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Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

The scarcity of two-dimensional (2D) magnetic nanostructures has hindered their applications in spintronics, which is attributed to that most magnetic materials exhibit non-van der Waals (nvdWs) structure and it is hard to reduce their thickness to 2D nanostructures. Thus it is eager to develop a promising strategy for free-standing 2D magnetic nvdWs nanostructures. We have achieved free-standing 2D nvdWs hexagonal FeSe with a thickness of 2.9 nm by the reaction between oleylamine-Se complex and Fe2+ with the assistance of Cl-, where the synergetic effects of Cl- and -NH2 lead to the anisotropic growth. Inspiringly, the 2D hexagonal FeSe exhibits intrinsic antiferromagnetic order rooted in Fe2+ and semiconductor nature. In addition, the temperature variation would result in the chemical environment changes of Fe2+, responsible for the temperature-dependent magnetic transitions. This work promotes the potential applications of 2D hexagonal FeSe and the preparation of other 2D nvdWs materials.

OBJECTIVE: To investigate the outcome of endodontic microsurgery and analyze the potential prognostic factors, and to evaluate the value of surgical classification by Kim and Kratchman. METHODS: Collecting clinical examination and radiographical examination of endodontic microsurgery cases (which were followed up at least 1 year), which were classified according to Kim and Kratchman, and we analyzed the outcome of endodontic microsurgery and its potential prognostic factors. RESULTS: 302 patients (400 teeth) who received endodontic microsurgery were included. The one year success rate of endodontic microsurgery was 94.25%. Different classification had significant influences on the outcome of endodontic microsurgery (P0.05). CONCLUSION: Endodontic microsurgery is an effective treatment method for saving affected teeth, and it can get a good result. Tooth position and classification are the potential prognostic factors. The surgical classification of Kim and Kratchman can help to predict the outcome of endodontic microsurgery.

As a typical configuration in plastic deformations, dislocation arrays possess a large variation of the separation of the partial dislocation pairs in face-centered cubic (fcc) metals. This can be manifested conveniently by an effective stacking fault energy (SFE). The effective SFE of dislocation arrays is described within the elastic theory of dislocations and verified by atomistic simulations. The atomistic modeling results reveal that the general formulae of the effective SFE can give a reasonably satisfactory prediction for all dislocation types, especially for edge dislocation arrays. Furthermore, the predicted variation of the effective SFE is consistent with several previous experiments, in which the measured SFE is not definite, changing with dislocation density. Our approach could provide better understandings of cross-slip and the competition between slip and twinning during plastic deformations in fcc metals.

AIMS To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE. METHODS Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method. RESULTS In Study I, compared with 50 mg acarbose, only 100 mg acarbose had a significantly lower Cmax0-4h than that of sucrose administration alone (7.96 ± 0.83 mmol/L vs 6.78 ± 1.02 mmol/L, P < .05). In Study II, the geometric mean ratios of the test formulation to the reference formulation (both formulations were the branded drug) for FDA PD metrics, ΔCmax0-4h and ΔAUC0-4h , were 0.903 and 0.776, respectively, and the 90% confidence intervals were 67.44-120.90 and 53.65-112.13, respectively. The geometric mean ratios (confidence interval) for possible optimal evaluation PD metrics (Cmax0-2h and AUC0-2h ) were 1.035 (94.23-112.68) and 0.982 (89.28-107.17), respectively. Further, Cmax0-2h and AUC0-2h also met the sensitivity requirements for BE evaluation in Study III. CONCLUSION Considering the mechanisms of action of acarbose, the PD effect was shown to be dose independent during the 2-4 hours postadministration of acarbose. Hence PD metrics based on the serum glucose concentration from 0 to 2 hours (Cmax0-2h and AUC0-2h ) are more sensitive than the FDA-recommended PD metrics for acarbose BE evaluation from 0-4 hours (ΔCmax0-4h and ΔAUC0-4h ). The trial has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800015795, ChiCTR-IIR-17013918, ChiCTR-IIR-17011903). All subjects provided written informed consent before screening.

Humans express two ACAT (acyl-CoA:cholesterol acyltransferase) genes, ACAT1 and ACAT2. ACAT1 is ubiquitously expressed, whereas ACAT2 is primarily expressed in intestinal mucosa and plays an important role in intestinal cholesterol absorption. To investigate the molecular mechanism(s) responsible for the tissue-specific expression of ACAT2, we identified five cis-elements within the human ACAT2 promoter, four for the intestinal-specific transcription factor CDX2 (caudal type homeobox transcription factor 2), and one for the transcription factor HNF1α (hepatocyte nuclear factor 1α). Results of luciferase reporter and electrophoretic mobility shift assays show that CDX2 and HNF1α exert a synergistic effect, enhancing the ACAT2 promoter activity through binding to these cis-elements. In undifferentiated Caco-2 cells, the ACAT2 expression is increased when exogenous CDX2 and/or HNF1α are expressed by co-transfection. In differentiated Caco-2 cells, the ACAT2 expression significantly decreases when the endogenous CDX2 or HNF1α expression is suppressed by using RNAi (RNA interference) technology. The expression levels of CDX2, HNF1α, and ACAT2 are all greatly increased when the Caco-2 cells differentiate to become intestinal-like cells. These results provide a molecular mechanism for the tissue-specific expression of ACAT2 in intestine. In normal adult human liver, CDX2 expression is not detectable and the ACAT2 expression is very low. In the hepatoma cell line HepG2 the CDX2 expression is elevated, accounting for its elevated ACAT2 expression. A high percentage (seven of fourteen) of liver samples from patients affected with hepatocellular carcinoma exhibited elevated ACAT2 expression. Thus, the elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma.

