Rapid Determination of Bucinnazine in Blood by UPLC-MS/MS.

OBJECTIVES: To establish a rapid method for the analysis of bucinnazine in blood by UPLC-MS/MS and to apply the method to the practical case. METHODS: After the internal standard was added to blood, the protein was precipitated with 900 µL mixed solution (Vacetonitrile∶Vwater=8∶2). After vortex and centrifugation, the protein was measured through 0.22 µm filter membrane. The separation was performed on C18 chromatography column, with acetonitrile and 5 mmol/L ammonium acetate containing 0.1% formic acid aqueous as mobile phase gradient elution at the flow rate of 0.4 mL/min. Multiple reaction monitoring scan was performed in electrospray positive ion mode, quantitative measurement was performed by internal standard method, and methodological verification was carried out. RESULTS: The linear relationship of bucinnazine in blood was good in the range of 0.5-200 µg/L, the correlation coefficient (r) was 0.999 7, the limit of detection was 0.1 µg/L, the limit of quantitation was 0.5 µg/L, and the recovery was 78.3%-83.8% at 1, 10 and 100 µg/L mass concentration levels. The matrix effect was 69.4%-73.8%, the intra-day precision was 1.9%-2.8%, and the inter-day precision was 2.8%-3.2%, the accuracy was 3.1%-3.5%. The stability test results of 1 and 100 µg/L mass concentrations at -25 ℃ showed that the accuracy (bias) of 10 d was less than 4.5%. CONCLUSIONS: This method has the advantages of simple pre-treatment process, fast sample processing speed, high sensitivity of instrument analysis, good stability of content determination and reliable identification results, and can meet the needs of case identification.

A novel monospecific tetravalent IgG1-(scFv)2 version shown enhanced neutralizing and Fc-mediated effector functions against SARS-CoV-2.

Neutralizing monoclonal antibodies (nMABs) have been proved to be effective therapeutics in treating coronavirus disease (COVID-19). To enhance the potency of nMAB 553-15, we generated a novel monospecific tetravalent IgG1-(scFv)2 version. This was achieved by covalently fusing two forms of 553-15-derived single chain variable fragments (scFv) to the C-terminus of the hIgG1 (human Immunoglobulin G1) Fc fragment. We found that the Fc-fused VL-linker-VH format achieved similar binding affinity and neutralizing behavior as 553-15. The tetravalent versions were constructed by fusing the scFv domains to the C-terminus of nMAB 553-15. As a result, the tetravalent version 55,315-VLVH exhibited significantly higher binding activity to target spike protein variants and enhanced neutralization against VOCs (variants of concern) pseudovirus compared to 553-15. We also measured the Fc effector responses of candidates using wild-type Spike-expressing CHOK1 cells. The 55,315-VLVH enhanced the function of ADCP (antibody-dependent cellular phagocytosis) but had similar IL-6 release levels compared to the bivalent 553-15. It seemed that the novel tetravalent version avoids the pro-inflammatory effect induced by macrophage activation. However, the 55,315-VLVH displayed slightly increased potency in ADCC (antibody-dependent cell-mediated cytotoxicity) and CDC (complement-dependent cytotoxicity), which might contribute to higher systemic inflammation. Further investigation is necessary to determine whether the tetravalent version is beneficial to balance efficiency and safety against COVID-19.

Development of the Novel Bifunctional Fusion Protein BR102 That Simultaneously Targets PD-L1 and TGF-ß for Anticancer Immunotherapy.

