Copper(I)-Catalyzed Conjugate Addition/Enantioselective Protonation with Selenols and α-Substituted α,ß-Unsaturated Thioamides.

Herein, a copper(I)-catalyzed asymmetric conjugate addition/protonation with selenols and α-substituted α,ß-unsaturated thioamides is disclosed, which affords a series of chiral selenides in high to excellent enantioselectivity. As for both selenols and α-substituted α,ß-unsaturated thioamides, the reaction enjoys broad substrate scopes. The present catalytic system is also successfully applied to asymmetric selenation of ß-substituted α,ß-unsaturated thioamides. A [Cu-(R,RP )-TANIAPHOS]-SePh species is characterized by its 77 Se NMR spectra, which gives a chemical shift at δ 462 ppm. Moreover, a {[Cu-(R)-TOL-BINAP]-SePh}2 species is characterized by X-ray analysis, which confirms the formation of Cu-Se bond in the reaction. Finally, the transformations of the thioamide group to amine and thioester are demonstrated to be straightforward.

S-Nitrosylation of Akt by organic nitrate delays revascularization and the recovery of cardiac function in mice following myocardial infarction.

The effects of long-term nitrate therapy are compromised due to protein S-Nitrosylation, which is mediated by nitric oxide (NO). This study is to determine the role of Akt S-Nitrosylation in the recovery of heart functions after ischaemia. In recombinant Akt protein and in HEK293 cells, NO donor decreased Akt activity and induced Akt S-Nitrosylation, but was abolished if Akt protein was mutated by replacing cysteine 296/344 with alanine (Akt-C296/344A). In endothelial cells, NO induced Akt S-Nitrosylation, reduced Akt activity and damaged multiple cellular functions including proliferation, migration and tube formation. These alterations were ablated if cells expressed Akt-C296/344A mutant. In Apoe-/- mice, nitroglycerine infusion increased both Akt S-Nitrosylation and infarct size, reduced Akt activity and capillary density, and delayed the recovery of cardiac function in ischaemic hearts, compared with mice infused with vehicle. Importantly, these in vivo effects of nitroglycerine in Apoe-/- mice were remarkably prevented by adenovirus-mediated enforced expression of Akt-C296/344A mutant. In conclusion, long-term usage of organic nitrate may inactivate Akt to delay ischaemia-induced revascularization and the recovery of cardiac function through NO-mediated S-Nitrosylation.

[Tongue Coat Information Extraction of the Traditional Chinese Medicine with Hyperspectral Image].

Tongue coat information extraction plays an important role in disease diagnosis for the traditional Chinese medicine. For the purpose of quantifying the tongue coat properties in traditional Chinese medicine, most of the existing methods are based on computerized image analysis, carrying out RGB color space in a tongue imaging captured with digital camera. However, those methods cannot meet the requirements of clinical medicine. To explore more information about the tongue objectively, a new approach to analyze tongue information based on hyperspectral images is presented. Hyperspectral images are acquired using the hyperspectral imaging system in the spectral range of 370.200 0 to 992.956 0 nm (343bands), and the traditional Chinese medicine clinical diagnosis information is recorded. The main region of interest (ROI) in the samples is extracted while the background is removed from the tongue image, then tongue information of ROI is analyzed. The largest different spectral characteristics between tongue proper and tongue coat are found in the wavelength range of about 525 to 600 nm. Nine wavelengths tongue spectral images from 382.108 0 to 963.668 0 nm are extracted, then comparing with the actual tongue situation, we find that the spectral image at 527.548 0 nm band can better reflect the actual tongue situation than others. The experiment results show that hyperspectral imaging technique is very helpful for tongue coat information extraction of the traditional Chinese medicine, and this new analysis approach can provide a fast and simple non-invasive detection method for tongue coat segmentation and tongue coat information extraction.

Covalent organic framework reinforced hollow fiber bar for extraction and detection of bisphenols from beverages.

Bisphenols (BPs) can migrate from packaging materials into foods, resulting in potentially harmful residues. For example, accumulation of BPs is associated with endocrine disorders. Owing to matrix effects, development of an effective and eco-friendly sample pretreatment would be helpful for BPs detection in beverages packed in plastic containers. In this work, an extraction bar, composed of hollow fiber (HF) functionalized with covalent organic frameworks (COF@Tp-NDA) and 1-ocanol, was prepared for extraction of five BPs simultaneously. The synergistic effect of COF@Tp-NDA and 1-octanol improved the extraction efficiency of BPs from milk-based beverage, juice, and tea beverage. Under optimal conditions, limits of detection ranged from 0.10 to 2.00 ng mL-1 (R2 ≥ 0.9974) and recoveries ranged from 70.1 % to 106.8 %. This method has the potential to enrich BPs, supporting their accurate determination in complex beverages.

