Transition pathways connecting crystals and quasicrystals.

Due to structural incommensurability, the emergence of a quasicrystal from a crystalline phase represents a challenge to computational physics. Here, the nucleation of quasicrystals is investigated by using an efficient computational method applied to a Landau free-energy functional. Specifically, transition pathways connecting different local minima of the Lifshitz-Petrich model are obtained by using the high-index saddle dynamics. Saddle points on these paths are identified as the critical nuclei of the 6-fold crystals and 12-fold quasicrystals. The results reveal that phase transitions between the crystalline and quasicrystalline phases could follow two possible pathways, corresponding to a one-stage phase transition and a two-stage phase transition involving a metastable lamellar quasicrystalline state, respectively.

Combined preoperative prognostic nutritional index and D-dimer score predicts outcome in colorectal cancer.

BACKGROUND: The prognostic nutritional index (PNI) and D-dimer (DD) levels represent useful prognostic indicators in colorectal cancer (CRC); however, a combination of these indicators, namely, the PNI and DD score (PDS) was less addressed. METHODS: A retrospective study with 183 patients after curative surgery was conducted. Patients were divided into 3 subgroups: PDS 0, decreased PNI and increased DD levels; PDS 1, decreased or increased PNI and DD levels; PDS 2, increased PNI and decreased DD levels. The differences in disease-free survival (DFS) and overall survival (OS) were compared among these subgroups, and risk factors for outcome were determined. RESULTS: A total of 56, 65 and 62 patients were assigned to the PDS 0, 1 and 2 subgroups, respectively. PDS was significant in predicting both the DFS (area under the curve (AUC) = 0.68, P < 0.001) and OS (AUC = 0.74, P < 0.001). PDS 0 patients were more likely to be associated with old age (P = 0.032), laparotomy (P < 0.001), elevated CEA (P = 0.001), T3 + T4 (P = 0.001) and advanced TNM stage (P = 0.031). PDS 0 patients had significantly inferior DFS (log rank = 18.35, P < 0.001) and OS (log rank = 28.34, P < 0.001) than PDS 1 or 2 patients. PDS was identified as an independent risk factor for both DFS (PDS 1: HR = 0.54, 95% CI: 0.30-1.00, P = 0.049; PDS 2: HR = 0.40, 95% CI: 0.20-0.79, P = 0.009) and OS (PDS 1: HR = 0.44, 95% CI: 0.22-0.88, P = 0.020; PDS 2: HR = 0.17, 95% CI: 0.06-0.45, P < 0.001). CONCLUSION: The PDS is a useful prognostic indicator for CRC patients after curative surgery, and PDS 0 patients have inferior survival. Additional future studies are needed to validate these findings.

Identification of metabolites in plasma related to different biological activities of Panax ginseng and American ginseng.

RATIONALE: Panax ginseng (PG) and American ginseng (AMG) are both medicinal plants of the Panax genus in the Acanthopanax family. Although PG and AMG have similar components of ginsenosides, there are many differences of their bioactivities. In this study, the biochemical mechanisms of different bioactivities of PG and AMG were explored by researching the differential metabolites in plasma after administration of each of PG and AMG. METHODS: In order to explore the material basis of differential bioactivities, two groups of mice were administrated orally with PG and AMG, and the method of metabolomics was used to identify the differential metabolites in plasma. Then network pharmacology was used based on the differential metabolites. Afterward, the metabolite-target-pathway network of PG and AMG was constructed; thus the pathways related to different bioactivities were analyzed. RESULTS: Through principal component analysis and orthogonal projections to latent structures discriminant analysis, there were 10 differential metabolites identified in the PG group and 8 differential metabolites identified in the AMG group. Based on network pharmacology, the differential metabolites were classified and related to differential bioactivities of PG and AMG. In the PG group, there were 6 metabolites related to aphrodisiac effect and exciting the nervous system, and 5 metabolites associated with raised blood pressure. In the AMG group, 5 metabolites were classified as having the effect of inhibiting the nervous system, and 6 metabolites were related to antihypertensive effect. CONCLUSIONS: This study explored the material basis of the differential biological activities between PG and AMG, which is significant for the research of PG and AMG use and to promote human health.