Immune checkpoint inhibitors (ICIs) are remarkable breakthroughs in treating various types of cancer, but many patients still do not derive long-term clinical benefits. Increasing evidence shows that TGF-ß can promote cancer progression and confer resistance to ICI therapies. Consequently, dual blocking of TGF-ß and immune checkpoint may provide an effective approach to enhance the effectiveness of ICI therapies. Here, we reported the development and preclinical characterization of a novel bifunctional anti-PD-L1/TGF-ß fusion protein, BR102. BR102 comprises an anti-PD-L1 antibody fused to the extracellular domain (ECD) of human TGF-ßRII. BR102 is capable of simultaneously binding to TGF-ß and PD-L1. Incorporating TGF-ßRII into BR102 does not alter the PD-L1 blocking activity of BR102. In vitro characterization further demonstrated that BR102 could disrupt TGF-ß-induced signaling. Moreover, BR102 significantly inhibits tumor growth in vivo and exerts a superior antitumor effect compared to anti-PD-L1. Administration of BR102 to cynomolgus monkeys is well-tolerated, with only minimal to moderate and reversing red cell changes noted. The data demonstrated the efficacy and safety of the novel anti-PD-L1/TGF-ß fusion protein and supported the further clinical development of BR102 for anticancer therapy.

Optimization strategies for expression of a novel bifunctional anti-PD-L1/TGFBR2-ECD fusion protein.

The novel anti-PD-L1/TGFBR2-ECD fusion protein (BR102) comprises an anti-PD-L1 antibody (HS636) which is fused at the C terminus of the heavy chain to a TGF-ß1 receptor Ⅱ ectodomain (TGFBR2-ECD), and which can sequester the PD-1/PD-L1 pathway and TGF-ß bioactivity in the immunosuppressive tumor microenvironment. In the expression of TGFBR2-ECD wild-type fused protein (BR102-WT), a 50 kDa clipped species was confirmed to be induced by proteolytic cleavage at a "QKS" site located in the N-terminus of the ectodomain, which resulted in the formation of IgG-like clipping. The matrix metalloproteinase-9 was determined to be associated with BR102-WT digestion. In addition, it was observed that the N-glycosylation modifications of the fusion protein were tightly involved in regulating proteolytic activity and the levels of cleavage could be significantly suppressed by MMP-inhibitors. To avoid proteolytic degradation, eliminating protease-sensitive amino acid motifs and introducing potential glycosylation were performed. Three sensitive motifs were mutated, and the levels of clipping were strongly restrained. The mutant candidates exhibited similar binding affinities to hPD-L1 and hTGF-ß1 as well as highly purified BR102-WT2. Furthermore, the mutants displayed more significant proteolytic resistance than that of BR102-WT2 in the lysate incubation reaction and the plasma stability test. Moreover, the bifunctional candidate Mu3 showed an additive antitumor effect in MC38/hPD-L1 bearing models as compared to that of with anti-PD-L1 antibody alone. In conclusion, in this study, the protease-sensitive features of BR102-WT were well characterized and efficient optimization was performed. The candidate BR102-Mutants exhibited advanced druggability in drug stability and displayed desirable antitumor activity.

High-Temperature Molecular Ferroelectric Tris(2-hydroxyethyl) Ammonium Bromide with Dielectric Relaxation.

We obtained one new molecular ferroelectric material tris(2-hydroxyethyl) ammonium bromide (TAB) that crystallizes in aqueous solution at room temperature with a space group of R3m which belongs to ten polar space groups. There is a paraelectric-to-ferroelectric phase transition at 424 K (from hexagonal R3̅m to hexagonal R3m phase). Such a high transition temperature is close to that of diisopropylamine bromide (426 K) and higher than that of many other molecular ferroelectrics, such as triethylmethylammonium tetrabromoferrate(III) (360 K); some of the organic-inorganic perovskite ferroelectrics, such as (cyclohexylammonium)2PbBr4 (363 K); and some inorganic ferroelectrics, including BaTiO3 (393 K). The saturated polarization and the coercive field of TAB measured from the ferroelectric hysteresis loop are about 0.54 µC·cm-2 and 0.62 kV/cm, respectively. Given its superior performance, including high phase transition temperature, room-temperature ferroelectricity, small coercive electric field, and adjustable ladder-shaped dielectric constant, TAB will have many potential applications.

Ferroelectricity of the Orthorhombic and Tetragonal MAPbBr3 Single Crystal.

