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Jin-ling Zhou,1,* Xiu-ying Huang,2,* Han-chen Qiu,3 Ri-zhi Gan,1 Huan Zhou,1 Hong-qing Zhu,1 Xuan-xuan Zhang,1 Guo-dong Lu,4 Gang Liang1 1School of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2Liuzhou Employment Service Centre for the Disabled, Liuzhou, People’s Republic of China; 3Department of Pharmacy, The People’s Hospital of Hezhou, Hezhou, People’s Republic of China; 4School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gang LiangDepartment of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning 530021, Guangxi Province, People’s Republic of ChinaTel + 86 771 5302271Fax + 86 771 5358272Email lianggang@gxmu.edu.cnGuo-dong LuDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Province, People’s Republic of ChinaTel + 86 771 535 8114Fax + 86 771 5350823Email golden_lu@hotmail.comIntroduction: Saponin of Schizocapsa plantaginea Hance I (SSPH I), a novel bioactive phytochemical isolated from the rhizomes of Schizocapsa plantaginea, has been demonstrated to exhibit anti-cancer activity against various tumors in preclinical studies. However, the molecular mechanisms involved in the suppression of hepatocellular carcinoma (HCC) are poorly understood. The present study aimed at analyzing the effects of SSPH I on autophagy and apoptosis in vitro.Methods: MTT and colony forming assays were used to detect cell viability and cell proliferation. Hoechst 33,258 staining and flow cytometry were used to determine apoptosis and ROS production. The apoptosis and autophagy-related protein expression levels were evaluated via Western blot assay. Characteristics of autophagy and apoptosis were observed by transmission electron microscopy. Lysosomal activity was stained with Lyso-Tracker Red and Magic Red Cathepsin B.Results: The results showed that SSPH I exhibited potent anti-cancer activity and proliferation in HepG2 and BEL-7402 cells and inhibited HepG2 cells through inhibiting autophagy and promoting apoptosis. The mechanistic study indicated that the inhibition of autophagy of SSPH I was mediated by blocking autophagosome–lysosome fusion. Additionally, we found that SSPH I could mediate the activation of MAPK/ERK1/2 signaling pathway, and the use of NAC (ROS inhibitor) and U0126 (MEK1/2 inhibitor) converted the effect of SSPH I on apoptosis and autophagy in HepG2 cells.Conclusion: These data suggest that SSPH I induces tumor cells apoptosis and reduces autophagy in vitro by inducing ROS and activating MAPK/ERK1/2 signaling pathway, indicating that SSPH I might be a novel agent for the treatment of HCC.Keywords: saponins of Schizocapsa plantaginea Hance I, SSPH I, autophagy, hepatocellular carcinoma cells, apoptosis, ROS, MAPK

Light use efficiency (LUE) defines the vegetation efficiency of converting radiative energy into biochemical energy through photosynthesis. Estimating the maximum LUE (ϵ max) is critical yet challenging for quantifying gross primary production (GPP) using LUE-based models. This study describes an analytical method for estimating ϵ max based on water use efficiency (WUE) as determined by plant water use and carbon gain. Unlike other complex parameterization schemes, this WUE-based method is simple and requires four variables relatively easy to acquire. The WUE-based ϵ max estimates compare favorably well with values based on traditional curve fitting method and that reported in the literature, and clearly distinguished ϵ max between C3 (1.48 0.33 {g C M}}{J}}{ - 1}) and C4 (2.63 0.21 {g C M}}{J}}{-1}}) dominated ecosystems. The range in ϵ max estimates was narrow across different years and sites within a biome. The WUE-based ϵ max estimate is theoretically constrained by vegetation water use and can be directly incorporated into LUE models for GPP estimation across ecosystems.

Rui-huan Gan,1,* Li-song Lin,2,* Jing Xie,3–5,* Li Huang,2,4 Lin-can Ding,2 Bo-hua Su,2 Xian-e Peng,1,5 Da-li Zheng,4,5 You-guang Lu1,3 1Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 3Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350000, People’s Republic of China; 4Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, People’s Republic of China; 5Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350122, People’s Republic of China*These authors contributed equally to this workCorrespondence: You-guang LuDepartment of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou 350000, People’s Republic of ChinaTel +86 591 8373 6429Fax +86 591 8372 0599Email fjlyg63@fjmu.edu.cnXian-e PengDepartment of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, 1 Xue Yuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaTel +86 138 0951 6580Fax +86 591 8372 0599Email fmuxe@163.comPurpose: The Notch signaling pathway plays an oncogenic role in tongue squamous cell carcinoma. The aim of this study was to inhibit the proliferation and self-renewal of tongue cancer cells by applying Notch signaling pathway inhibitor FLI-06 (Selleck, USA) and to lay a foundation for the clinically targeted treatment of tongue cancer for the future.Methods: The mRNA expression level of Notch1 and the overall survival rate of patients with tongue cancer were examined by analyzing the TCGA database. Tongue cancer cells were treated with FLI-06. Cell proliferation, apoptosis, and stem cell self-renewal ability were tested in appropriate ways. A xenograft mouse model was established to observe tumor growth.Results: From the TCGA data, we demonstrated that patients with high expression of Notch1 had a poor prognosis. We observed that the Notch signaling pathway inhibitor FLI-06 can restrain the activation of the Notch signaling pathway, decrease cell proliferation and induce cell apoptosis in vitro. The xenograft experiment indicated that intraperitoneal injection of FLI-06 inhibited tumor growth and increased cell apoptosis. FLI-06 suppressed both the mRNA and protein expression of Notch receptor and Notch targeted genes. We also observed that FLI-06 suppressed the proliferation of tongue cancer stem cells.Conclusion: FLI-06 can block the proliferation and self-renewal of tongue cancer cells. It is inferred that this compound, which inhibits the Notch signaling pathway, may serve as a potential targeted drug for the treatment of tongue cancer in the clinic.Keywords: tongue cancer, Notch signaling pathway, Notch inhibitor, cancer stem cells

