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Contrast-enhanced computed tomography scans (CECT) are routinely used in the evaluation of different clinical scenarios, including the detection and characterization of hepatocellular carcinoma (HCC). Quantitative medical image analysis has been an exponentially growing scientific field. A number of studies reported on the effects of variations in the contrast enhancement phase on the reproducibility of quantitative imaging features extracted from CT scans. The identification and labeling of phase enhancement is a time-consuming task, with a current need for an accurate automated labeling algorithm to identify the enhancement phase of CT scans. In this study, we investigated the ability of machine learning algorithms to label the phases in a dataset of 59 HCC patients scanned with a dynamic contrast-enhanced CT protocol. The ground truth labels were provided by expert radiologists. Regions of interest were defined within the aorta, the portal vein, and the liver. Mean density values were extracted from those regions of interest and used for machine learning modeling. Models were evaluated using accuracy, the area under the curve (AUC), and Matthew's correlation coefficient (MCC). We tested the algorithms on an external dataset (76 patients). Our results indicate that several supervised learning algorithms (logistic regression, random forest, etc.) performed similarly, and our developed algorithms can accurately classify the phase of contrast enhancement.

Previous studies have shown that deep models are often over-parameterized, and this parameter redundancy makes deep compression possible. The redundancy of model weight is often manifested as low rank and sparsity. Ignoring any part of the two or the different distributions of these two characteristics in the model will lead to low accuracy and a low compression rate of deep compression. To make full use of the difference between low-rank and sparsity, a unified framework combining low-rank tensor decomposition and structured pruning is proposed: a hybrid model compression method based on sensitivity grouping (HMC). This framework unifies the existing additive hybrid compression method (AHC) and the non-additive hybrid compression method (NaHC) proposed by us into one model. The latter group the network according to the sensitivity difference of the convolutional layer to different compression methods, which can better integrate the low rank and sparsity of the model compared with the former. Experiments show that our approach achieves a better trade-off between test accuracy and compression ratio when compressing the ResNet family of models than other recent compression methods using a single strategy or additive hybrid compression.

Background The association between out-of-hospital cardiac arrest patient survival and advanced life support response time remained controversial. We aimed to test the hypothesis that for adult, non-traumatic, out-of-hospital cardiac arrest patients, a shorter advanced life support response time is associated with a better chance of survival. We analyzed Utstein-based registry data on adult, non-traumatic, out-of-hospital cardiac arrest patients in Taipei from 2011 to 2015. Methods Patients without complete data, witnessed by emergency medical technicians, or with response times of ≥ 15 minutes, were excluded. We used logistic regression with an exposure of advanced life support response time. Primary and secondary outcomes were survival to hospital discharge and favorable neurological outcomes (cerebral performance category ≤ 2), respectively. Subgroup analyses were based on presenting rhythms of out-of-hospital cardiac arrest, bystander cardiopulmonary resuscitation, and witness status. Results A total of 4,278 cases were included in the final analysis. The median advanced life support response time was 9 minutes. For every minute delayed in advanced life support response time, the chance of survival to hospital discharge would reduce by 7% and chance of favorable neurological outcome by 9%. Subgroup analysis showed that a longer advanced life support response time was negatively associated with the chance of survival to hospital discharge among out-of-hospital cardiac arrest patients with shockable rhythm and pulse electrical activity groups. Conclusions In non-traumatic, adult, out-of-hospital cardiac arrest patients in Taipei, a longer advanced life support response time was associated with declining odds of survival to hospital discharge and favorable neurologic outcomes, especially in patients presenting with shockable rhythm and pulse electrical activity.

This study investigated the impact of retinal fluid tolerance on retinal thickness and visual acuity in patients with neovascular age-related macular degeneration after 18 months of treatment using intravitreal aflibercept. This retrospective study was based on the medical records of 90 eyes presenting persistent or recurrent retinal fluid retention after 3 months of aflibercept loading injections. We defined the fluid tolerance ratio as the sum of fluid-tolerance duration divided by the total duration of retinal fluid observed throughout the follow-up period. Eyes were categorized into strict, intermediate, and relaxed group based on their fluid tolerance ratio (= 0, = 30%, respectively). The mean total follow-up time was 556 days. The relaxed group required fewer injections than the strict group (4.92 vs 7.50 injections, P < 0.01) and presented a similar reduction in retinal thickness (-57.50 vs -71.65 μm, P = 0.83). Nonetheless, the two groups were similar in terms of final visual acuity (logarithm of the minimum angle of resolution 0.72 vs 0.70, P = 0.95) and visual gains (4.21 vs -1.12 letters, P = 0.56). These results indicate that in the setting of limited medical resources, a fluid-tolerant approach provides comparable gains in visual acuity. Reducing the number of injections may also improve adherence to therapy.

