ranging from 1.7% to 99.7%, except for benzyl paraben (BzP) and benzophenone-8 (BP-8). The results revealed that the population in this area was widely exposed to PCPs, especially MeP, EtP and PrP; the detection rates and concentrations of these PCPs were found to be very high. Our analytical method is simple and sensitive, and it is expected to be an effective tool for biomonitoring PCPs in human urine samples as part of environmental health studies.

[Immunosuppressive effect of S1P1 receptor agonist FTY720].

FTY720 is a synthetic compound derived from the metabolites of Isaria sinclairii. Its unique chemical structure and mechanism appear to be distinctive from other known immunosuppressors. In the present study, the effect of FTY720 on immunosuppression and toxicity to heart was evaluated by detection of lymphocytes count, heart rate in rats, the survival time of the allografts of skin slice in mice and binding to S1P1 and S1P3 receptors by confocal. The results showed that FTY720 could induce lymphopenia, reduce the heart rates in rats and prolong the survival time of the allografts of skin slice in mice. The assay results on confocal showed that FTY720 can bind with S1P1 and S1P3 on surface of CHO-S1P1 and CHO-S1P3 cells. FTY720 could be developed for wide application for organ transplantation and self-immunity diseases.