Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

[Spatial distribution patterns and intraspecific and interspecific associations of dominant shrub species Lonicera fragrantissima var. lancifolia in Huangguan of Qinling Mountains, China]. / ç§¦å²­çš‡å† ä¼˜åŠ¿çŒæœ¨è‹¦ç³–æžœçš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´å ³è”.

In this study, the spatial distribution patterns of individuals with different diameter classes of dominant shrub Lonicera fragrantissima var. lancifolia and the intraspecific and interspecific relationships were analyzed in Qinling Huangguan Plot. The results showed that the diameter class structure of L. fragrantissima var. lancifolia showed a pyramid shape, with a wide bottom and a narrow top. The number of small-diameter class individuals was the largest, showing a good state of renewal and a stable growth, which was conducive to community renewal and succession. Based on Ripley's K function, using univariate and bivariate paired correlation functions, under complete spatial randomness model, heterogeneous Poisson model and antecedent condition model, all individual of the species and their diameter-dividing classes were mainly aggregated, and the aggregation degree decreased with the increases of research scale, and gradually tended to random distribution. Affected by habitat heterogeneity, diffusion restriction and negative density dependence, there was a positive correlation among different intraspecific dia-meter classes, and also a certain degree of no correlation, but without negative correlation. The interspecific relationship was complex. All types of association (no, positive and negative) were observed, but negative association and no association were dominated.

[Spatial distribution pattern and intraspecific association of dominant species Quercus aliena var. acu-tiserrata in Qinling Mountains, China]. / ç§¦å²­ä¼˜åŠ¿ä¹”æœ¨é”é½¿æ§²æ Žçš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† å ³è”.

To explore the spatial distribution and intraspecific correlation of Quercus aliena var. acutiserrata, a domi-nant tree species in a 25 hm2 plot of warm temperate deciduous broadleaved forest in Qinling Mountains, the pair-correlation function g(r) was used to study the spatial pattern and intraspecific association. The results showed that the diameter class structure of Q. aliena var. acutiserrata was bimodal, with a large proportion of young trees (1 cm≤DBH＜5 cm), indicating an increase population structure with good capability of regeneration. The abundance of middle trees (15 cm≤DBH＜25 cm) was slightly more than that of big trees (25 cm≤DBH＜35 cm) and old trees (DBH≥35 cm), but far less than that of young trees and small trees. The spatial distribution of Q. aliena var. acuteserrata was obviously altitude dependent, which mainly distributed in the middle and high altitude areas. Results of complete spatial randomness (CSR) model analysis showed that young trees, small trees, adult trees, big trees, and old trees were aggregated in the large scale (＜60 m). Heterogeneous Poisson (HP) model was used to eliminate habitat heterogeneity. The results of HP model showed that the individual aggregation degree of each diameter class decreased, indicating that the distribution was affected by habitat heterogeneity. At the small scale (＜40 m), spatial correlation was positively correlated between individuals with small diameter gap, whereas the spatial correlation was negative correlation and no correlation between individuals with large diameter gap. At large scale (>40 m), the spatial correlation was positively correlated between large-diameter individuals, but negatively correlated and unrelated between saplings and other diameter individuals. Our results indicated that biological cha-racteristics of Q. aliena var. acutiserrata and habitat heterogeneity were important drivers for the formation of population spatial pattern.

Amniotic membrane for covering high myopic macular hole associated with retinal detachment following failed primary surgery.