Resistin-like molecule alpha enhances the proliferation and migration of aortic vascular smooth muscle cells.

OBJECTIVE: The mitogenic and chemotactic effects of resistin-like molecule alpha (RELMα) are thought to contribute to vascular remodeling in pulmonary arterial hypertension. Here we evaluate the expression of RELMα in atherosclerotic plaque and investigate its effects on the proliferation and migration of vascular smooth muscle cells (VSMCs). METHODS: An atherosclerotic model was established by feeding 4-week-old C57BL/6J ApoE-/- mice (n = 9) with a high-fat diet. Wild-type 4-week-old C57BL/6J (n = 9) were fed the same diet and were used as controls. RELMα expression was evaluated by immunohistochemistry and quantified using real-time PCR (RT-PCR). A (3)H-thymidine incorporation assay and the Boyden chamber assay, respectively, were used to explore the effects of different concentrations of RELMα on the proliferation and migration of VSMCs. RESULTS: Immunohistochemistry identified positively stained granules in atherosclerotic plaques. These results were confirmed by detection of RELMα mRNA using RT-PCR. We also demonstrated that in vitro exposure to RELMα significantly promoted the proliferation and migration of VSMCs in a dose-related manner (p < 0.01). CONCLUSIONS: RELMα expressed in atherosclerotic plaque of ApoE-/- mice appears to enhance the proliferation and migration of aortic VSMCs in a dose-related manner.

[Assessment of the reproducibility of occlusal morphology for digital full crown designed by mandibular trajectory data].

PURPOSE: To metrically assess the reproducibility of mandibular trajectory data and mean frame parameter in guiding the design of occlusal morphology of prosthesis. METHODS: Fifteen subjects with complete dentition were selected, including 6 females and 9 males, with an average age of 22-30 years old. The mandibular trajectory data and mean frame parameter were used to guide the design of occlusal morphology of the prosthesis in the CAD system, then the occlusal morphology was compared to the original natural teeth. The data were statistically analyzed by SPSS 25.0 software package. RESULTS: The general deviation of occlusal morphology between the prosthesis guided by mandibular trajectory data and mean frame parameter with the natural teeth was as follows: mean positive distance was (269.9±63.1) µm, (318.7±51.3) µm; mean negative distance was (-175.8±78.2) µm, (-253.7±65.6) µm; root mean square (RMS) was (267.1±84.9) µm and (304.1±82.2) µm. The vertical distance on mesial buccal cusp was (197.6±86.2) µm and (288.0±79.6) µm，distal buccal cusp was (176.3±85.3) µm and (297.7±63.2) µm, mesial lingual cusp was (171.6±62.4) µm and (246.4±62.8) µm, distal lingual cusp was (166.2±64.6) µm and (232.5±70.7) µm, central fossa was (104.9±42.2) µm and (219.1±69.1) µm. RMS, mean(-) and vertical differences of central fossa and distal buccal cusp were significantly different(P＜0.05). CONCLUSIONS: The occlusal morphology of the prosthesis designed under the guidance of mandibular trajectory data and mean frame parameter both have significant differences with natural occlusion, but the deviation guided by mandibular trajectory data is lower.

Matrix mechanics regulate the polarization state of bone marrow-derived neutrophils through the JAK1/STAT3 signaling pathway.

Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects. STATEMENT OF SIGNIFICANCE.

Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions.

Two-component systems (TCS) are universal among bacteria and play critical roles in gene regulation. Our understanding of the contributions of TCS in the biology of the Borrelia is just now beginning to develop. Borrelia burgdorferi, a causative agent of Lyme disease, harbours a TCS comprised of open reading frames (ORFs) BB0419 and BB0420. BB0419 encodes a response regulator designated Rrp1, and BB0420 encodes a hybrid histidine kinase-response regulator designated Hpk1. Rrp1, which contains a conserved GGDEF domain, undergoes phosphorylation and produces the secondary messenger, cyclic diguanylate (c-di-GMP), a critical signaling molecule in numerous organisms. However, the regulatory role of the Rrp1-Hpk1 TCS and c-di-GMP signaling in Borrelia biology are unexplored. In this study, the distribution, conservation, expression and potential global regulatory capability of Rrp1 were assessed. rrp1 was found to be universal and highly conserved among isolates, co-transcribed with hpk1, constitutively expressed during in vitro cultivation, and significantly upregulated upon tick feeding. Allelic exchange replacement and microarray analyses revealed that the Rrp1 regulon consists of a large number of genes encoded by the core Borrelia genome (linear chromosome, linear plasmid 54 and circular plasmid 26) that encode for proteins involved in central metabolic processes and virulence mechanisms including immune evasion.

