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Purpose The microRNA (miRNA) profile changes in the tumor-associated macrophages. However, the role of miR-106b-5p in the glioblastoma-associated macrophages is poorly understood. Materials and methods In our study, miR-106b-5p and M2 macrophage markers were detected by qRT-PCR and Western blotting in THP1 cells, with the conditioned medium from U251 cells or M2 macrophages in response to IL-4 stimulation and M1 macrophages stimulated by LPS and IFN-γ. IFN regulatory factor (IRF1) was identified as a target of miR-106b-5p in the glioma infiltrating macrophages by luciferase reporter assay. The molecular mechanisms involved in the miR-106b-5p-mediated regulation of M2 polarization were clarified by shRNA knockdown assay. Results Our results showed miR-106b-5p expression was upregulated in glioma-infiltrating macrophages. miR-106b-5p regulated M2 polarization of glioma infiltrating macrophages and enhanced the growth of glioma-infiltrating macrophages. IRF1 was identified as a target of miR-106b-5p. Furthermore, miR-106b-5p inhibited IRF1 expression by targeting IRF1/IFN-β pathway to promote M2 polarization of macrophages. Conclusion miR-106b-5p may inhibit IRF1/IFN-β signaling to promote M2 macrophage polarization of glioblastoma, and it may become a novel target for the treatment of glioblastoma.

Wang M, Wu Q, Fang M, Huang W, Zhu H. Onco Targets Ther. 2019;12:9513–9525. The Editor and Publisher of OncoTargets and Therapy wish to issue an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Background Accumulating evidences suggest that microRNAs (miRNAs) play key roles in mediating glioblastoma progression. Decreased expression of miR-152-3p was reported in several cancer types including glioblastoma. Methods The sensitivity of glioblastoma cells to cisplatin was assessed by the cell counting kit-8 assay and flow cytometry analysis. The expression of miR-152-3p was determined by RT-qPCR method. Bioinformatic analysis, dual luciferase reporter assay and Western blot were used to explore the target gene of miR-152-3p. The association between miR-152-3p and SOS1 was confirmed in glioblastoma tissues by Pearson correlation analysis. Results In the current study, we discovered that overexpression of miR-152-3p increased cisplatin sensitivity while inhibition of miR-152-3p decreased cisplatin sensitivity in glioblastoma cells (T98G and U87). In addition, miR-152-3p augmented cell apoptosis induced by cisplatin treatment. It was further predicted and validated that SOS1, a protein involved in regulating chemotherapy sensitivity, was a direct target gene of miR-152-3p. SOS1 was proven to suppress the cytotoxic effect of cisplatin in glioblastoma. Transfection of recombinant SOS1 could effectively reverse the increased cisplatin sensitivity induced by miR-152-3p overexpression in T98G. Furthermore, overexpression of SOS1 reduced the percentage of apoptotic cells increased by miR-152-3p mimic in the presence of cisplatin in T98G. More importantly, a significant negative correlation between miR-152-3p levels and SOS1 levels was observed in glioblastoma tissues collected from 40 patients. Conclusion Our study identified miR-152-3p as a chemotherapy sensitizer in glioblastoma.

Two new triterpene saponins, namely notoginsenoside Ng5 (1) and notoginsenoside Ng6 (2) were isolated from the leaves of Panax notoginseng, along with five known ones. Their structures were determined by chemical methods, NMR and X-ray experiments. The absolute configuration of compound 3 with four sugar units was confirmed by single crystal X-ray analysis. Compounds 2–4 and 6 inhibited PC12 cell damage induced by serum deprivation, and increased cell viability from 58.7 ± 6.7% to 66.7 ± 4.5%, 76.1 ± 6.1%, 64.7 ± 5.2% and 67.2 ± 5.0% at 10 μM, respectively.

“May Fourth” has long been considered a turning point for modern China, resulting in continuous heated discussion on the topic since the 1920s. These discussions not only reexamine culture but also...