AIM: To evaluate the therapeutic effect of amniotic membrane (AM) for covering high myopic macular hole associated with retinal detachment following failed primary surgery. METHODS: Seventeen eyes of 17 patients whose axial length was more than 29 mm suffered from macular hole (MH) or MH associated with retinal detachment (RD), and had previously surgery of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and silicone oil (SO) tamponade. Half a year after the surgery, optical coherence tomography (OCT) showed that MH did not heal in all 17 eyes and RD was still maintained in 13 eyes of these 17 eyes. We performed SO removal combined with AM covering on macular area and C3F8 tamponade, and phacoemulsification combined with intraocular lens implantation simultaneously cataract eyes. We followed up these patients for one year. RESULTS: In all 17 eyes, SO was removed successfully, MHs were healed and RDs were reattached. One eye (5.89%, 1/17) had AM shifted half a month after surgery and underwent a second surgery to adjust the position of the AM and supplement C3F8. After surgery, the visual acuity (VA) improved in 15 eyes (88.24%, 15/17), no change in two eyes (11.76%, 2/17). No serious complications occurred in all eyes. CONCLUSION: AM covering is helpful to rescue the previous failure surgery of high myopic MH.

Erythroxylumaustroguangdongense (Erythroxylaceae), a new species from Guangdong, China.

Erythroxylumaustroguangdongense (Erythroxylaceae), a new species from Guangdong Province, China, is described and illustrated. This new species is morphologically most similar to E.calyptratum, but is distinguished by the leathery leaf blade with fewer pairs of secondary veins and flowers borne on leafless nodes of the basal part of the current branch with much longer pedicels and sub-rectangular petal appendages. This is the second native species of Erythroxylum recorded from China.

[Species composition and community structure of warm temperate deciduous broadleaved forests in Huangguan of Qinling Mountains, China]. / ç§¦å²­çš‡å† æš–æ¸©æ€§è½å¶é˜”å¶æž—ç‰©ç§ç»„æˆä¸Žç¾¤è½ç»“æž„.

The Qinling Mountain is a natural boundary between warm temperate zone and subtropical zone. While the China Forest Biodiversity Monitoring Network (CForBio) have basically covered most of the climate regions in China, few plots were located in the climate transition zone. Following the field protocol of CForBio and the Center for Tropical Forest Science (CTFS), a 25 hm2(500 m×500 m) forest plot was established in Huangguan Nature Reserve in Shaanxi Province, China, in 2019. In this study, we analyzed species composition, flora characteristics, diameter class structure, and spatial distribution patterns of dominant tree species based on the data of all woody species with a diameter at breast height (DBH) ≥1 cm. The results showed that there were 75137 woody individuals with DBH ≥1 cm in the plot (95679 when including branching individuals), belonging to 121 species, 83 genera and 44 families. The flora type at the genera level was mainly temperate, accounting for 71.1% of the total genera, and mixed with some tropical components. The dominant species in the community were obvious, with the number of individuals in the top 5 species exceeding 40% of the total number of individuals, the number of individuals in the top 50 species accounting for 95% of the total number of individuals, and the number of individuals in the remaining 61 species being less than 5% of the total. The diameter distribution of all woody indivi-duals in the plot was inverted 'J' type. Spatial distribution patterns varied across the four most abundant species with importance value >5. The degree of aggregation within species decreased with the increases of scales, while the spatial distribution of different species was affected by environmental heterogeneity. Warm-temperate deciduous broadleaved forest in Qinling Mountains had abundant species, stable community structure and good regeneration, reflecting the typical characteristics of the transition from warm temperate zone to subtropical zone. Environmental heterogeneity might be an important factor affecting the spatial distribution of tree species in the plot.

Dendrobium officinale Flower Extraction Mitigates Alcohol-Induced Liver Injury in Mice: Role of Antisteatosis, Antioxidative, and Anti-Inflammatory.

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol-induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol-induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll-like receptor-4 (TLR-4) and nuclear factor kappa-B P65 (NF-κB P65). Thus, DOFE exhibited a significant protective effect against alcohol-induced liver injury through its antisteatosis, antioxidative, and anti-inflammatory effect.

[Role of pyroptosis in bilirubin-induced microglial injury].