Hybrid organic-inorganic halide perovskites (HOIPs) MAPbBr3 and their ramifications have emerged because of the photovoltaic, optical, and other fascinating performances of HOIPs in recent years. However, many intrinsic properties, such as crystal structure and ferroelectricity, are still controversial. In this work, the ferroelectricity of the orthorhombic and tetragonal MAPbBr3 single crystal was confirmed through the dielectric behavior versus bias electric field ε( E), the temperature-dependent pyroelectric current with positive/negative poling, and the positive-up-negative-down (PUND) measurements. The electric field dependence of dielectric constant curves shows a butterfly type shape in the orthorhombic and tetragonal phase. The pyroelectric current shows two maxima at 155 and 245 K, corresponding to ferroelectric-ferroelectric and ferroelectric-paraelectric phase transitions, respectively. In particular, the direction of the pyroelectric current can be reversed by a positive or negative poling electric field, which is the assertive evidence of ferroelectricity. The PUND measurements act as the most convincing proof of the ferroelectricity of the MAPbBr3 single crystal. This work reports new evidence of the ferroelectric properties of the MAPbBr3 single crystal, which provides the intrinsic property when considering their high power conversion efficiencies.

Preliminary investigation of the effects of an FCF inhibitor interference with Septin in the early stage embryos in mice.

The objective of the present study was to investigate the effects of for chlorfenuron (FCF) interference with the septin protein on early stage embryos in mice. The 1­cell embryos were collected and divided into an FCF interference group and a control group. The FCF interference group was cultured in FCF media and the control group was cultured in dimethyl sulphoxide media at 37˚C with 5% CO2 until the desired phase was achieved. Septin2 protein expression was detected using immunofluorescence and western blot analysis. Blastocyst α­tubulin was stained by immunofluorescence to observe the alterations in spindles and microtubules. The rate of early embryo development into blastocysts was significantly reduced following FCF treatment (P<0.05). In the control group, septin2 was observed with a confocal microscope; septin2 was expressed in embryos at all stages and mainly in the blastomeres from the 2­cell stage onwards, with the expression concentrated in the nuclei of the blastomeres as identified by strong fluorescence. In the FCF interference group, septin2 was weakly expressed in the nuclei of blastomeres at the 2­ and 4­cell stages, and in the granulated blastomeres at the 4­ and 8­cell stages. Expression was barely observed in and following the morula. Granulation was observed starting from the 4­ and 8­cell stages. Compared with the control group, the FCF interference group exhibited irregular microtubules, abnormal spindle morphology and disordered chromosome arrangement in the blastocysts. The septin2 protein was expressed throughout the early stage embryo from the 2­cell stage to the blastocyst and localized in the nuclei of blastomeres. When the septin protein experienced interference by the FCF inhibitor, septin2 protein expression was reduced, which simultaneously resulted in abnormal embryonic development, uneven cytoplasmic division, various sizes and a reduced number of blastomeres, granulation in the blastomeres, disordered blastocyst microtubule distribution, spindle shape alterations and an abnormality of chromosome arrangement.

Efficacy of weight adjusted bone mineral content in osteoporosis diagnosis in Chinese female population / 中华医学杂志(英文版)

BACKGROUND@#Areal bone mineral density (aBMD) applied for osteoporosis diagnosis unavoidably results in the missingdiagnosis in patients with large bones and misdiagnosis in those with small bones. Therefore, we try to find a new adjusted index of bone mineral content (BMC) to make up shortcomings of aBMD in osteoporosis diagnosis.@*METHODS@#In this multi-center epidemiological study, BMC and aBMD of lumbar spines (n = 5510) and proximal femurs (n = 4710) were measured with dual energy X-ray absorptiometry (DXA). We analyzed the correlation between the bone mass and body weight in all subjects including four age groups (50 years). And then the body weight was used for standardizing BMC (named wBMC) and applied for the epidemiological analysis of osteoporosis.@*RESULTS@#The correlation of body weight and BMC is 0.839 to 0.931 of lumbar vertebra 1-4 (L1-4), and 0.71 to 0.95 of femoral neck in different age groups. When aBMD was applied for diagnosing osteoporosis, the prevalence was 7.55%, 16.39%, and 25.83% in patients with a high, intermediate, and low body weight respectively. However, the prevalence was 21.8%, 18.03%, and 11.64% by wBMC applied for diagnosing osteoporosis. Moreover, the prevalence of osteoporosis increased by 3.76% by wBMC with the body weight increased by 5 kg. The prevalence decreased by 1.94% when the body weight decreased by 5 kg.@*CONCLUSIONS@#wBMC can reduce the missed diagnosis in patients with large body weight and reduce misdiagnosis in those with small body weight. Including children, wBMC may be feasible for osteoporosis diagnosis individuals at any age.