Catalytical feature of optical nanoprobes of boron nitride quantum dots in the presence of Cu2+ for the determination of dopamine.

Monitoring the concentration of dopamine (DA) is vital for preventing and diagnosing DA related diseases. In contrast to the traditional sensing methods for DA, in which direct or indirect effects on the optical probes are often recorded, a novel sensing concept is disclosed based on as a result of the in situ formation of polydopamine (PDA) originating from the synergetic effect between boron nitride quantum dots (BNQDs) and Cu2+. In the co-presence of BNQDs and Cu2+, DA was catalytically oxidized to PDA, accompanied by an obvious color change from colorless to brown. In contrast to previous reports, in which BNQDs have been employed as an optical probe, herein, the BNQDs not only acted as the optical energy donor, but also as the catalysts for the formation of PDA. The quenching efficiency resulting from the inner filter effect and the electron transfer between the BNQDs and PDA was directly proportional to the concentration of DA, ranging linearly from 2 to 80 µM with a limit of detection of 0.49 µM. The present system exhibited an outstanding selectivity for DA among other interfering coexisting biomolecules. Furthermore, the practical application of the proposed platform was verified by assaying DA in human plasma samples, and satisfactory recoveries ranging from 101.24% to 111.98% were obtained. With the satisfactory reliability, repeatability and stability, the proposed simple sensor showed significant potential for use in DA detection in other biomedical applications.

Construction of a Pathway Map on a Complicated Energy Landscape.

How do we search for the entire family tree of possible intermediate states, without unwanted random guesses, starting from a stationary state on the energy landscape all the way down to energy minima? Here we introduce a general numerical method that constructs the pathway map, which guides our understanding of how a physical system moves on the energy landscape. The method identifies the transition state between energy minima and the energy barrier associated with such a state. As an example, we solve the Landau-de Gennes energy incorporating the Dirichlet boundary conditions to model a liquid crystal confined in a square box; we illustrate the basic concepts by examining the multiple stationary solutions and the connected pathway maps of the model.

Different absorption and metabolism of ginsenosides after the administration of total ginsenosides and decoction of Panax ginseng.

RATIONALE: Panax ginseng C.A. Meyer (PG), which contains polysaccharides and ginsenosides as the major bioactive components, has been used to promote health and treat diseases for thousands of years in China. Total ginsenosides were extracted from a decoction of Panax ginseng (GD), which included both ginsenosides and polysaccharides, and dissolved in water to obtain a total ginsenosides aqueous solution (TGAS). To study their absorption and metabolism, the pharmacokinetics (PK) and metabolites of ginsenosides in vivo were investigated after the administration of GD and TGAS. METHODS: Rat and mice plasma samples were collected after the administration of GD and TGAS. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry was used with the UNIFI platform to identify metabolites in the plasma sample. The pharmacokinetic parameters were calculated using a noncompartmental method in the Drug and Statistics software package. RESULTS: Thirty ginsenoside metabolites were identified in mice plasma, of which only seven were found in the rat plasma after the administration of GD. The PK of ginsenosides Rb1 , Rc, and Rd were also determined after the oral administration of GD and TGAS and showed significant differences in the pharmacokinetic parameters. CONCLUSIONS: There was no difference in the biotransformation pathways after the oral administration of GD and TGAS, indicating that there was no influence of polysaccharides on the biotransformation of ginsenosides in vivo. However, the pharmacokinetic parameters were different after the administration of GD and TGAS, possibly because of the polysaccharides in GD. This study should be of significance in exploring the basis of PG bioactivities and lays the foundation for the further development of new drugs using PG.

Ginsenoside Rh2 impedes proliferation and migration and induces apoptosis by regulating NF-κB, MAPK, and PI3K/Akt/mTOR signaling pathways in osteosarcoma cells.