OBJECTIVE: To study whether pyroptosis is involved in the bilirubin-induced injury of primary cultured rat cortical microglial cells. METHODS: Primary cultured rat cortical microglial cells were randomly administered with 30 µmol/L bilirubin (bilirubin group), 30 µmol/L bilirubin following 30 µmol/L VX-765 pretreatment (VX-765+bilirubin group), or an equal volume of dimethyl sulfoxide (control group). Modified MTT assay was used to measure the viability of microglial cells. Western blot was used to measure the expression of the pyroptosis-related proteins Caspase-1 and gasdermin D (GSDMD). Lactate dehydrogenase (LDH)-release assay was used to evaluate the cytotoxicity of microglial cells. EtBr/EthD2 with different molecular weights (394 Da/1 293 Da) was used to measure the size of plasma membrane pores. ELISA was used to measure the level of the inflammatory factor interleukin-1ß (IL-1ß) in culture supernatant. RESULTS: After bilirubin stimulation, the viability of microglial cells decreased and LDH release increased, both in a time-dependent manner. Compared with the control group, the bilirubin group had a significantly higher positive rate of small-molecule EtBr passing through the cell membrane (P<0.001), while there was no significant difference in the pass rate of large-molecule EthD2 between groups (P>0.05). The expression of activated Caspase-1 significantly increased at 0.5 hour after bilirubin stimulation (P<0.05), and that of activated GSDMD significantly increased at 6 hours after bilirubin stimulation (P<0.05). The release of IL-1ß significantly increased at 6 hours after bilirubin stimulation and reached the peak at 24 hours (P<0.001). Compared with the bilirubin group, the VX-765+bilirubin group had a significant increase in cell viability (P<0.05) and significant reductions in the expression of activated GSDMD, the pass rate of EtBr, and the release of LDH and IL-1ß (P<0.05). CONCLUSIONS: Pyroptosis is involved in bilirubin-induced injury of primary cultured microglial cells.

An effective classifier based on convolutional neural network and regularized extreme learning machine.

An effective classifier combining convolutional neural network and regularized extreme learning machine (called as CNN-RELM) is presented in this paper. Firstly, CNN-RELM trains the convolutional neural network (CNN) using the gradient descent method until the learning target accuracy reaches. Then the fully connected layer of CNN is replaced by regularized extreme learning machine (RELM) optimized by genetic algorithm and the rest layers of the CNN remain unchanged. The experiments on different face databases are given to evaluate the performance of CNN-RELM. The experimental results show that CNN-RELM is a feasible classifier and it outperforms CNN and RELM. Due to the uniting of CNN and RELM, CNN-RELM have the advantages of CNN and RELM and it is easier to learn and faster in testing.

A revised classification of Chinese Davalliaceae based on new evidence from molecular phylogenetics and morphological characteristics.

Although the phylogenetic framework of Davalliaceae is known, the classification of Chinese Davalliaceae is still controversial. In this study, a molecular phylogenetic tree of 60 accessions, including 29 species produced in China, was constructed using five plastid DNA markers-atpB, atpB-rbcL, rbcL, rbcL-accD, and accD. New data on studied specimens, field investigations, and scanning electron microscopy analysis of leaf epidermis and spores were used to reclassify Chinese Davalliaceae. The taxonomic position of Davallia canariensis was confirmed based on new evidence and a new key to sections of Chinese Davalliaceae was proposed. The taxonomically controversial genus Paradavallodes was confirmed as a polyphyletic group, and it was assigned to Davallia sect. Trogostolon and Davallia sect. Davallodes. Further, species endemic to China were delimited, 21 species were admitted to six sections of Davallia, two new combinations were proposed, two new synonyms were defined and a new key to Chinese species of Davalliaceae was presented.

[Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons].

