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Epidemiological studies suggested that periodontitis is a risk factor for pregnancy complications including preterm birth. Porphyromonas gingivalis, a vital periodontal pathogen found in amniotic fluid and intact membranes of women who deliver preterm low birth weight infants, is thought to contribute to preterm labor. However, molecular and cellular interactions between P. gingivalis and placental cells are not clear. In this study, we investigated the effect of P. gingivalis on human extravillous trophoblasts and observed that it triggered apoptosis and inflammation and that Akt was activated in this process. In addition, when Akt activation was inhibited, apoptosis and inflammation was significantly increased. Thus, P. gingivalis infection contributes to preterm low birth weight infants by triggering excessive inflammation and increasing apoptosis in trophoblasts and that the Phosphatidylinositol 3-Kinase/Akt signaling pathway is involved in the regulation of Pg-induced apoptosis and inflammation.

Objective: The aim of this study was to design an ultrasonic method to measure the adductor pollicis muscle thickness (APMT) of stable chronic obstructive pulmonary disease (COPD) patients. We also tested handgrip strength (HGS) to study the relationship between APMT and HGS in COPD patients. Method: 40 Stage I ~ II COPD out-patients and 20 non-COPD controls participated in the study. The ultrasound measurements of APMT were made with the subjects sitting with his or her hand lying on the knee, and put the 10 MHz probe on the triangle formed by the extension of the thumb and index finger. The ultrasonic APMT measurements start at the tip of the dorsal interosseous muscle, obliquely to the contralateral adductor pollicis fascia, the measuring lines overlapping to the path between champing points of caliper. The average of 3 consecutive measurements was considered to be the muscle thickness. The kappa coefficient was applied to assess the degree of the inter- and intra-observer agreement. Results: Ultrasound can be used to measure the thickness of adductor pollicis muscle conveniently. The APMT of dominant hand of men were 9.78 ± 0.34 mm, and women were 7.37 ± 0.48 mm in our 40 Stage I ~ II COPD out-patients. There were significant differences in APMT and HGS by genders. The APMT had a significant positive correlation with HGS (r = 0.676; P < 0.0001) in our COPD patients. The inter- and intra-observer reliability of ultrasonic APMT measurement was satisfactory. Conclusion: Ultrasonic adductor pollicis muscle thickness measurement is a new way and with excellent inter- and intra-observer reliability; it can be used as a new clinical metrology of nutritional status research and upper limb muscle function evaluation. Funding Statement: This work was supported by grants from Shanghai Municipal Health Commission (No. 201740227) and Shanghai University of Medical & Health Sciences (No. E1-0200-18-201116). This work was also supported by the National Natural Science Foundation of China (No. 81701547) and the Beijing Medical and Health Foundation (No. YWJKJJHKYJJ-F2187E). Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: The project was approved by the Ethics and Research Committee of our institution (number 2015ky134).

In recent years, more than 50 tyrosine kinase inhibitors (TKIs) was indicated against numerous cancers, especially outstanding advantages in the treatment of non-small cell lung cancer (NSCLC), and several studies have shown that therapeutic drug monitoring (TDM) of TKIs can improve treatment efficacy and safety. The present study aimed to develop and validate a LC-MS/MS method for the TDM of 12 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, icotinib, osimertinib, crizotinib, ceritinib, alectinib, dabrafenib, trametinib, anlotinib) in patients with NSCLC. The analytes of interest and internal standard were extracted from human plasma. Salting-out assisted liquid–liquid extraction (SALLE) with 5 M ammonium acetate solution was optimized for method validation and compared to simple protein precipitation (PPT). Chromatographic separation was conducted on Waters X bridge C18 column (100 × 4.6 mm, 3.5 μm) using a gradient elution of acetonitrile/5mM ammonium acetate in pure water with 0.1% (v/v) formic acid at 40 °C within 6 min. The total flow was maintained at 1 mL/min, 30% of the post column flow was split into the mass spectrometer and the rest to waste via a 3-way tee. The mass analysis was performed by positive ion electrospray ionization (ESI) in multiple-reaction monitoring (MRM) mode. The assay was validated based on the guidelines on bioanalytical methods by FDA. This quantification method was proved to be satisfactory in selectivity, accuracy, precision, linearity (r2 > 0.995), recovery, matrix effect and stability and the accuracy was further assessed in plasma with a degree of hemolysis of 4%. The described method to simultaneously quantify the 12 selected anticancer drugs in human plasma was successfully validated and applied to routine TDM of gefitinib, erlotinib, icotinib, osimertinib, crizotinib and anlotinib in cancer patients. TKIs plasma monitoring helps to individualize dose adjustment and manage adverse effects in NSCLC patients.