Ginsenoside Rh2 is a primary bioactive compound obtained from ginseng that indicated anticancer activities against several malignant tumors. However, previous studies have reported little about the inhibitory effect of Rh2 on osteosarcoma (OS). This study aims to explore whether Rh2 could exert anticancer effects in OS cells and further investigate the proliferation, migration, and apoptosis mechanisms induced by Rh2 in human OS U20S cell line. The viability of U20S cells was obtained by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell migration property was analyzed by wound-healing assay. Apoptosis was visualized using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), 4',6-diamidino-2-phenylindole (DAPI), and annexin V/propidium iodide (PI) staining. Relative protein expressed was confirmed through Western blot analysis. Mitochondrial membrane potential was evaluated by JC-1 staining. In this study, we used broad-spectrum anticancer drug cisplatin (CP) as a positive control. The results indicated that Rh2 remarkably inhibited cell viability of U20S cells in a dose- and time-dependent manner, and suppressed migration. TUNEL, DAPI, annexin V/PI, and JC-1 assay suggested that Rh2 could induce cellular apoptosis. Rh2 could reduce the levels of Bcl-2, caspase 3, and caspase 9, and promote the expression level of Bax in U20S cells. Moreover, Rh2 could induce apoptosis by promoting mitogen-activated protein kinase (MAPK) signaling pathway and inhibit PI3K/Akt/mTOR and nuclear factor-κB (NF-κB) signaling pathway in U20S cells. These findings indicated that Rh2 has an anticancer effect on U20S cells by regulating MAPK, PI3K/Akt/mTOR, and NF-κB signaling pathway.

Guillain-Barre syndrome associated with hemorrhagic fever with renal syndrome in China: a case report.

BACKGROUND: We describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far. CASE PRESENTATIONS: A 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center. CONCLUSIONS: Our case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

Pharmacokinetic and Metabolism Studies of Curculigoside C by UPLC-MS/MS and UPLC-QTOF-MS.

Pharmacokinetic and metabolism studies were carried out on curculigoside C (CC), a natural product with good antioxidant and neuroprotective effects, with the purpose of investigating the effects of the hydroxyl group at C-3' in curculigoside. A rapid and sensitive method with UPLC-MS was developed and fully validated for the first time in the pharmacokinetic analysis for quantification of CC in rat plasma. The assay was linear (R² > 0.9984) over the concentration range of 1⁻2500 ng/mL, with the lower limit of quantification (LLOQ) being 1 ng/mL. The intra-day and inter-day precision (expressed as relative standard deviation, RSD) ranged from 4.10% to 5.51% and 5.24% to 6.81%, respectively. The accuracy (relative error, RE) ranged from -3.28% to 0.56% and -5.83% to -1.44%, respectively. The recoveries ranged from 92.14% to 95.22%. This method was then applied to a pharmacokinetic study of rats after intragastric administration of 15, 30 and 60 mg/kg CC. The results revealed that CC exhibited rapid oral absorption (Tmax = 0.106 h, 0.111 h, and 0.111 h, respectively), high elimination (t1/2 = 2.022 h, 2.061 h, and 2.048 h, respectively) and low absolute bioavailability (2.01, 2.13, and 2.39%, respectively). Furthermore, an investigation on the metabolism of CC was performed by UPLC-QTOF-MSE. Twelve metabolites of CC from plasma, bile, urine and faeces of rats were confirmed. The main metabolic pathways of CC, which involve dehydration, glucosylation, desaturation, formylation, cysteine conjugation, demethylation and sulfonation, were profiled. In conclusion, this research has developed a sensitive quantitative method and demonstrated the metabolism of CC in vivo.

Development and validation of an UPLC-Q/TOF-MS assay for the quantitation of neopanaxadiol in beagle dog plasma: Application to a pharmacokinetic study.

