Discovery of quality markers of Phyllanthus emblica by integrating chromatographic fingerprint, serum pharmacochemistry and network pharmacology.

Phyllanthus emblica (P. emblica) is a vital medicinal plant with both medical and edible values. In the quality standard of P. emblica listed by the Chinese Pharmacopoeia, gallic acid is used as the index component for the content determination. However, a large number of tannin components can be decomposed into gallic acid during its refluxing extraction process, thus affecting the accuracy and specificity of the content determination. Thus, the index component used for the quality control needs to be further determined. In this study, the quality markers of P. emblica was specified by integrating chromatographic fingerprint, serum pharmacochemistry and network pharmacology. The chromatographic fingerprint of 18 batches of P. emblica samples were established by ultra-high-performance liquid chromatography (UPLC), and 8 differential components causing quality fluctuation were identified by chemometric analysis and UPLC-Q-TOF/MS analysis. Afterwards, 14 prototype migration components absorbed into the blood after gavage administration to rats were identified by UPLC-Q-TOF/MS analysis. Subsequently, a network pharmacology approach was used to construct the component-target-disease-pathway network, resulting in the identification of 22 components responsible for efficacy of P. emblica. Finally, by integrating the above results, ellagic acid was screened out as one of the Q-markers and could be employed as a quantitative component of P. emblica to improve the quality standard. The strategy is also informative for discovering Q-markers of other TCMs.

Current status of novel biologics and small molecule drugs in the individualized treatment of inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) are rapidly evolving with the development of biologics and small molecule drugs (SMDs). However, these drugs are not guaranteed to be effective in all patients, and a "ceiling effect" of biologic monotherapy may occur. This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses. Thus, the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs. In addition, combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD, which theoretically has multidimensional anti-inflammatory potential. Based on the current evidence available for IBD, dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic trea-tments or who have extraintestinal manifestation. Additionally, identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission. In this review, we sum-marize the newly developed biologics and SMDs and the current status of bio-logics/SMDs to highlight the development of individualized treatment in IBD.

Reinforcement Learning (RL)-Based Energy Efficient Resource Allocation for Energy Harvesting-Powered Wireless Body Area Network.

Wireless body area networks (WBANs) have attracted great attention from both industry and academia as a promising technology for continuous monitoring of physiological signals of the human body. As the sensors in WBANs are typically battery-driven and inconvenient to recharge, an energy efficient resource allocation scheme is essential to prolong the lifetime of the networks, while guaranteeing the rigid requirements of quality of service (QoS) of the WBANs in nature. As a possible alternative solution to address the energy efficiency problem, energy harvesting (EH) technology with the capability of harvesting energy from ambient sources can potentially reduce the dependence on the battery supply. Consequently, in this paper, we investigate the resource allocation problem for EH-powered WBANs (EH-WBANs). Our goal is to maximize the energy efficiency of the EH-WBANs with the joint consideration of transmission mode, relay selection, allocated time slot, transmission power, and the energy constraint of each sensor. In view of the characteristic of the EH-WBANs, we formulate the energy efficiency problem as a discrete-time and finite-state Markov decision process (DFMDP), in which allocation strategy decisions are made by a hub that does not have complete and global network information. Owing to the complexity of the problem, we propose a modified Q-learning (QL) algorithm to obtain the optimal allocation strategy. The numerical results validate the effectiveness of the proposed scheme as well as the low computation complexity of the proposed modified Q-learning (QL) algorithm.

Uniform Surface Modification of Li2ZnTi3O8 by Liquated Na2MoO4 To Boost Electrochemical Performance.