To investigate the effect of varying the light intensity on the photosynthate distribution, cherry tomato (Solanum lycopersicum L.) seedlings were grown under different light intensities. It was fo...

The MinE protein plays an important role in plastid division. In this study, the MinE gene was isolated from the cassava (Manihot esculenta Crantz) genome. We isolated high quality and quantity protoplasts and succeed in performing the transient expression of the GFP-fused Manihot esculenta MinE (MeMinE) protein in cassava mesophyll protoplasts. The transient expression of MeMinE-GFP in cassava protoplasts showed that the MeMinE protein was located in the chloroplast. Due to the abnormal division of chloroplasts, overexpression of MeMinE proteins in cassava mesophyll protoplasts could result in fewer and smaller chloroplasts. Overexpression of MeMinE proteins also showed abnormal cell division characteristics and minicell occurrence in Escherichia coli caused by aberrant septation events in the cell poles. MeMinE proteins function in cassava chloroplasts and Escherichia coli. The MinE protein plays an important role in plastid division.

Cassava is a tropical crop known for its starchy root and excellent properties. Considering that starch biosynthesis in the amyloplast is affected by its division, it appears conceivable that the regulation of plastid division plays an important role in starch accumulation. As a member of the Min system genes, MinD participated in the spatial regulation of the position of the plastid division site.In our studies, sequence analysis and phylogenetic analysis showed that MeMinD has been highly conserved during the evolutionary process. Subcellular localisation indicated that MeMinD carries a chloroplast transit peptide and was localised in the chloroplast. Overexpression of MeMinD resulted in division site misplacement and filamentous formation in E. coli, indicating that MeMinD protein was functional across species. MeMinD exhibited different spatial and temporal expression patterns which was highly expressed in the source compared to that in the sink organ.

Jen-Wu Huang,1,2 Yi-Ying Lin,2,3 Nai-Yuan Wu,4 Yu-Chun Chen5–7 1Department of Surgery, National Yang-Ming University Hospital, National Yang-Ming University, Yilan, Taiwan; 2Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Pediatrics, Heping Fuyou Branch, Taipei City Hospital, Taipei, Taiwan; 4Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan; 5Department of Medical Research and Education, National Yang-Ming University Hospital, Yilan, Taiwan; 6Faculty of Medicine and School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Institute of Hospital and Health Care Administration, School of Medicine, National Yang-Ming University, Taipei, Taiwan Objective: This study aimed to investigate the mortality rate after falls of rural and non-rural older people and to explore the risk factors of mortality after falls among older people. Patients and methods: This population-based case–control study identified two groups from a nationwide claim database (National Health Insurance Research Database in Taiwan): a rural group and a non-rural group, which included 3,897 and 5,541 older people, respectively, who were hospitalized for accidental falls (The International Classification of Diseases, Ninth Revision, Clinical Modification: E880–E888) during 2006–2009. Both groups were followed up for 4 years after falls. Four-year cumulative all-cause mortality rate after falls was calculated, and the demographic factor, comorbidity, and medications were considered as the potential risk factors of mortality after falls. Results: The rural group had a significantly higher frequency of fall-related hospitalizations (7.4% vs 4.3%, P

EDITOR’S ABSTRACTIn this article, Huang discusses the process whereby the concept of democracy was translated into the Chinese context during the transitional period of modern China (1895–1925). He asserts that while democracy was rooted in a pessimistic conception of human nature and epistemology in the West, Chinese intellectuals rather tended toward an optimistic view of both, a fact that brought them closer to the Rousseauian tradition of democratic thought. However, Huang also sees signs of a Millianism with Chinese characteristics in the thought of Yan Fu and Liang Qichao.

In this article, Huang stresses the important role played by the Chinese cultural context in the historical process of translation of Western concepts. Huang exemplifies this point through an analy...