Water Saving Management Contract (WSMC) is believed as an efficient water-saving model and developed in recent years. However, because the high upfront investment cost and great uncertainty of WSMC, the static evaluation methods have defects in evaluating the return on investment of WSMC projects. Real option theory makes up for these defects and is applied in this paper with the expectation to evaluate the uncertainty of a Shared WSMC project and the economic feasibility of investing in the project. First, a new expression of volatility is presented based on the characteristics of Shared WSMC projects. The volatility contains uncertainties in water price, the amount of water-saving, waterborne fee, and operating & maintenance cost simultaneously. Then, it is assumed that the water saving service company is entitled options to abandon and expand the Shared WSMC project during the contract period. Based on the existing model, the exercise prices of the two options are improved. Furthermore, the real option value (ROV) of a Shared WSMC project is solved using the binomial tree option pricing model, and the economic feasibility of the project is comprehensively evaluated by combining with the static net present value and ROV organically. Finally, the Shared WSMC project of the Hebei University of Engineering in China is studied to verify the validity of the proposed method. The obtained results indicate that the economic value of the Shared WSMC project is expanded by the ROV, which means that additional value can be gained through flexible strategies and management in the context of uncertainty. Besides, the additional economic benefits of the two options vary significantly for different Shared WSMC projects. Expand option is particularly essential when Shared WSMC projects with a considerable return on investment. Conversely, the abandon option should be taken seriously. Especially when both options are considered together, the additional economic benefits are sub-additive.

Background Melanocyte stem cells (McSCs) are the origin of melanocytes that are periodically refreshed in skin and hair follicle. Previously, we reported that Wnt3a could promote melanogenesis, but the mechanism of McSCs activation remains unclear. Objective We aimed to illustrate the roles of Wnt/s-catenin signaling pathway during McSC activation. Methods Adenovirus-mediated overexpression of Wnt3a and Wnt10b were used. In vitro experiments were performed on the immortalized melanocyte progenitor cell line iMC23, wheres in vivo experiments were performed in Dct-LacZ mice. Immunofluorescence and western blot were used to determine the protein expression. Results Wnt3a promotes the differentiation and melanogenesis of iMC23, by activating Wnt/β-catenin signaling pathway. Wnt3a induces hair follicle regeneration and McSC activation. Detailed analysis indicats that Wnt3a activated Wnt/β-catenin signaling pathway, thus promoting the differentiation of McSCs during this process. Wnt10b, another canonical Wnt signaling ligand, induces hair follicle regeneration and McSC activation as well. Conclusion Wnt/β-catenin signaling pathway activates McSCs both in vitro and in vivo .