Poor ionic and electronic conductivities are the key issues to affect the electrochemical performance of Li2ZnTi3O8 (LZTO). In view of the water solubility, low melting point, good electrical conductivity, and wettability to LZTO, Na2MoO4 (NMO) was first selected to modify LZTO via simply mixing LZTO in NMO water solution followed by calcining the dried mixture at 750 °C for 5 h. The electrochemical performance of LZTO could be enhanced by adjusting the content of NMO, and the modified LZTO with 2 wt % NMO exhibited the most excellent rate capabilities (achieving lithiation capacities of 225.1, 207.2, 187.1, and 161.3 mAh g-1 at 200, 400, 800, and 1600 mA g-1, respectively) as well as outstanding long-term cycling stability (delivering a lithiation capacity of 229.0 mAh g-1 for 400 cycles at 500 mA g-1). Structure and composition characterizations together with electrochemical impedance spectra analysis demonstrate that the molten NMO at the sintering temperature of 750 °C is beneficial to diffuse into the LZTO lattices near the surface of LZTO particles to yield uniform modification layer, simultaneously ameliorating the electronic and ionic conductivities of LZTO, and thus is responsible for the enhanced electrochemical performance of LZTO. First-principles calculations further verify the substitution of Mo6+ for Zn2+ to realize doping in LZTO. The work provides a new route for designing uniform surface modification at low temperature, and the modification by NMO could be extended to other electrode materials to enhance the electrochemical performance.

Correction: Two-Level Scheduling for Video Transmission over Downlink OFDMA Networks.

[This corrects the article DOI: 10.1371/journal.pone.0148625.].

Two-Level Scheduling for Video Transmission over Downlink OFDMA Networks.

This paper presents a two-level scheduling scheme for video transmission over downlink orthogonal frequency-division multiple access (OFDMA) networks. It aims to maximize the aggregate quality of the video users subject to the playback delay and resource constraints, by exploiting the multiuser diversity and the video characteristics. The upper level schedules the transmission of video packets among multiple users based on an overall target bit-error-rate (BER), the importance level of packet and resource consumption efficiency factor. Instead, the lower level renders unequal error protection (UEP) in terms of target BER among the scheduled packets by solving a weighted sum distortion minimization problem, where each user weight reflects the total importance level of the packets that has been scheduled for that user. Frequency-selective power is then water-filled over all the assigned subcarriers in order to leverage the potential channel coding gain. Realistic simulation results demonstrate that the proposed scheme significantly outperforms the state-of-the-art scheduling scheme by up to 6.8 dB in terms of peak-signal-to-noise-ratio (PSNR). Further test evaluates the suitability of equal power allocation which is the common assumption in the literature.

[Effect of autologous peripheral blood stem cell transplantation in 13 patients with AML1/ETO (+) acute myeloid leukemia].

This study was purposed to analyse the clinical efficacy of autologous peripheral blood stem cell transplantation (APBSCT) in 13 Patients with AML1/ETO (+) acute myeloid leukemia, and to evaluate the role of quantitative detecting the AML1/ETO gene in treatment of AML patients. A total of 13 patients with AML1/ETO (+) acute myeloid leukemia treated with APBSCT from August 2007 to November 2012 were retrospectively analyzed. The median follow-up time was 26 (7.8-75.8)months. Kaplan-Meier analysis was used to calculate the overall survival (OS), leukemia-free survival (LFS) and cumulative relapse rate (RR). Log rank method was used to perform univariate analysis. The results showed that the 3 year-OS, LFS, and RR were (70.5 ± 15.3)%, (51.3 ± 16.7)%, 48.7%, respectively. The AML1/ETO expression level in 4 cases out of 5 relapsed patients was quantified during and after therapy, and the result showed that AML1/ETO expression level significantly increased before morphological relapse. In univariate analysis, there was no statistic significance in terms of age, sex, count of white blood cells at diagnosis, interval from diagnosis to transplantation, count of MNC for infusion. It is concluded that APBSCT has good therapeutic effect on AML1/ETO (+) AML, and regular quantitative monitoring of AML1/ETO expression level can predict early recurrence. Allogeneic hematopoietic stem cell transplantation after relapse may contribute to obtain opportunity to achieve the long-term survival for intermediate and high risk patients.

Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.