Mechanism of carvedilol against myocardial ischemia/reperfusion injury / 医学研究生学报

Objective Carvedilol (Cvd) has a potential cardioprotective effect against myocardial ischemia/reperfusion (I/R) injury but its molecular mechanism is not yet clarified. The present study aimed to investigate whether the mechanism of Cvd against myocardial I/R injury-induced cardiomyocyte apoptosis is associated with its protection of the myocardium by modulating the unfolded protein response (UPR).Methods Forty male SD rats were randomly divided into five groups of equal number, sham operation, I/R, I/R + UPR agonist dithiothreitol (I/R+DTT), I/R + DTT with Cvd pretreatment at 5 mg/kg (I/R+DTT+Cvd), and I/R with Cvd pretreatment at 5 mg/kg (I/R+Cvd). The myocardial infarct size (infarct area / area-at-risk, IA/AAR) was measured by TCC & Evans blue double staining, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) detected by echocardiography, the apoptosis of the myocardiocytes determined by TUNEL staining, the activation of the UPR signaling pathway and the expressions of Caspase-12 and Casoase-3 detected by Western blot, and the concentrations of LDH and CK-MB assayed with the detection kit, followed by a comprehensive evaluation of the effects of Cvd on myocardial I/R injury.Results Myocardial IA/AAR was significantly increased in the I/R+DTT group as compared with the sham operation control (\[54.1±3.28\] % vs \[24.25±3.19\] %, P<0.05), higher in the I/R+DTT and I/R+DTT+Cvd (P<0.05) but lower in the I/R+Cvd than in the I/R group (P<0.05), and lower in the I/R+DTT+Cvd than in the I/R+DTT group (P<0.05). In comparison with the sham operation control, all the other four groups showed significantly decreased LVEF and LVFS (P<0.05), both remarkably lower in the I/R+DTT (\[44.5±1.56\] % and \[19.2±2.23\] %) than in the I/R group (\[61.5±2.63\] % and \[28.4±1.42\] %) (P<0.05), but higher in the I/R+DTT+Cvd and I/R+Cvd groups (P<0.05). The apoptosis rate of the cardiomyocytes was markedly increased in the I/R, I/R+DTT, I/R+DTT+Cvd, and I/R+Cvd groups as compared with that in the sham operation control (\[24.4±2.65\]%, \[48.3±1.62\]%, \[32.6±1.28\] % and \[13.2±2.21\]% vs \[6.2±1.27\]%, P<0.05), higher in the I/R+DTT and I/R+DTT+Cvd (P<0.05) but lower in the I/R+Cvd than in the I/R group (P<0.05). Compared with the sham operation control, the other four groups exhibited significantly elevated levels of expressions of the GRP78, CHOP and ATF6 proteins (P<0.05), all markedly higher in the I/R+DTT (P<0.05) but lower in the I/R+Cvd (P<0.05) and that of GRP78 lower in the I/R+DTT+Cvd than in in the I/R group (P<0.05), and all lower in the I/R+DTT+Cvd than in the I/R+DTT group (P<0.05).Conclusion Carvedilol can significantly alleviate the apoptosis of cardiomyocytes, and its molecular mechanism is related to its inhibitory effect on the UPR pathway.