Alantolactone induces gastric cancer BGC-823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway.

Alantolactone (ALT), a natural sesquiterpene lactone, has been suggested to exert anti-cancer activities in various cancer cell lines. However, the effects and mechanisms of action of ALT in human gastric cancer remains to be elucidated. In the present study, the effects of ALT on BGC-823 cells were examined and the underlying molecular mechanisms associated with these effects were investigated. Cell viability was detected by using an MTT assay. Cell cycle, cell apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression levels of proteins of interest were analyzed by western blot assay. The results demonstrated that ALT triggered apoptosis and induced G0/G1 phase arrest in a dose-dependent manner. Furthermore, the expression level of the anti-apoptosis protein Bcl-2 was downregulated, and expression of the pro-apoptosis proteins Bax and cleaved PARP were significantly upregulated. The cell cycle-associated proteins cyclin-dependent kinase inhibitor 1 and cyclin-dependent kinase inhibitor 1B were also increased, while cyclin D1 was deceased. In addition, ALT induced apoptosis via the inhibition of RAC-alpha serine/threonine-protein kinase (AKT) signaling and ROS generation, which was effectively inhibited by the ROS scavenger, N-acetyl cysteine. Therefore, the results from the present study indicated that the ROS-mediated inhibition of the AKT signaling pathway serves an important role in ALT-induced apoptosis in BGC-823 cells. In conclusion, the results demonstrated that ALT exerted significant anti-cancer effects against gastric cancer cells in vitro.

Intracellular acidosis via activation of Akt-Girdin signaling promotes post ischemic angiogenesis during hyperglycemia.

AIMS: The impaired angiogenesis is the major cause of diabetic delayed wound healing. The molecular insight remains unknown. Previous study has shown that high glucose (HG) activates Na+/H+ exchanger 1 (NHE1) and induces intracellular alkalinization, resulting in endothelial dysfunction. The aim of this study is to investigate whether activation of NHE1 in endothelial cells by HG damages the angiogenesis in vitro and in vivo. METHODS AND RESULTS: We used western blot to detect the phosphorylations of both Akt and Girdin, and pH-sensitive BCECF fluorescence to assay NHE1 activity and pHi value, respectively. The angiogenesis was evaluated by measuring the number of tube formation in vitro, and blood perfusion by laser doppler and neovascularization by staining CD31 in vivo. Our results indicated that induction of intracellular acidosis (IA) increased p-Akt and p-Girdin in human umbilical vein endothelial cells (HUVEC). HG activated NHE1 and increased pHi value in a time-dependent manner, associated with the decreased phosphorylations of both Akt and Gridin, while inhibition of NHE1 by amiloride abolished the HG-induced reductions of p-Akt and p-Girdin. However, silence of Akt by siRNA transfection or pharmacological inhibitors (wortmannin and LY294002) bypassed IA-induced Girdin phosphorylation. Overexpression of constitutively active Akt abolished HG-reduced Girdin phosphorylation. In addition, upregulation of Akt or inhibition of NHE1 remarkably attenuated HG-impaired tube formation in HUVEC. In vivo study revealed that amiloride dramatically rescued hyperglycemia-delayed blood perfusion and neovascularization by augmenting ischemia-induced angiogenesis. CONCLUSION: IA promotes ischemia-induced angiogenesis via Akt-dependent Girdin phosphorylation in diabetic mice.

Anticancer activity and underlying mechanism of neogambogic acid.

Garcinia, a kind of dry resin secreted by Garcinia hanburyi Hook. F. G., is a traditional Chinese medicine with various biological functions such as detoxification, anti-inflammatory, and anthelmintic activities. Recent studies suggest that garcinia has potential anticancer activity. Increasing evidences indicate that the main active monomer gambogic acid isolated from garcinia can inhibit the growth of various cancer cells. Neogambogic acid is an isolated compound with a similar chemical structure as gambogic acid. Preliminary studies show that the neogambogic acid can selectively inhibit the growth of various cancer cells, and has a broader antitumor activity and lower toxicity than gambogic acid. In this review, we summarize the advances made in the investigation of the anti-tumor effect of neogambogic acid in recent years.