In this article, Huang provides a historical account of the way intellectuals have conceptualized democracy, representative assemblies, and political parties from the end of the Qing dynasty to the...

In this study, the authors evaluated how much price changes in food and energy – two basic living expenditures competing for consumers’ budgets – would affect consumer welfare. We first estimated a US complete demand system to quantify the interdependent demand relationships among 11 categories of consumption expenditures. Among the estimates, the own price elasticities of both food and energy are relatively inelastic, a finding that explains the dynamics of the recent soaring food and energy prices. The estimated demand elasticities were then incorporated into the measurement of Hicksian compensating variation to analyse the consumer welfare effects of price changes in food and energy. The results indicated that an increase in food and energy prices would increase compensated expenditures or incur a substantial consumer welfare loss, creating an especially heavy burden for low income households.

Due to the rapid growth and development of technology, the plastic cash has been a new exchange tool. However, the tradition coin is still a popular exchange tool. This study used the psychophysical method of constants stimuli to determine the difference threshold and Weber Fraction of diameter size of NT coins. A total of 30 college students (15 males, 15 females) participated in the laboratory experiment. A standard diameter size (23 mm) and eight comparison diameter sizes (18, 19, 20, 21, 22, 24, 25, 26, 27, 28 mm) of coins were used. A constant Weber Fraction of about 0.04 and a mean difference threshold of about 0.918 mm at diameter size of 23 mm were found. The effect of gender on the size discriminability was not significant. Furthermore, the diameter size discriminability of NT$20 was confused easily with NT$10. The information obtained in this study will help in improving the design of NT coins.

This paper demonstrates a fuzzy sliding mode control (FSMC) scheme for a static reactive power compensator (static VAR compensator or SVC) to improve the damping of a synchronous generator. A robust sliding regime is derived to guarantee the stability of the proposed FSMC under parameter uncertainties. Two types of FSMC, the fuzzy switching gain compensation and the fuzzy control signal compensation, are recommended to regulate the reactive power of the SVC. A synchronous generator system with the proposed FSMC-SVC has been studied and its dynamic responses are simulated. The results show that the suggested FSMC scheme possesses the advantages of fuzzy control and sliding mode control, e.g. insensitivity to parameter variations and load disturbances. Note that the dynamic performance of the synchronous machine system can be improved dramatically over a wide range of operating conditions. Furthermore, for simplification of practical implementation, the reducing switches (or local feedback) control is adopted.

Studies of lung tissues and bronchoalveolar lavage specimens from patients with pneumonia have led some investigators to propose that human herpesvirus 6 (HHV-6) can cause pneumonia. As the etiologic role of HHV-6 in pneumonia remains poorly defined, cases of pneumonia that are associated with pulmonary HHV-6 infection are best described as HHV-6-associated pneumonias. The clinical spectrum of HHV-6-associated pneumonia encompasses both mild and severe cases. Most cases reported so far occurred in immunosuppressed individuals following bone marrow transplantation or HIV infection. Some studies have identified coinfections with HHV-6 and other viruses in a surprising number of HHV-6-associated pneumonias. Although no systematic evaluation of treatment regimens is available at this time, coincidental administration of antiviral drugs did not generally result in clinical improvement. Controlled, prospective studies are needed to understand the clinical presentation, clinical course, etiology, diagnosis and treatment of HHV-6-associated pneumonias.

A new data treatment method for the linear nonisothermal accelerated kinetic study is presented and discussed. Besides being simple and straightforward, the method involves no assumptions. Important kinetic parameters can be rapidly determined for stability assessment purpose. When this method is compared with two other data treatment methods, while being able to provide equally satisfactory results, this new method offers the advantages of placing equal weights on all data points and requiring only a single numerical integration.