Distribution of Traditional Chinese Medical Syndromes and Clinical Characteristics of Influenza in South of Five Ridges / 广州中医药大学学报

Objective To investigate the distribution of traditional Chinese medical syndromes and clinical characteristics of influenza in South of Five Ridges.Methods A retrospective analysis was carried out in 162 cases of influenza patients admitted from outpatient department,emergency department and inpatient department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2014 to 2016.The distribution of clinical manifestations and syndrome types of the included influenza patients was analyzed.Results The average age of the included influenza patients was 35.76 ± 11.4 years old.The clinical syndromes were mainly characterized by fever,aversion to cold and chills,fatigue and weakness.And damp-accumulation manifestations of heaviness in the body,poor appetite,dry mouth without willing to drink,nausea and vomiting were also predominant.The main syndrome types were wind-heat attacking defense phase syndrome,wind-cold fettering exterior syndrome,heat-toxin attacking lung syndrome,heat-toxin accumulating lung syndrome,and damp syndrome.Of the syndrome types,wind-heat attacking defense phase syndrome and heat-toxin attacking lung syndrome were the leading types,accounting for 77.79％ and interweaving with damp syndrome and heat-damp syndrome.Conclusion The syndromes of influenza patients in South of Five Ridges are usually complicated by damp syndrome or damp-heat syndrome,and the predominant syndrome type is wind-heat interweaved with damp syndrome,which is correlated with the climate being damp and hot in South of Five Ridges.

Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of red yeast rice (RYR) on blood lipid levels, aortic atherosclerosis (AS), and plaque stability in apolipoprotein E gene knockout (ApoE-/-) mice.</p><p><b>METHODS</b>Twenty-four ApoE-/- mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups (n = 8 in each group): model group (ApoE-/- group), RYR group (ApoE-/- + RYR group), and simvastatin group (ApoE-/- + simvastatin group). Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured with enzyme-linked immunosorbent assay. The level of high sensitivity C-reaction protein (Hs-CRP) was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9 (MMP-9) and nuclear factor κB (NF-κB) in aorta were tested by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein (a), and apolipoprotein B100 in ApoE-/- mice (P<0.01). Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α (P<0.01). RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta.</p><p><b>CONCLUSIONS</b>RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflflammatory signaling pathways.</p>

Inter-isoform Hetero-dimerization of Human UDP-Glucuronosyltransferases (UGTs) 1A1, 1A9, and 2B7 and Impacts on Glucuronidation Activity.

Human UDP-glucuronosyltransferases (UGTs) play a pivotal role in phase II metabolism by catalyzing the glucuronidation of endobiotics and xenobiotics. The catalytic activities of UGTs are highly impacted by both genetic polymorphisms and oligomerization. The present study aimed to assess the inter-isoform hetero-dimerization of UGT1A1, 1A9, and 2B7, including the wild type (1A1*1, 1A9*1, and 2B7*1) and the naturally occurring (1A1*1b, 1A9*2/*3/*5, and 2B7*71S/*2/*5) variants. The related enzymes were double expressed in Bac-to-Bac systems. The fluorescence resonance energy transfer (FRET) technique and co-immunoprecipitation (Co-IP) revealed stable hetero-dimerization of UGT1A1, 1A9, and 2B7 allozymes. Variable FRET efficiencies and donor-acceptor distances suggested that genetic polymorphisms resulted in altered affinities to the target protein. In addition, the metabolic activities of UGTs were differentially altered upon hetero-dimerization via double expression systems. Moreover, protein interactions also changed the regioselectivity of UGT1A9 for querectin glucuronidation. These findings provide in-depth understanding of human UGT dimerization as well as clues for complicated UGT dependent metabolism in humans.

Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities.

Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation.

Molecular docking screening using agonist-bound GPCR structures: probing the A2A adenosine receptor.

Crystal structures of G protein-coupled receptors (GPCRs) have recently revealed the molecular basis of ligand binding and activation, which has provided exciting opportunities for structure-based drug design. The A2A adenosine receptor (A2AAR) is a promising therapeutic target for cardiovascular diseases, but progress in this area is limited by the lack of novel agonist scaffolds. We carried out docking screens of 6.7 million commercially available molecules against active-like conformations of the A2AAR to investigate whether these structures could guide the discovery of agonists. Nine out of the 20 predicted agonists were confirmed to be A2AAR ligands, but none of these activated the ARs. The difficulties in discovering AR agonists using structure-based methods originated from limited atomic-level understanding of the activation mechanism and a chemical bias toward antagonists in the screened library. In particular, the composition of the screened library was found to strongly reduce the likelihood of identifying AR agonists, which reflected the high ligand complexity required for receptor activation. Extension of this analysis to other pharmaceutically relevant GPCRs suggested that library screening may not be suitable for targets requiring a complex receptor-ligand interaction network. Our results provide specific directions for the future development of novel A2AAR agonists and general strategies for structure-based drug discovery.