[Dioxin Pollution and Occupational Inhalation Exposure of PCDD/Fs in Municipal Solid Waste Incinerator].

To assess the pollution levels, characteristics, and the pollution sources and occupational inhalation exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs)in the workshops,ambient air samples in different types of incinerators of two municipal solid waste incinerators(MSWI) were collected and analyzed. The results showed that ① The I-TEQ concentration ranged from 0.034-2.152 pg·m-3in the two waste incineration plants, and the most sites' I-TEQ exceeded the ambient air quality standard. Besides, the I-TEQ concentration behind the incineration plant was higher than others. ② The dioxins in incineration plant were dominated by OCDD and 1,2,3,4,6,7,8-HpCDD. For MSWI A, the flue gas and the fly ash had major effect on PCDD/Fs, while the dioxins pollution in MSWI B was only affected by the fly ash. ③ Occupational inhalation exposure of PCDD/Fs was 0.01-1.10 pg·(kg·d)-1 in incineration plant, some occupational inhalation exposure values exceeded the evaluation standard, and the areas behind the incinerators were evaluated to have a high exposure risk.

[Heavy metal pollution characteristics and ecological risk analysis for soil around Haining electroplating industrial park].

The pollution status and potential ecological risks of heavy metal in soils around Haining electroplating industrial park were studied. Hakanson index approach was used to assess the ecological hazards of heavy metals in soils. Results showed that average concentrations of six heavy metals (Cu, Ni, Pb, Zn, Cd and Cr) in the soils were lower than the secondary criteria of environmental quality standard for soils, indicating limited harmful effects on the plants and the environment in general. Though the average soil concentrations were low, heavy metal concentrations in six sampling points located at the side of road still exceeded the criteria, with excessive rate of 13%. Statistic analysis showed that concentrations of Cu and Cd in roadside soils were significantly higher than those in non-roadside soils, indicating that the excessive heavy metal accumulations in the soil closely related with traffic transport. The average potential ecological hazard index of soils around Haining electroplating industrial park was 46.6, suggesting a slightly ecological harm. However, the potential ecological hazard index of soils with excessive heavy metals was 220-278, suggesting the medium ecological hazards. Cd was the most seriously ecological hazard factor.

Value of segmental coronary calcium score on diagnosis and interventional treatment of coronary lesions by 320-slice DVCT.

UNLABELLED: The global coronary calcium score has been widely used in the evaluation of coronary plaque burden and cardiovascular disease events. In this study, we investigated the value of segmental coronary calcium score (SCCS) on the diagnosis and interventional treatment. We studied 87 patients with coronary angiography (CAG) and coronary CT angiography (CTA) by 320-slice dynamic volume CT (DVCT). SCCS was determined for each segmental separately. All lesions which SCCS was greater than 0 were enrolled, and were divided into three groups, mild calcification group (SCCS were less than 80), Moderate calcification group (SCCS were more than 80 and less than 200) and Severe calcification group (SCCS were more than 200). From above three groups, lesions received the intervention treatment were elected as subgroup. The position of lesions, plaque morphology, calcification proportion and interventional treatment data were analyzed. Severe calcification group were more frequent in the proximal lesions, stenosis with lesser extent, nubbly and nodular types of plaque, and the inconsistency with CAG was higher than the other two groups (P < 0.05). In the subgroup, more pre-dilatation and post-dilatation balloon were used in severe calcification group, with higher expansion pressure of balloon and stent (P < 0.05), but the diameter of stents was no difference between the three groups. CONCLUSION: SCCS is better than GCCS in the evaluation of coronary calcification, and play an important role in the judgment of stenosis by coronary CT and in the choice of interventional therapeutic devices.

XPC Lys939Gln polymorphism is associated with the decreased response to platinum based chemotherapy in advanced non-small-cell lung cancer.

BACKGROUND: Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer (NSCLC) patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939Gln gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population. METHODS: The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C (XPC) gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method. RESULTS: The distributions of XPC Lys939Gln genotypes differed significantly between the response group (complete + partial responses) and the non-response group (stable + progressive disease; P = 0.022). The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage III (OR, 0.074; 95%CI, 0.008 - 0.704; P = 0.023). The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy. CONCLUSION: Polymorphisms of the XPC gene, Lys939Gln, may be a predictive marker of treatment response for advanced NSCLC patients in stage III.