The Food and Drug Administration (FDA) is proposing that a satisfactory three-month stability testing of a drug product at 37 to 40 °C and 75% or higher relative humidity can be employed to project a tentative expiry date of two years from the date of manufacture. This proposal is theoretically analyzed and its limitation is established. A successful projection of the expiry date according to FDA's proposal depends on the drug level at the end of the accelerated stability testing, the activation energy, and the temperature of the accelerated condition and the normal storage condition. The applicability of this method in assessing the stability characteristics of pharmaceutical formulations in the development process is discussed.

The errors involved in the estimation of the activation energy of the drug degradation and the projected shelf life of a drug product when employing an incorrect kinetic order in the accelerated stability test were analyzed. The activation energy of a zero order degradation and the projected shelf life of a drug product are overestimated when the kinetic data are treated in first order fashion. The overestimation in the activation energy increases with the temperature range of the accelerated test and the instability of the drug. The over-estimation in the projected shelf life increases with the activation energy and increases as the normal

Borrowing the mathematics used in the nonisothermal kinetic method, a new and simpler mathematical treatment of the concept of the Equilibrium Temperature Time Equivalents (ETTE) is presented. The effect of the ETTE in the pharmaceutical product stability assessment is discussed. The analysis shows that due to the stability characteristics of most drug candidates, the ETTE has very little effect on the stability data treatment.

The mechanism of a molecular-scale entrapment of cationic drug by negatively charged latices was investigated using the measurement of zeta potential as a physical/analytical tool. It was found that as the amount of the drug was increased the zeta potential of latex particles decreased. The simultaneous presence of a dicarboxylic acid with the drug increased the zeta potential. Entrapment products were prepared using diluted latices, a cationic drug (Chlorpromazine hydrochloride), and an entrapment facilitator (succinic acid). The dissolution of the drug from the products was found to be first order in all cases. The data showed that (a) the smaller the particle size the faster the release rate, (b) the order of combination (latex to drug or vice versa) did not affect the release rate, and (c) the use of entrapment facilitator (a dicarboxylic acid), did not change the release rate but increased the amount of drug entrapped. The agreement of the first order dissolution and the first order desorptio...

The establishment of the expiration date of pharmaceutical product through the statistical treatment of stability data is discussed in detail for both the stability studies under normal storage conditions and accelerated storage conditions.

A non-isothermal kinetic study allows the determination of the important kinetic parameters in a single experiment and thus is useful for the quick assessment of stability characteristics of the pharmaceutical prototypes during the development stage. The applicability and limitations of two non-isothermal accelerated kinetic methods in the pharmaceutical product development are discussed. Both methods are simple and no sophisticated calculation is necessary. These methods, however, fail to provide a unique reaction order for the pharmaceutically acceptable systems. The method is applicable only to those systems which obey the Arrhenius relationship.

The use of a class of antimicrobial agents, the bisbiguanides, in oral hygiene and their involvement in the formation of teeth staining are reviewed. Particular attention is placed on a discussion of the mechanism of bisbiguanide-induced staining from a molecular level and the approaches taken to resolve this staining problem.

A previous publication (1) analyzed a statement originated from the Food and Drug Administration (FDA) that a drug product which is stable for three months at 37–40° and 75% or higher relative humidity can be given a tentative expiry period of two years from the date of manufacture. Conditions which can be uesd to make a successful projection using such a proposal have been established. These conditions are applicable only to pharmaceutical systems which do not contain an overage. The theoretical discussion is extended in this communication to analyze the effect of the overage on the proposed projection of the expiry period. The analysis shows that the inclusion of the overage lowers the threshold activation energy needed to satisfy the FDA's proposal

The effect of the temperature fluctuation in a nominal isothermal stability study is theoretically analyzed using hypothesized temperature-time functions. It is concluded that for symmetrical temperature-time profiles the extent of degradation in the real nonisothermal condition is less than that in the nominal isothermal condition. However, with the temperature fluctuaction obtainable with the current thermoregulated devices, the difference between the two is usually very small and can be neglected except for extremely fast reactions.