Can aluminum generate deformation twins? Contradictories exist among the experimental results, theoretical predictions, and molecular dynamics simulations. Our first-principles calculations based on the full-potential linearly augmented plane wave method show that the bonding electron density of aluminum gathers at the tetrahedral interstices, and this specific electronic structure is in agreement with the experimental data from quantitative convergent-beam electron diffraction. In terms of this characteristic, the matching between the cohesive energy of local deformation twins with different thickness and global matrix can shed light on deformation twins in aluminum. This study may give a lane to insight into deformation twins in different metals.

To evaluate the month-wise prevalence of subclinical mastitis (SM) and its relations with climatic temperature and humidity, and to provide references for control and prevention of mastitis in dairy cows in Guangdong, China, California mastitis test method was used to determine the monthly prevalence of SM (MPSM, %) of lactating Holstein cows from 11 dairy farms in Guangdong Province, China, including about 516 cows per monthly examination. The average MPSM on a cow and a quarter basis were 30 and 13% respectively, and there was a positive linear correlation between monthly mean air temperature (MT, ?C) and MPSM on a cow basis (r=0.763, P=0.004) or a quarter basis (r=0.577, P=0.049), but there were no correlations between MT and MPSM on a cow or a quarter basis (P>0.05). There was a shift in MPSM trend that the highest MPSM (38.4%) was not for the hottest July with MT at 30.8?C, but for the later September at 27.9?C. The farms need to develop new housing conditions to control cowshed temperatures in the hot season to reduce the mastitis prevalences in the posthot months.

A fuzzy neural network model is proposed to evaluate water quality. The model contains two parts: first, fuzzy mathematics theory is used to standardize the samples; second, the RBF neural network and the BP neural network are used to train the standardized samples. The proposed model was applied to assess the water quality of 16 sections in 9 rivers in the Shaoguan area in 2005. The evaluation result was compared with that of the RBF neural network method and the reported results in the Shaoguan area in 2005. It indicated that the performance of the proposed fuzzy neural network model is practically feasible in the application of water quality assessment and its operation is simple.

The effects of Ga and Ti substitutions for Sn on the Mn spin arrangements in the YMn6Sn6 compound have been investigated by means of X-ray diffraction (XRD), magnetization measurement and Mossbauer spectroscopy. XRD refinement indicates that Ga and Ti atoms prefer to occupy 2d and 2e sites, respectively. Mossbauer spectra indicate incommensurate magnetic structures for the YMn6Sn6, YMn6Sn5.4Ga0.6 and YMn6Sn5.4Ti0.6 compounds. The substitution of Ga for Sn at the 2d sites is found to significantly decrease the turn angle in the Mn–Sn3–Sn2–Sn3–Mn layer and to subsequently increase the net magnetization. On the other hand, the substitution of Ti for Sn at 2e sites increases the turn angles in the Mn–(Y,Sn1)–Mn and Mn–Sn3–Sn2–Sn3–Mn layers, and consequently decreases the exchange coupling of Mn–Mn between different layers. The resulting ferromagnetic and ferrimagnetic behavior, as has been observed for YMn6Sn5.4Ga0.6 and YMn6Sn5.4Ti0.6, respectively, can be explained in terms of these spin interactions.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation. Human ACAT-1 gene contains two promoters (P1 and P7), each located in a different chromosome (1 and 7) (Li, B. L., Li, X. L., Duan, Z. J., Lee, O., Lin, S., Ma, Z. M., Chang, C. C., Yang, X. Y., Park, J. P., Mohandas, T. K., Noll, W., Chan, L., and Chang, T. Y. (1999) J. Biol Chem. 274, 11060-11071). Interferon-gamma (IFN-gamma), a cytokine that exerts many pro-atherosclerotic effects in vivo, causes up-regulation of ACAT-1 mRNA in human blood monocyte-derived macrophages and macrophage-like cells but not in other cell types. To examine the molecular nature of this observation, we identified within the ACAT-1 P1 promoter a 159-base pair core region. This region contains 4 Sp1 elements and an IFN-gamma activated sequence (GAS) that overlaps with the second Sp1 element. In the monocytic cell line THP-1 cell, the combination of IFN-gamma and all-trans-retinoic acid (a known differentiation agent) enhances the ACAT-1 P1 promoter but not the P7 promoter. Additional experiments showed that all-trans-retinoic acid causes large induction of the transcription factor STAT1, while IFN-gamma causes activation of STAT1 such that it binds to the GAS/Sp1 site in the ACAT-1 P1 promoter. Our work provides a molecular mechanism to account for the effect of IFN-gamma in causing transcriptional activation of ACAT-1 in macrophage-like cells.