OBJECTIVE: To investigate the role of caspase-1 activation in bilirubin-induced neuronal injury and the protective effect of VX-765 against bilirubin-induced neurotoxicity in cultured primary rat hippocampal neurons. METHODS: Cultured primary rat hippocampal neurons were exposed to DMSO (control group), 50 µmol/L bilirubin, or 50 µmol/L bilirubin 1 h after 50 µmol/L VX-765 treatment. The expressions of NLRP3 and caspase-1 in the neurons were detected by Western blotting, and the relative cell survival and death rates were assessed with a modified MTT assay, lactate dehydrogenase assay and Typan blue staining. Interleukin-18 (IL-18) concentration in the culture supernatant was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: In cultured primary rat hippocampal neurons, bilirubin exposure for 3 and 6 h caused significant increases in the expressions of NLRP3 and activated caspase-1 compared with those in the control group (P<0.05). Pretreatment of the cells with VX-765 obviously suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative survival rate of the neurons was (84.02∓2.31)% in VX-765 intervention group, significantly higher than that in bilirubin group (P<0.05) but lower than that in the control group (P<0.05); LDH release rate in VX-765 intervention group was (10.78∓1.58)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). The cell death rate in VX-765 intervention group was (5.58∓1.23)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). CONCLUSION: In cultured primary rat hippocampal neurons, caspase-1 activation plays a role in bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against bilirubin-induced neuronal injury by inhibiting caspase-1 activation.

Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults.

The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 µmol/L) and prevalence rate of hyperuricemia (HUA) (25.7% v.s. 47.3%, p < 0.001). After adjustment for insulin resistance (IR), components of metabolic syndrome (MetS) and other potential confounders, elevated SUA is independently associated with increased risk of NAFLD, with the adjusted OR of 1.528-2.031 (p < 0.001). By using multivariable fractional polynomial (MFP) modeling, the best FP transformation model shows that SUA was independently and linearly associated with risk of NAFLD. The one-pathway model by using structural equation modeling (SEM) about the relationships among SUA, IR, components of metabolic syndrome and NAFLD fits well (χ2 = 57.367, p < 0.001; CFI = 0.998; TLI = 0.992; and RMSEA = 0.048) and shows SUA might increase the risk of NAFLD directly besides of the indirect effects through increasing fasting insulin, blood pressure, triglyceride and decreasing HDL-C levels. Our results imply that elevated SUA may play an important role in NAFLD pathogenesis.

[Establishing a minimum data set of soil quality assessment for cold-waterlogged paddy field in Fujian Province, China].

The yields of cold-waterlogged (CW) paddy fields widely spreading in Jiangnan mountainous areas are moderate or low but have a high potential to be increased. Based on data including 41 soil characteristics of 17 pairs of typical surface soils of cold-waterlogged paddy field and non cold-waterlogged (NCW) paddy field at a neighboring landscape unit in Fujian Province, various index differences of soil properties and causes between CW paddy field and NCW paddy field were systematically studied, and a minimum data set (MDS) of soil quality assessment for CW paddy field was established by principal component analysis. By pair analysis, soil characteristics of CW paddy field showed that the content of organic matter increased by 31.7%, but the microbial biomass C decreased by 37.8%, which belonged to active soil organic matter component. The content of ferrous iron (Fe2+) increased by 177.0%, but the available phosphorus (P) and potassium (K) decreased by 52.3% and 22.8%, respectively. Catalase and invertase activities increased by 58.3% and 22. 1%, but phosphatase, nitrate reductase activities and microflora decreased by 47. 8%, 66.6% and 29.8%-46.0%, respectively. The sand content increased about 8.0%, but the water immersed bulk density decreased by 25.8%. There were significant differences of indices for 28 of all 41 soil characteristics. Five principal components cumulatively exhibiting about 78.5% contribution were concluded from the 28 soil characteristics to reflect characteristics related to soil biochemistry, active organic nitrogen, reducing barriers, physical and chemical nutrients, respectively. Eventually, correlation analysis combined with expert experience method were applied to optimize MDS containing six factors for soil quality assessments, including C/N, bacteria, microbial biomass N, total reducing agents, physical sand and total P.

[Influence of paddy rice-upland crop rotation of cold-waterlogged paddy field on crops produc- tion and soil characteristics].