Neopanaxadiol (NPD), the main panaxadiol constituent of Panax ginseng C. A. Meyer (Araliaceae), has been regarded as the active component for the treatment of Alzheimer's disease. However, few references are available about pharmacokinetic evaluation for NPD. Accordingly, a rapid and sensitive method for quantitative analysis of NPD in beagle dog plasma based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry was developed and validated. Analytes were extracted from plasma by liquid-liquid extraction and chromatographic separation was achieved on an Agilent Zorbax Stable Bond C18 column. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions both at m/z 461.4 → 425.4 for NPD and internal standard of panaxadiol. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, were within acceptable ranges and the method was appropriate for multitude sample determination. After oral intake, NPD was slowly absorbed and eliminated from circulatory blood system and corresponding plasma exposure was low. Application of this quantitative method will yield the first pharmacokinetic profile after oral administration of NPD to beagle dog. The information obtained here will be useful to understand the pharmacological effects of NPD.

Portable and visual electrochemical sensor based on the bipolar light emitting diode electrode.

Here we report a novel sensing strategy based on the closed bipolar system, in which we utilize a light emitting diode (LED) to connect a split bipolar electrode (BPE) and generate the luminescent signal in the presence of the target. With this design, we have constructed a BPE array for the quick and high-throughput determination of various electroactive substances with naked eyes. Due to the ultrahigh current efficiency of the closed bipolar system, the sample concentration can be reported by the luminous intensity of the inserted LED without the expensive luminescent agent and instruments. Besides, the stability of the signal is improved because of the electroluminescent property of the LED. To demonstrate the promising applications of the bipolar LED electrode (BP-LED-E), the rapid quantification of four model targets (H2O2, ascorbic acid (AA), glucose, and blood sugar) has been achieved based on different principles.

Structural identification of neopanaxadiol metabolites in rats by ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry.

RATIONALE: Neopanaxadiol (NPD) is one of the major ginsenosides in Panax ginseng C. A. Meyer (Araliaceae) that has been suggested to be a drug candidate against Alzheimer's disease. However, few data are available regarding its metabolism in rats. METHODS: In this study, a method of ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/QTOFMS) was developed to identify major metabolites of NPD in the stomach, intestine, urine and feces of rats, with the aim of determining the main metabolic pathways of NPD in rats after oral administration. RESULTS: UPLC/QTOFMS revealed two metabolites in the stomach of rats, one metabolite in the intestine and two metabolites in feces. One metabolite, named M2, was isolated and purified from rats feces, which was identified as (20S,22S)-dammar-22,25-epoxy-3ß,12ß,20-triol based on extensive NMR spectroscopy and mass spectrometry data. The main metabolites of NPD in rats were the products of epoxidation, dehydrogenation and hydroxylation. NPD was predominantly metabolized by 20,22-double-bond epoxidation and rearrangement to yield an expoxidation product (M2). CONCLUSIONS: Based on the profiles of the metabolites, possible metabolic pathways of NPD in rats were proposed for the first time. This study provides new and available information on the metabolism of NPD, which is indispensable for further research on metabolic pathways of dammarane ginsengenins in vivo.

Tissue distribution and excretion study of neopanaxadiol in rats by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Neopanaxadiol (NPD), a major ginsenoside in Panax ginseng C. A. Meyer (Araliaceae), was reported to have neuroprotective effect. In this study, a method of ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS) was developed and validated for quantitative analysis of NPD in tissues, urine and feces, using liquid-liquid extraction (LLE) to isolate NPD from different biological samples, and chromatographic separation was performed on an Agilent Zorbax Stable Bond C18 (2.1 × 50 mm, 1.8 µm) column with 0.1% formic acid in water and acetonitrile. All standard calibration curves were linear (all r(2) > 0.995) within the test range. After oral administration, NPD was extensively distributed to most of the tissues without long-term accumulation. The higher levels were observed in stomach and intestine, followed by kidney and liver. Approximately 64.56 ± 20.32% of administered dose in feces and 0.0233 ± 0.0356% in urine were found within 96 h, which indicated that the major elimination route was fecal excretion. This analytical method was applied to the study of NPD distribution and excretion in rats after oral intake for the first time. The results we found here are helpful for us to understand the pharmacological effects of NPD, as well as its toxicity.

[Preparation and Determination of Insulin-like Growth Factor I in Deer Antler, Heart and Blood].