Distracted driving behavior is one of the main factors of road accidents. Accurately predicting the risk of driving behavior is of great significance to the active safety of road transportation. The large amount of information collected by the sensors installed on the vehicle can be identified by the algorithm to obtain the distracted driving behavior data, which can be used to predict the driving behavior risk of the vehicle and the area. In this paper, a new neural network named Driving Behavior Risk Prediction Neural Network (DBRPNN) is developed for prediction based on the distracted driving behavior data. The network consists of three modules: the Feature Processing Module, the Memory Module, and the Prediction Module. In this process, attribute data (time in a day, daily driving time, and daily driving mileage) that can reflect external factors and driver statuses, are added to the network to increase the accuracy of the model. We predicted the driving behavior risk of different objects (Vehicle and Area). For the applicability improvement of the model, we further classify the distracted driving behavior categories, and DBRPNN can provide more accurate risk prediction. The results show that compared with traditional models (Classification and Regression Tree, Support Vector Machines, Recurrent Neural Network, and Long Short-Term Memory), DBRPNN has better prediction performance. The method proposed in this paper has been fully verified and may be transplanted into active safety early warning system for more accurate and flexible application.

Isodon rubescens (Hemsley) H. Hara (Lamiaceae) is a traditional Chinese medicine plant that has been used to treat various human diseases and conditions such as inflammation, respiratory and gastrointestinal bacterial infections, and malignant tumors. However, the contents of the main active components of I. rubescens from different origins differ significantly, which greatly affected its quality. Therefore, a molecular method to identify and classify I. rubescens is needed. Here, we report the DNA sequence of the chloroplast genome of I. rubescens collected from Lushan, Henan province. The genome is 152,642 bp in length and has a conserved structure that includes a pair of IR regions (25,726 bp), a LSC region (83,527 bp) and a SSC region (17,663 bp). The chloroplast genome contains 113 unique genes, four rRNA genes, 30 tRNA genes, and 79 protein-coding genes, 23 of which contain introns. The protein-coding genes account for a total of 24,412 codons, and most of them are A/T biased usage. We identified 32 simple sequence repeats (SSRs) and 48 long repeats. Furthermore, we developed valuable chloroplast molecular resources by comparing chloroplast genomes from three Isodon species, and both mVISTA and DnaSP analyses showed that rps16-trnQ, trnS-trnG, and ndhC-trnM are candidate regions that will allow the identification of intraspecific differences within I. rubescens. Also 14 candidate fragments can be used to identify interspecific differences between species in Isodon. A phylogenetic analysis of the complete chloroplast genomes of 24 species in subfamily Nepetoideae was performed using the maximum likelihood method, and shows that I. rubescens clustered closer to I. serra than I. lophanthoides. Interestingly, our analysis showed that I. rubescens (MW018469.1) from Xianyang, Shaanxi Province (IR-X), is closer to I. serra than to the other two I. rubescens accessions. These results strongly indicate that intraspecific diversity is present in I. rubescens. Therefore, our results provide further insight into the phylogenetic relationships and interspecific diversity of species in the genus Isodon.

It is already known that the process of photosynthesis depends on the quality and intensity of light. However, the influence of the new light sources recently used in horticulture, known as Light Emitting Diodes (LEDs), on this process is not yet fully understood. Chlorophyll a fluorescence measurement has been widely used as a rapid, reliable, and noninvasive tool to study the efficiency of the photosystem II (PSII) and to evaluate plant responses to various environmental factors, including light intensity and quality. In this work, we tested the responses of the tomato photosynthetic apparatus to different light spectral qualities. Our results showed that the best performance of the photosynthetic apparatus was observed under a mixture of red and blue light (R7:B3) or a mixture of red, green and blue light (R3:G2:B5). This was demonstrated by the increase in the effective photochemical quantum yield of PSII (Y[II]), photochemical quenching (qP) and electron transport rate (ETR). On the other hand, the mixture of red and blue light with a high proportion of blue light led to an increase in non-photochemical quenching (NPQ). Our results can be used to improve the production of tomato plants under artificial light conditions. However, since we found that the responses of the photosynthetic apparatus of tomato plants to a particular light regime were cultivar-dependent and there was a weak correlation between the growth and photosynthetic parameters tested in this work, special attention should be paid in future research.

Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH.

Due to high humidity, the ageing of room temperature vulcanized silicone rubber (RTV) has been a serious problem in Southwestern China. In order to solve the problem of RTV life prediction, the aging classification method was established by analyzing the microtopography of RTV samples in this paper. Besides, the comprehensive analysis of RTV element content, partial element content ratio, and major chemical groups of RTV samples in each aging level were conducted. It is found that as the ageing level increases, the element contents of C, Si, O, Al change accordingly and the ratio of C:Si drops from 2.39 to 1.54, and absorption peaks of the chemical groups of Si-(CH3)2, Si-O-Si, Si-CH3 and C-H in CH3 decrease. This work can enrich the investigation of RTV, and may provide useful reference for performance evaluation and replacement of RTV in substations.

Study objectiveThe purpose of this feasibility study is to develop and validate a new assessment tool and scoring system for multitasking competency for physicians in-training in a timed simulated setting. The multitasking competency includes ability to appropriately prioritize and implement tasks for different patients who present simultaneously.MethodsWe designed three single task stations with different levels of difficulty and priority. These skill stations were then combined to create a multitasking simulation scenario. Skill checklists and the global rating scale were utilized to assess the participants' performance. A multitasking score, multitasking index, and priority score were developed to measure the multitasking ability of participants.ResultsThirty-three first-year postgraduate physicians were recruited for this prospective study. The total performance scores were significantly higher for the single-tasking stations than for the multitasking scenario. In terms of the time needed to complete the tasks, the participants spent more time on the multitasking scenario than on the single-tasking scenario. There were significant correlations between the global rating scale and the multitasking score (rho = 0.693, p < 0.001) and between the global rating scale and the multitasking index (rho = 0.515, p < 0.001). The multitasking score, multitasking index, and priority score did not have any significant correlations with the total single-tasking score.ConclusionWe demonstrated that the use of a simulated multitasking scenario could be an effective method of assessing multitasking ability and allow assessors to offer better quality feedback.

PURPOSE:To evaluate the clinical characteristics and evolution of lamellar macular hole (LMH) in high myopia and the parameters associated with structural worsening, defined as the development of foveal detachment or full-thickness macular hole. METHODS:Patients with high myopia and LMH were retrospectively recruited. The clinical characteristics and various parameters of optical coherence tomography were identified at baseline and during follow-up visits. Cox regression analysis was used to evaluate the hazard ratios for foveal detachment and full-thickness macular hole. RESULTS:Among 112 eyes (98 patients), 64.3% were female; the mean axial length of all eyes was 29.6 ± 1.9 mm. The 'LMH without retinoschisis' group accounted for 39.3% of the eyes. Forty-two percent developed structural worsening within a median follow-up of 67 months. Multivariable regression on all cases showed elevated tissue inside the LMH (P = 0.003) protected against structural worsening while V-shaped LMH (P = 0.006) predicted it. In the "LMH with retinoschisis group", ellipsoid zone disruption (P = 0.035), and V-shaped LMH (P = 0.014) predicted structural worsening, while elevated tissue inside the LMH (P = 0.028) protected against it. In the "LMH without retinoschisis group", no associated factor was identified. CONCLUSIONS:LMHs in high myopia are unstable, especially those with V-shaped LMH. Elevated tissue inside LMHs have a protective effect against further structural worsening.

Regional differences and regulatory mechanisms of vegetation productivity response to changing environmental conditions constitute a core issue in macroecological researches. To verify the main limiting factors of different macrosystems [temperature-limited Tibetan Plateau (TP), precipitation-limited Mongolian Plateau (MP), and nutrient-limited Loess Plateau (LP)], we conducted a comparative survey of the east-west grassland transects on the three plateaus and explored the factors limiting regional productivity and their underlying mechanisms. The results showed that aboveground net primary productivity (ANPP) of LP (109.10 ± 16.76 g m-2 yr-1) was significantly higher than that of MP (66.71 ± 11.11 g m-2 yr-1) and TP (57.02 ± 10.59 g m-2 yr-1). The response rate of ANPP with environmental changes was different among different plateaus, being closely related to the main limiting factors. On MP, this was precipitation, on LP it was temperature and nutrients, and on TP, it was non-specific, reflecting restriction by the extremely low temperature. After autocorrelation screening of environmental factors, different regions exhibited different productivity response mechanisms. MP was mainly influenced by temperature and precipitation, LP was influenced by temperature and nutrient, and TP was influenced by nutrient, reflecting the modifying effect of the main limiting factors. The effect of each regional environment on ANPP was 72.56% on average and only 27.18% after simple regional integration. The regional model could optimize the simulation error of the integrated model, and the relative deviations in MP, LP, and TP were reduced by 31.76%, 17.22%, and 2.23%, respectively. These findings indicate that the grasslands on the three plateaus may have different or even the opposite mechanisms to control productivity.