Two consecutive years (4-crop) experiments were conducted to study the influence of different paddy rice-upland crop rotation in cold-waterlogged paddy field on the growth of crops and soil characteristics. The result showed that compared with the rice-winter fallow (CK) pattern, the two-year average yield of paddy rice under four rotation modes, including rape-rice (R-R), spring corn-rice (C-R), Chinese milk vetch-rice (M-R) and bean-rice (B-R), were increased by 5.3%-26.7%, with significant difference observed in C-R and R-R patterns. Except for M-R pattern, the annual average total economic benefits were improved by 79.0%-392.4% in all rotation pattern compared with the CK, and the ration of output/input was enhanced by 0.06-0.72 unit, with the most significant effect found in the C-R pattern. Likewise, compared with the CK, the contents of chlorophyll and carotenoid, and net photosynthetic rate (Pn) of rice plant were all increased during the full-tillering stage of rice in all rotation patterns. The rusty lines and rusty spots of soils were more obvious compared with the CK during the rice harvest, particularly in R-R, C-R and B-R patterns. The ratio of water-stable soil macro aggregates of plough layer of soil (> 2 mm) decreased at different levels in all rotation patterns while the ratios of middle aggregate (0.25-2 mm, expect for M-R) and micro aggregate of soil (< 0.25 mm) were opposite. There was a decreasing trend for soil active reducing agents in all rotation patterns, whereas the available nutrient increased. The amounts of soil bacteria in C-R and B-R patterns, fungi in B-R rotation pattern, cellulose bacteria in R-R, C-R and B-R patterns and N-fixing bacteria in B-R pattern were improved by 285.7%-403.0%, 221.7%, 64.6-92.2% and 162.2%, respectively. Moreover, the differences in all microorganisms were significant. Thus, based on the experimental results of cold-waterlogged paddy field, it was concluded that changing from single cropping rice system to C-R, R-R and B-R rotation patterns had good effect in terms of improving total yield and economic benefits, and soil physical and chemical properties were improved.

[Chemical constituents from capitula of Eriocaulon australe ].

OBJECTIVE: To study the chemical constituents from the capitula of Eriocaulon australe. METHOD: The compounds were isolated and purified by column chromatography and their structures were determined through spectroscopic techniques (NMR)and physicochemical properties. RESULTS: Six compounds were identified from capitula of Eriocaulon australe as (R)-semixanthomegnin( 1) ,tora-lactone-9-0-ß-D-glucopyranoside(2), ( - ) -semivioxanthin-9-0-ß-D-glucopyranoside( 3) ,4-ketopinoresinol(4) ,ß-daucosterol (5) and 3,3'-dihydroxy-4,4'-dimethoxybiphenyl(6). CONCLUSION: Compounds 1 ~ 6 are isolated from this plant and compounds 3 ~ 6 are ob- tained from Eriocaulon genus for the first time. Compound 1 shows DNA scission activity.

Efficient fluorescence resonance energy transfer-based ratiometric fluorescent cellular imaging probe for Zn(2+) using a rhodamine spirolactam as a trigger.

This letter described the design and synthesis of a novel fluorescein-appended rhodamine spirolactam derivative and its preliminary application as a ratiometric fluorescent cellular imaging probe for Zn(2+). The ratiometric fluorescent signal change of the probe is based on an intramolecular fluorescence resonance energy transfer (FRET) mechanism modulated by a specific metal ion induced ring-opening process of the rhodamine spirolactam (acting as a trigger). In the new developed sensing system, the emission peaks of the two fluorophores are well-resolved, which can avoid the emission spectra overlap problem generally met by spectra-shift type probes and benefits for observation of fluorescence signal change at two different emission wavelengths with high resolution. It also benefits for a large range of emission ratios, thereby a high sensitivity for Zn(2+)detection. Under optimized experimental conditions, the probe exhibits a stable response for Zn(2+) over a concentration range from 2.0 x 10(-7) to 2.0 x 10(-5) M, with a detection limit of 4.0 x 10(-8) M. Most importantly, the novel probe has well solved the problem of serious interferences from other transition metal ions generally met by previously reported typical fluorescent probes for Zn(2+) with the di(2-picolyl)amine moiety as the receptor (in this case, the fluorescence response induced by Cd(2+)is even comparable to that of Zn(2+)) and shows a reversible and fast response toward Zn(2+). All these unique features make it particularly favorable for ratiometric cellular imaging investigations. It has been preliminarily used for ratiometric imaging of Zn(2+) in living cells with satisfying resolution.