OBJECTIVE: To optimize the method for preparation of the insulin-like growth factor I (IGF-I ) in deer antler, and to determine the IGF-I in deer antler, heart and blood. METHODS: Ultrasonic extraction was used to extract IGF-I from different tissues of deer with ammonia-ammonium acetate buffer, followed by ultrafiltration and solid phase extraction to concentrate and purify the samples. At the same time, ethanol precipitation method was carried out in the purification of IGF-I ultrafiltratein deer antler, a parallel test proceeded and radio immune assay (RIA) was set to determine the IGF-I in deer antler, heart and blood. RESULTS: The IGF-I (60.8 ng/g) in deer antler by solid phase extraction was only existed in 30% methanol aqueous solution which was much higher than that (46.1 ng/g) by ethanol precipitation method. The quantities of IGF-I in deer antler, heart and blood were significantly different, it was 61.9 ng/g in antler and 21.9 ng/mL in blood, while there was no IGF-I tested in deer heart. CONCLUSION: Solid phase extraction is superior to ethanol precipitation method in preparing IGF-I in deer antler and it is clear that the IGF-I contained in deer antler is significantly higher than that in deer heart and blood, so it is the best choice to take IGF-I from deer antler.

Revealing excited states of rotational Bose-Einstein condensates.

Rotational Bose-Einstein condensates can exhibit quantized vortices as topological excitations. In this study, the ground and excited states of the rotational Bose-Einstein condensates are systematically studied by calculating the stationary points of the Gross-Pitaevskii energy functional. Various excited states and their connections at different rotational frequencies are revealed in solution landscapes constructed with the constrained high-index saddle dynamics method. Four excitation mechanisms are identified: vortex addition, rearrangement, merging, and splitting. We demonstrate changes in the ground state with increasing rotational frequencies and decipher the evolution of the stability of ground states.

The intramolecular self-assembly of bidesmosidic kalopanaxsaponins.

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR (1H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.

Determination of arecoline in areca nut based on field amplification in capillary electrophoresis coupled with electrochemiluminescence detection.

A sensitive capillary electrophoresis-electrochemiluminescence (CE-ECL) assay with an ionic liquid (IL) was developed for the determination of arecoline in areca nut. The IL, 1-butyl-3-methylimidazolium tetrafluoroborate (BMImBF(4) ), was an effective additive improved not only the separation selectivity but also the detection sensitivity of the analyte. BMImBF(4) in the separation electrolyte made the resistance of the separation buffer much lower than that of the sample solution, which resulted in an enhanced field amplified electrokinetic injection CE. ECL intensity of arecoline is about two times higher than that of the analyte with phosphate-IL buffer system. Resolution between arecoline and other unknown compounds in real samples was improved. Under the optimized conditions (ECL detection at 1.2 V, 16 kV separation voltage, 20 mmol/L phosphate with 10 mmol/L BMImBF(4) buffer at pH 7.50, 5 mmol/L Ru(bpy)(3)(2+) and 50 mmol/L phosphate buffer in the detection reservoir), a detection limit of 5 × 10(-9) mol/L for arecoline was obtained. Relative standard deviations of the ECL intensity and the migration time were 4.51% and 0.72% for arecoline. This method was successfully applied to determination of the amount of arecoline in areca nut within 450 s.

Physical inability rather than depression and cognitive impairment had negative effect on centenarian prognosis: A prospective study with 5-year follow-up.