Native intact N-glycopeptide analysis can provide access to the comprehensive characteristics of N-glycan occupancy, including N-glycosites, N-glycan compositions, and N-glycoproteins for complex samples. The sample pre-processing method used for the analysis of intact N-glycopeptides usually depends on the enrichment of low abundance N-glycopeptides from a tryptic peptide mixture using hydrophilic substances before LC-MS/MS detection. However, the number of identified intact N-glycopeptides remains inadequate to achieve an in-depth profile of the N-glycosylation landscape. Here, we optimized the sample preparation workflow prior to LC-MS/MS analysis by systematically comparing different analytical methods, including the use of different sources of trypsin, combinations of different proteases, and different enrichment materials. Finally, we found that the combination of Trypsin (B)/Lys-C digestion and zwitterionic HILIC (Zic-HILIC) enrichment significantly improved the mass spectrometric characterization of intact N-glycopeptides, increasing the number of identified intact N-glycopeptides and offering better analytical reproducibility. Furthermore, the optimized workflow was applied to the analysis of intact N-glycopeptides in two-dimensional (2D) and three-dimensional (3D)-cultured breast cancer cells in vitro and xenografted tumors in mice. These results indicated that the same breast cancer cells, when cultured in different microenvironments, can show different N-glycosylation patterns. This study also provides an interesting comparison of the N-glycoproteome of breast cancer cells cultured in different growth conditions, indicating the important role of N-glycosylated proteins in cancer cell growth and the choice of the cell culture model for studies in tumor biology and drug evaluation.

Accurate Origin-Destination (OD) prediction is significant for effective traffic monitor, which can support operation decision in traffic planning and management field. The enclosed expressway network system like toll gates system in China can collect mounts of trip records which can be gathered for OD prediction. The paper develops a novel neural network, which is named Expressway OD Prediction Neural Network (EODPNN) for toll data-based prediction. The network consists of the following three modules: The Feature Extension Module, the Memory Module, and the Prediction Module. In the process, the attributes data which can reflect the city attribute such as GDP, population, and the number of vehicles are considered to embeded into the notwork to increase the accuracy of the model. For the applicability improvment of the model, we categorize the cities in multiple classes based on their economy and population scales in this paper, which can provide a higher accurate prediction of OD by EODPNN. The results shows that, comparing to the traditional model like ARIMA and SVM, or typical neural networks like Bidirectional Long Short-term Memory, the EODPNN delivers a better prediction performance. The method proposed in this paper has been fully verified and has a potential to transplant to the other OD data-based management systems for a more accurate and flexible prediction.

MicroRNAs (miRNAs) are small noncoding RNAs that critically regulate gene expression. Their abundance and function have been linked to a range of physiologic and pathologic processes. In aged monkey muscle, miR-451a and miR-144-3p were far more abundant than in young monkey muscle. This observation led us to hypothesize that miR-451a and miR-144-3p may influence muscle homeostasis. To test if these conserved microRNAs were implicated in myogenesis, we investigated their function in the mouse myoblast line C2C12. The levels of both microRNAs declined with myogenesis; however, only overexpression of miR-451a, but not miR-144-3p, robustly impeded C2C12 differentiation, suggesting an inhibitory role for miR-451a in myogenesis. Further investigation of the regulatory influence of miR-451a identified as one of the major targets Sparc mRNA, which encodes a secreted protein acidic and rich in cysteine (SPARC) that functions in wound healing and cellular differentiation. In mouse myoblasts, miR-451a suppressed Sparc mRNA translation. Together, our findings indicate that miR-451a is downregulated in differentiated myoblasts and suggest that it decreases C2C12 differentiation at least in part by suppressing SPARC biosynthesis.