The conductive polymers PEDOT:PSS coated Li1.20[Mn0.53Ni0.13Co0.13Nb0.01]O2 cathode materials were synthesized via using the sol-gel method, followed by the wet solution process. And the X-ray diffraction (XRD), Rietveld refinement, Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) were adopted to investigate the morphology and constituents of as-prepared cathode materials. The results demonstrated that a PEDOT:PSS layer was uniformly distributed on the surface of bulk Li1.20Mn0.54Ni0.13Co0.13O2 with Nb5+ doping successfully. And the PEDOT:PSS surface coating and Nb5+ doping modifications showed a significant improvement on the electrochemical properties of cathode. In particular, the 2 wt% PEDOT:PSS coated Li1.20[Mn0.53Ni0.13Co0.13Nb0.01]O2 delivered a supernal discharge capacity of 145.6 mAhg−1 at 5C high rate and retained a high capacity retention of 90.8% after 200 cycles at 45 °C, which were more superior than those of the pristine cathode (90.2 mAhg−1 and 80.7%). The enhanced electrochemical properties could be attributed to the facilitation of Lithium ions diffusion, the lower cation mixing and restriction of the side reactions between cathode surfaces with electrolyte by the Nb5+ doping and PEDOT:PSS coating.

In this paper new binary organogels based on glutamic acid derivatives and acids with different molecular skeletons were designed and prepared. Their gelation behaviors in single or mixed solvents were tested as novel low-molecular-mass organic gelators. The experimental data showed that the solvents and molecular skeletons played a crucial role in regulating the gelation behaviors and fabrication of nanostructures. Suitable single solvents or volume ratios in ethanol/water mixed solvents seemed more favorable for the formation of supramolecular gels due to cooperation of multi-intermolecular weak forces. Rational assembly modes in organogels were proposed and discussed. The present work may give some insight to design and character new versatile organogelators and soft materials with special molecular structures.

Hair follicles periodically undergo regeneration. The balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. We previously reported that Wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. To unveil the roles of Wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. On the basis of this model, we found that Wnt10b could induce the biological switch of hair follicles from telogen to anagen when overexpressed in the skin. The induced hair follicles expressed structure markers and could cycle normally into catagen. Conversely, anagen onset was abrogated by the knockdown of Wnt10b with small interfering RNA (siRNA). The Wnt10b aberrant expression data suggest that it is one of the activators of hair follicle regeneration. The β-catenin protein is translocated to the nucleus in Wnt10b-induced hair follicles. The biological effects of Wnt10b were abrogated when β-catenin expression was downregulated with siRNA. These data revealed that Wnt10b might induce hair follicle regeneration in vivo via the enhanced activation of the canonical Wnt signaling pathway. To our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide potential therapeutic targets for hair follicle–related diseases.

To demonstrate ultrasound contrast agents to be important potentiators of high-intensity focused ultrasound (HIFU), we prospectively assessed the effectiveness of HIFU combined with nanoscale ultrasound contrast agents for the treatment of breast VX2 tumors in rabbits. We found that the change of grayscale value in the target area in the HIFU+nanobubble group was significantly higher than that in the HIFU+phosphate-buffered saline (PBS) group after irradiation (P

Although the importance of Wnt3a in melanocyte development has been well recognized, the effect of Wnt3a in normal HF melanocytes has not been clearly elucidated yet. Thus, we sought to examine the presence and location of Wnt3a in HF during hair cycle. By using melanocyte-targeted Dct-LacZ transgenic mice, we found that Wnt3a signaling is activated in mouse HF melanocytes during anagen of hair cycle. To further explore the potential functions of Wnt3a in mouse melanocytes, we infected melan-a cells with AdWnt3a to serve as the production source of Wnt3a protein. We demonstrated that Wnt3a promoted melanogenesis through upregulation of MITF and its downstream genes, tyrosinase and TRP1, in melanocytes. In vivo, AdWnt3a rescued the effects of AdsimMITF on HF melanocytes and promoted melanin synthesis. Our results suggest that Wnt3a plays an important role in mouse HF melanocytes homeostasis.

Uncertain statistics is a methodology for collecting and interpreting experts’ experimental data by using uncertainty theory. Based on empirical uncertainty distributions, this paper will present a statistical method of uncertain hypothesis testing to detect whether two uncertainty distributions are equal.