Inhibition of phosphoinositide 3-kinase ameliorates dextran sodium sulfate-induced colitis in mice.

The critical role of phosphoinositide 3-kinase gamma (PI3Kgamma) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. 5-Quinoxilin-6-methylene-1,3-thiazolidine-2,4-dione (AS605240), a potent PI3Kgamma inhibitor, has been reported to ameliorate chronic inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and atherosclerosis. However, its in vivo effect on intestinal inflammation remains unknown. Here we evaluated the protective and therapeutic potentials of AS605240 in mice with dextran sodium sulfate (DSS)-induced acute and chronic colitis. Our results showed that AS605240 improved survival rate, disease activity index, and histological damage score in mice administered DSS in both preventive and therapeutic studies. AS605240 treatment also significantly inhibited the increase in myeloperoxidase levels, macrophage infiltration, and CD4(+) T-cell number in the colon of DSS-fed mice. The DSS-induced overproduction of colonic proinflammatory cytokines including interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma was significantly suppressed in mice undergoing AS605240 therapy, whereas colonic anti-inflammatory cytokines such as IL-4 were up-regulated. The down-regulation of the phospho-Akt level in immunological cells from the inflamed colon tissue and spleen of AS605240-treated mice was detected both by immunohistochemical analysis and Western blotting. These findings demonstrate that AS605240 may represent a promising novel agent for the treatment of inflammatory bowel disease by suppressing leukocyte infiltration as well as by immunoregulating the imbalance between proinflammatory and anti-inflammatory cytokines.

[Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice].

OBJECTIVE: To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice. METHODS: BALB/c mice were randomly divided into three groups, AS605240 group and vehicle group were injected subcutaneously with emulsions containing CFA and 100 ng peptide which derived from murine cardiac alpha-myosin heavy chain on day 0 and 7 while control group were injected with emulsions containing CFA and PBS. AS605240 group received the oral administration of AS605240 50 mg/(kg x d). The vehicle group received the oral administration of an equal volume of 0.5% carboxymethylcellulose. 21 days after the first immunization, mice were sacrificed, heart and body weight were measured. Myocarditis severity was evaluated according to a semi-quantitative scoring system in heart sections. Immunohistochemistry was performed to determine the effect of AS605240 on myocardium macrophage infiltration; TNF-alpha levels in myocardium were determined by ELISA. In vitro and in vivo chemotaxis assays were performed to determine the effect of AS605240 on MCP-1-induced macrophage chemotaxis. RESULTS: Histological examination of the heart showed that AS605240 significantly relieved the murine myocarditis and reduced heart/body weight ratios in experimental autoimmune myocarditis (EAM) (P< 0.01). Immunohistochemical detection showed that AS605240 significantly suppressed macrophage infiltration into the heart with EAM. ELISA demonstrated that AS605240 down-regulated TNF-alpha levels in myocardium (P<0.01). In vitro and in vivo chemotaxis assays indicated that AS605240 significantly suppressed MCP-1-induced macrophage chemotaxis (P<0.01). CONCLUSION: AS605240 may be an effective drug for autoimmune myocarditis, of which the mechanism is relating to suppress macrophage chemotaxis and macrophage infiltration into myocardium, and to decrease TNF-alpha levels in myocardium.

[Design characteristics of clinical surgery trial based on treatment program of tunnel thread-drawing method for anal fistula: a prospective randomized controlled multicenter trial].