AIM: Scarce study has involved the effects of physical inability, depression and cognitive impairment on the prognosis of older individuals, especially in Chinese centenarians. This prospective study was designed to investigate the effects with 5-year follow-up in Chinese centenarians. METHODS: According to the list of centenarians provided by Department of Civil Affairs, an household survey was conducted on all centenarians residing in 18 cities and counties of Hainan province. A total of 423 centenarians were followed up, including 84 survival centenarians and 261 dead centenarians, with 78 cases lost to follow-up. RESULTS: Dead centenarians had less females and more physical inability than survival centenarians (P < 0.05 for all). Univariable Cox regression analyses indicated that physical inability [EXP(B): 2.038, 95 % confidence interval (CI): 1.413-2.939], urea nitrogen [EXP(B): 1.116, 95 % CI: 1.039-1.199], and creatinine [EXP(B): 1.006, 95 % CI: 1.001-1.012] had negative effects on the prognosis of centenarians (all P < 0.05). Gender [EXP(B): 0.606, 95 % CI: 0.391-1.940] and albumin [EXP(B): 0.939, 95 % CI: 0.896-0.985] had positive effects on the prognosis of centenarians (all P < 0.05). Multivariable Cox regression analysis indicated that physical inability [EXP(B): 2.148, 95 % CI: 1.454-3.173] and urea nitrogen [EXP(B): 1.114, 95 % CI: 1.020-1.216] had negative effects on the prognosis of centenarians (all P < 0.05). CONCLUSIONS: For Chinese centenarians, this prospective study demonstrated that physical inability rather than depression and cognitive impairment had negative effect on the long-term mortality rate and survival time. This result suggested that in order to improve the prognosis of older adults, it could be mainly achieved by improving physical ability.

ETC-1002 Attenuates Porphyromonas gingivalis Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells via the AMPK/NF-κB Pathway and Exerts Ameliorative Effects in Experimental Periodontitis in Mice.

Background: Clinically, the failure of periodontal therapy stems largely from an inability to control the inflammatory response. Resolution of inflammation is an active, energy-requiring repair process, not merely a passive termination of inflammation. AMP-activated protein kinase (AMPK), a key energy sensor, has been shown to negatively regulate inflammatory signaling pathways. Thus, there is a crucial need for new therapeutic strategies to modulate AMPK and to promote enhanced resolution of inflammation. This study is aimed at investigating the anti-inflammatory effects of ETC-1002 through modulating AMPK in periodontitis. Methods: RAW264.7 cells were infected with Pg-LPS in the presence or absence of ETC-1002, following which the expression levels of proinflammatory cytokines and inflammation signaling-related proteins were evaluated by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. ETC-1002 was applied in a murine model of periodontitis to determine its anti-inflammatory effect in vivo. Histological changes were investigated by hematoxylin and eosin (H&E) staining, the levels of proinflammatory cytokines were detected using immunohistochemistry, and alveolar bone height was measured using micro-CT imaging. Results: ETC-1002 inhibited the production of proinflammatory cytokines, promoted AMPK phosphorylation, and decreased IκBα and NF-κB p65 phosphorylation levels in Pg-LPS-treated RAW264.7 macrophages. The inhibitory effects of ETC-1002 on the production of proinflammatory mediators were significantly abrogated by siRNA-mediated silencing of AMPKα in RAW264.7 cells. In vivo, ETC-1002 inhibited inflammatory cell infiltration, the expression of proinflammatory cytokines, and the inflammation-mediated destruction of alveolar bone in mice with experimental periodontitis. The anti-inflammatory effect of ETC-1002 in the periodontium could be reversed by the administration of Compound C, an AMPK inhibitor. Conclusions: ETC-1002 exerts anti-inflammatory effects in Pg-LPS-treated RAW264.7 cells via the AMPK/NF-κB pathway in vitro and inhibits the progress of experimental periodontitis in mice in an AMPK signaling-dependent manner in vivo. These results provide evidence for the beneficial effects of ETC-1002 in the treatment of periodontitis.

Solution landscapes of the diblock copolymer-homopolymer model under two-dimensional confinement.

We investigate the solution landscapes of the confined diblock copolymer and homopolymer in two-dimensional domain by using the extended Ohta-Kawasaki model. The projection saddle dynamics method is developed to compute the saddle points with mass conservation and construct the solution landscape by coupling with downward and upward search algorithms. A variety of stationary solutions are identified and classified in the solution landscape, including Flower class, Mosaic class, Core-shell class, and Tai-chi class. The relationships between different stable states are shown by either transition pathways connected by index-1 saddle points or dynamical pathways connected by a high-index saddle point. The solution landscapes also demonstrate the symmetry-breaking phenomena, in which more solutions with high symmetry are found when the domain size increases.