© 2018 Elsevier Inc. Accurate quantification of terrestrial evapotranspiration (ET) is essential to understand the Earth's energy and water budgets under climate change. However, despite water and carbon cycle coupling, there are few diagnostic global evapotranspiration models that have complete carbon constraint on water flux run at a high spatial resolution. Here we estimate 8-day global ET and gross primary production (GPP) at 500 m resolution from July 2002 to December 2017 using a coupled diagnostic biophysical model (called PML-V2) that, built using Google Earth Engine, takes MODIS data (leaf area index, albedo, and emissivity) together with GLDAS meteorological forcing data as model inputs. PML-V2 is well calibrated against 8-day measurements at 95 widely-distributed flux towers for 10 plant functional types, indicated by Root Mean Square Error (RMSE) and Bias being 0.69 mm d −1 and −1.8% for ET respectively, and being 1.99 g C m −2 d −1 and 4.2% for GPP. Compared to that performance, the cross-validation results are slightly degraded, with RMSE and Bias being 0.73 mm d −1 and −3% for ET, and 2.13 g C m −2 d −1 and 3.3% for GPP, which indicates robust model performance. The PML-V2 products are noticeably better than most GPP and ET products that have a similar spatial resolution, and suitable for assessing the influence of carbon-induced impacts on ET. Our estimates show that global ET and GPP both significantly (p < 0.05) increased over the past 15 years. Our results demonstrate it is very promising to use the coupled PML-V2 model to improve estimates of GPP, ET and water use efficiency, and its uncertainty can be further reduced by improving model inputs, model structure and parameterisation schemes.

Copyright © 2018 John Wiley & Sons, Ltd. Accurate quantification of terrestrial evapotranspiration and ecosystem productivity is of significant merit to better understand and predict the response of ecosystem energy, water, and carbon budgets under climate change. Existing diagnostic models have different focus on either water or carbon flux estimates with various model complexity and uncertainties induced by distinct representation of the coupling between water and carbon processes. Here, we propose a diagnostic model to estimate evapotranspiration and gross primary production that is based on biophysical mechanism yet simple for practical use. This is done by coupling the carbon and water fluxes via canopy conductance used in the Penman–Monteith–Leuning equation (named as PML_V2 model). The PML_V2 model takes Moderate Resolution Imaging Spectrometer leaf area index and meteorological variables as inputs. The model was tested against evapotranspiration and gross primary production observations at 9 eddy-covariance sites in Australia, which are spread across wide climate conditions and ecosystems. Results indicate that the simulated evapotranspiration and gross primary production by the PML_V2 model are in good agreement with the measurements at 8-day timescale, indicated by the cross site Nash–Sutcliffe efficiency being 0.70 and 0.66, R2 being 0.80 and 0.75, and root mean square error being 0.96 mm d−1 and 1.14 μmol m−2 s−1 for evapotranspiration and gross primary production, respectively. As the PML_V2 model only requires readily available climate and Moderate Resolution Imaging Spectrometer vegetation dynamics data and has few parameters, it can potentially be applied to estimate evapotranspiration and carbon assimilation simultaneously at long-term and large spatial scales.