BACKGROUND: Basic principles of clinical trials of nonpharmacologic treatment are similar to those of pharmacologic treatment, but its some special characteristics should be discussed. OBJECTIVE: To explore the design characteristics of clinical surgery trial through the example of tunnel thread-drawing therapy for simple anal fistula. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The clinical trial was designed as a prospective, controlled, randomized multicenter trial. The patients came from Longhua Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western medicine, and Affiliated Hospital of Jianxi University of Traditional Chinese Medicine. Stratified random was performed according to the subtype of anal fistula including low and high anal fistula. Full analysis set was applied to analyze the baseline data, and per protocol set was used in efficacy and safety analysis. The intervention was tunnel thread-drawing method. Classical therapy of thread-drawing method was employed as positive control. MAIN OUTCOME MEASURES: The primary outcomes were course of recovery and cure rate. Quality of life score was used as secondary outcome and anal maximum constriction pressure was considered as safety outcome. RESULTS: Optimal efficiency testing method was used to estimate sample size. A total of 244 subjects were recruited and 236 subjects completed the trial. There was no significant difference in the cure rate of the low and high anal fistula between the treatment group and control group. There was a significant difference in the course of recovery in the patients with low and high anal fistula between treatment group and control group (P<0.01). To the patients with low anal fistula, the course of recovery in the treatment group was (22.26 + or - 8.67) d, and the course of recovery in the control group was (31.41+ or - 11.39) d. To the patients with high anal fistula, the course of recovery in the treatment group was (24.73 + or - 8.15) d, and the course of recovery in the control group was (32.20 + or - 12.60) d. There was no significant difference in the scores of quality of life in the patients with low anal fistula between the treatment group and control group (P>0.05). The trial showed that the tunnel thread-drawing therapy was significantly more effective than classical method for improving the anal sphincter function and patient satisfaction with treatment in the patients with high anal fistula. However the other items of quality of life in the two groups did not show significant difference. There was no any adverse event report in each group. There was no significant difference in the anal maximum constriction pressure in the treatment group before and after the operation. CONCLUSION: The trial shows that the tunnel thread-drawing therapy for simple anal fistula can shorten the course of recovery and improve the patients' quality of life. The training about surgical intervention and clinical implementation program is important in clinical surgery trial. Blind is absolutely difficult to implement and placebo cannot be used in this kind of trial.

Naphthalimide-porphyrin hybrid based ratiometric bioimaging probe for Hg2+: well-resolved emission spectra and unique specificity.

In this paper, we unveil a novel naphthalimide-porphyrin hybrid based fluorescence probe (1) for ratiometric detection of Hg(2+) in aqueous solution and living cells. The ratiometric signal change of the probe is based on a carefully predesigned molecule containing two independent Hg(2+)-sensitive fluorophores with their maximal excitation wavelengths located at the same range, which shows reversibly specific ratiometric fluorescence responses induced by Hg(2+). In the new developed sensing system, the emissions of the two fluorophores are well-resolved with a 125 nm difference between two emission maxima, which can avoid the emission spectra overlap problem generally met by spectra-shift type probes and is especially favorable for ratiometric imaging intracellular Hg(2+). It also benefits from a large range of emission ratios and thereby a high sensitivity for Hg(2+) detection. Under optimized experimental conditions, the probe exhibits a stable response for Hg(2+) over a concentration range from 1.0 x 10(-7) to 5.0 x 10(-5) M, with a detection limit of 2.0 x 10(-8) M. The response of the probe toward Hg(2+) is reversible and fast (response time less than 2 min). Most importantly, the ratiometric fluorescence changes of the probe are remarkably specific for Hg(2+) in the presence of other abundant cellular metal ions (i.e., Na(+), K(+), Mg(2+), and Ca(2+)), essential transition metal ions in cells (such as Zn(2+), Fe(3+), Fe(2+), Cu(2+), Mn(2+), Co(2+), and Ni(2+)), and environmentally relevant heavy metal ions (Ag(+), Pb(2+), Cr(3+), and Cd(2+)), which meets the selective requirements for biomedical and environmental monitoring application. The recovery test of Hg(2+) in real water samples demonstrates the feasibility of the designed sensing system for Hg(2+) assay in practical samples. It has also been used for ratiometric imaging of Hg(2+) in living cells with satisfying resolution, which indicates that our novel designed probe has effectively avoided the general emission spectra overlap problem of other ratiometric probes.