Effect of low molecular weight heparin combined with low dose aspirin on hormone level and immune function in patients with recurrent spontaneous abortion / 中国生化药物杂志

Objective To study effect of low molecular weight heparin combined with aspirin on hormone level and immune function in treatment of recurrent spontaneous abortion.Methods 118 cases patients with recurrent spontaneous abortion from January 2013 to December 2013 were divided into observation group and control group, control group was given low-dose aspirin therapy, observation group was given low molecular weight heparin combined with low-dose aspirin.hormone levels, immune function, therapy effect were compared between two groups.Result Clinical curative effect:observation group prevent miscarriage success rate 86.44% was significantly higher than control group 55.93%(χ2 =13.387, P0.05).Conclusion Low molecular weight heparin combined with aspirin therapy help to improve recurrent hormone levels and immune function, then improve prevent miscarriage success rate.

Clinical study on treatment of carotid atherosclerosis with extraction of polygoni cuspidati rhizoma et radix and crataegi fructus: a randomized controlled trial / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis.</p><p><b>METHOD</b>Sixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1.</p><p><b>RESULT</b>After 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05).</p><p><b>CONCLUSION</b>Detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.</p>

N-(7-Methyl-1,8-naphthyridin-2-yl)acetamide-acetic acid (1/1).

In the title adduct, C11H11N3O·C2H4O2, all non-H atoms of the acetamide mol-ecule are roughly coplanar, with an r.m.s. deviation of 0.0720 Å. The dihedral angle between the ring plane and the acetamide group is 8.5 (2)°. In the crystal, O-H⋯N and N-H⋯O hydrogen bonds link the acetamide and acetic acid mol-ecules.

1,8-Naphthalimide-Cu(ІІ) ensemble based turn-on fluorescent probe for the detection of thiols in organic aqueous media.

A 1,8-naphthalimide-Cu(II) ensemble was rationally designed and synthesized as a new turn-on fluorescent probe utilizing the 'chemosensing ensemble' method for detections of thiols (Cys, Hcy and GSH) with high selectivity over other α-amino acids at pH 7.4 in organic aqueous media (EtOH/HEPES, v/v=9:1). The recognition mechanism was attributed to the remove Cu(II) from the 1,8-naphthalimide-Cu(II) ensemble by thiols and the release of flurescence of ligand 1. Remarkable fluorescence enhancements were therefore observed in the sensing process of thiols by the 1,8-naphthalimide-Cu(II) ensemble. Furthermore, the 1,8-naphthalimide-Cu(II) ensemble was successfully applied to the fluorescence imaging of thiols in CHO cells with high sensitivity and selectivity.

N-(7-Dibromo-methyl-5-methyl-1,8-naphthyridin-2-yl)acetamide-pyrrolidine-2,5-dione (1/1).

In the title co-crystal, C(12)H(11)Br(2)N(3)O·C(4)H(5)NO(2), the naphthyridine derivative and the pyrrolidine-2,5-dione mol-ecules have crystallographic mirror-plane symmetry with all non-H atoms, except the Br atom, located on the mirror plane. In the crystal, N-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into heterodimers. These dimers are further linked into a one-dimensional structure along [010] by weak C-Br⋯O inter-actions [Br⋯O = 3.028 (5) Šand C-Br⋯O = 158.52 (4)°].

Large Stokes shift induced by intramolcular charge transfer in N,O-chelated naphthyridine-BF2 complexes.

Novel N,O-chelated naphthyridine-BF(2) complexes with push-pull structures have been synthesized and characterized. Spectral investigations on these complexes reveal that photoinduced intramolecular charge transfer occurs and results in a large Stokes shift, which is further supported by density functional theory based theoretical calculations.