© 2017 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd Objectives: Audiometric tests provide information about hearing in otitis media with effusion (OME). Questionnaires can supplement this information by supporting clinical history-taking as well as potentially providing a standardized and comprehensive assessment of the impact of the disease on a child. There are many possible candidate questionnaires. This study aimed to assess the quality and usability of parent / child questionnaires in OME assessment. Design and main outcome measures: Fifteen, published questionnaires, commonly used in audiological departments (Auditory Behaviour in Everyday Life (ABEL), Children's Auditory Performance Scale (CHAPS), Children's Home Inventory for Listening Difficulties (CHILD), Children's Outcome Worksheets (COW), Evaluation of Children's Listening and Processing Skills (ECLiPS), Early Listening Function (ELF), Fisher's Auditory Problem Checklist (FAPC), Hearing Loss 7 (HL-7), Listening Inventory for Education- Revised (LIFE-R Student), Listening Inventory for Education UK Individual Hearing Profile (LIFE-UK IHP), LittlEARS Auditory Questionnaire (LittlEARS), Listening Situations Questionnaire (LSQ), Otitis Media 6 (OM-6), Quality of Life in Children's Ear Problems (OMQ-14), Parents’ Evaluation of Aural/Oral Performance of Children (PEACH) were assessed according to the following 8 criteria: conceptual clarity, respondent burden, reliability, validity, normative data, item bias, ceiling/ floor effects, and administrative burden. Results: ECLiPS, LittlEARS and PEACH scored highest overall based on the assessment criteria established for this study. None of the questionnaires fully satisfied all 8 criteria. Although all questionnaires assessed issues considered to be of at least adequate relevance to OME, the majority had weaknesses with respect to the assessment of psychometric properties, such as item bias, floor/ceiling effects or measurement reliability and validity. Publications reporting on the evaluation of reliability, validity, normative data, item bias and ceiling/floor effects were not available for most of the questionnaires. Conclusions: This formal evaluation of questionnaires, currently available to clinicians, highlights three questionnaires as potentially offering a useful adjunct in the assessment of OME in clinical or research settings. These were the ECLiPS, which is suitable for children aged 6 years and older, and either the LittlEARS or the PEACH for younger children. The latter two are narrowly focused on hearing, whereas ECLiPS has a broader focus on listening, language and social difficulties.

The article devoted to the possible mechanisms of the impact of stress (that related to the military conflict in eastern Ukraine) for the indicators of physical and mental health in children, those were an internally displaced persons or those who lost their parents. This indicates are the need for a comprehensive integrated approach to health disorders and the search for ways to save it and provide the rehabilitation., Рассмотрены возможные механизмы влияния стресса, связанного с военным конфликтом на Востоке Украины, на показатели физического и психического здоровья детей пострадавших категорий — внутренне перемещенных лиц и таких, которые потеряли отца. Показана необходимость комплексного интегративного подхода к нарушения здоровья и поиска путей его сохранения и восстановления., Розглянуто можливі механізми впливу стресу, пов'язаного з воєнним конфліктом на Сході України, на показники фізичного та психічного здоров'я дітей постраждалих категорій — внутрішньо переміщених осіб і таких, що втратили батьків. Показано необхідність комплексного інтегративного підходу до порушень здоров'я та пошуку шляхів його збереження та відновлення.

In the article the features of the etiology, pathogenesis and clinical manifestations of acute respiratory infections (ARI) in children are presented. The authors have substantiated indications for symptomatic treatment, taking into account the basic pathogenesis of ARI. The questions of the possibility of use of complex preparations for the treatment of acute respiratory infections in children, which are allowed providing multisimptomatic effects such as analgesic, antipyretic, anti-inflammatory, antiallergic and antitussive are underlined. One of such preparation is «Milistan multisimptomatic». The use of complex preparation «Milistan multisimptomatic» allows to effect on all the main links of the ARI pathogenesis, quickly and effectively removes the clinical symptoms and improves quality of life for patients.Key words: acute respiratory infections, symptomatic treatment, combined preparations, children., В статье представлены особенности этиологии, патогенеза и клинических проявлений острых респираторных инфекций (ОРИ) у детей. Авторами обоснованы показания к назначению симптоматического лечения с учетом основных звеньев патогенеза ОРИ. Освещены вопросы возможности применения для лечения ОРИ у детей комплексных препаратов, позволяющих оказывать мультисимптомное воздействие — анальгетическое, жаропонижающее, противовоспалительное, противоаллергическое и противокашлевое, одним из которых является «Милистан мультисимптомный». Применение комплексного препарата «Милистан мультисимптомный» позволяет воздействовать на все основные звенья патогенеза ОРИ, быстро и эффективно устранять её клинические симптомы и улучшать качество жизни пациентов.Ключевые слова: острые респираторные инфекции, симптоматическое лечение, комбинированные препараты, дети., У статті наведені особливості етіології, патогенезу та клінічних проявів гострих респіраторних інфекцій (ГРІ) у дітей. Авторами обґрунтовані показання до призначення симптоматичного лікування з урахуванням основних ланок патогенезу ГРІ. Висвітлено питання можливості застосування для лікування ГРІ у дітей комплексних препаратів, що дозволяють чинити мультисимптомну дію — анальгетичну, жарознижувальну, протизапальну, протиалергічну і протикашльову, одним з яких є «Мілістан мультисимптомний». Застосування комплексного препарату «Мілістан мультисимптомний» дозволяє впливати на всі основні ланки патогенезу ГРІ, швидко та ефективно усувати її клінічні симптоми та покращувати якість життя пацієнтів.Ключові слова: гострі респіраторні інфекції, симптоматичне лікування, комбіновані препарати, діти.