Hypertriglyceridaemia is one of the most common causes of severe acute pancreatitis (SAP). However, the association between elevated triglycerides (TG) level in hospital stay and outcome in SAP patients with normal TG level at admission has not been clearly demonstrated. This retrospective study assessed the serum TG levels of patients with SAP admitted to the intensive care unit (ICU) in 2017. Variables with a statistically significant association with the incidence of in-hospital TG elevation, as determined by univariate analysis, were analysed using a logistic regression model to predictors. Of the 99 patients included in the study, TG levels were within the normal range in 59 (59.59%) patients at admission. Among patients with normal TG level when admitted to ICU, 28 (47.46%) experienced at least one episode of TG level elevation during their ICU stay. Elevated TG level in hospitalization is associated with an increased length of ICU stay, as well as increased mortality. In addition to other factors, propofol usage was independently associated with the occurrence of in-hospital-TG elevation. To conclude, we retrospectively investigated the incidence, outcome, and risk factors for in-hospital TG elevation events in SAP patients admitted to the ICU. We found a high incidence of both preexisting and in-hospital-acquired TG elevation in SAP patients admitted to the ICU. The TG elevation that occurred during the ICU stay was associated with worse outcomes and long-term hospitalization of the ICU. Propofol usage was independently associated with the TG elevation occurrence in the ICU.

Previous studies showed that emotional faces break through interocular suppression more easily compared to neutral faces under the continuous flash suppression (CFS) paradigm. However, there is controversy over whether emotional content or low-level properties contributed to the results. In this study, we directly manipulated the meaningfulness of facial expression to test the role of emotional content in breaking CFS (b-CFS). In addition, an explicit emotion judgment for different facial expressions (happy, neutral, and fearful) used in the b-CFS task was also conducted afterwards to examine the relationship between b-CFS time and emotion judgment. In Experiment 1, face orientation and luminance polarity were manipulated to generate upright-positive and inverted-negative faces. In Experiment 2, Asian and Caucasian faces were presented to Taiwanese participants so that these stimuli served as own-race and other-race faces, respectively. We found robust face familiarity effects in both experiments within the same experimental framework: upright-positive and own-race faces had shorter b-CFS times than inverted-negative and other-race faces, respectively. This indicates potential involvement of high-level processing under interocular suppression. In Experiment 1, different b-CFS times were found between emotional and neutral faces in both upright-positive and inverted-negative conditions. Furthermore, with sufficient duration (1000 ms) participants could still extract emotional content in explicit valence judgment even from inverted-negative faces, though with a smaller degree than upright-positive faces. In Experiment 2, differential b-CFS times were found between emotional and neutral faces with own-race but not other-race faces. Correlation analyses from both experiments showed that the magnitude of emotion judgment was correlated with b-CFS time only for familiar (upright-positive / own-race) but not unfamiliar (inverted-negative / other-race) faces. These results suggest that emotional content can be extracted under interocular suppression with familiar faces, and low-level properties in unfamiliar faces may play a major role in the b-CFS time.

BACKGROUND:The escalating problem of multiple chronic conditions among older adults in China draws public health attention due to increasing proportion of the elderly population. This study sought to assess the prevalence of and factors associated with four chronic diseases in older adults in Haikou, the capital city of Hainan Province, China. METHOD:In this cross-sectional study, 9432 community-dwelling elderly people aged 60 years and older living in rural or urban areas in Haikou were investigated. The interviews collected self-reported information on the presence of four major chronic diseases, as well as socio-demographic characteristics, lifestyle factors and self-reported height and weight. FINDINGS:Overall, 31.7% (2961/9344) reported at least one of the four chronic diseases. The prevalence of hypertension, diabetes mellitus, COPD, and stroke was 26.0% (2449/9407), 8.0% (749/9371), 1.0% (95/9360), and 1.9% (175/9382), respectively. Common correlates of the four major chronic diseases were older age, being engaged in intellectual work, currently being a smoker and obesity. Gender, locality of residence, and alcohol consumptions were also found to be associated to some of the chronic conditions. CONCLUSION:This finding indicates that multiple chronic conditions among elderly people in Haikou are prevalent and warrant special attention to reduce diseases burden and align health care services to cater the holistic elderly patients' need.

This study explored whether cataract surgery precipitates diabetic retinopathy (DR) development in diabetic patients without previous DR. Patients with the diagnosis of type II diabetes but without DR were selected from the Longitudinal Health Insurance Database 2000. Patients who received cataract surgery between January 1, 2000, and December 31, 2010, were included in the case group, and the control group was matched to the case group by age, sex, and index year. The postoperative incidence rates of nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) were the main outcomes studied and were adjusted by age, sex, comorbidities, and statin, fibrate, angiotensin-converting-enzyme inhibitor (ACEI), oral hypoglycemic agents (OHA), and insulin use. In our cohort, patients who had dyslipidemia and used statins were more likely to undergo cataract surgery. Among diabetic patients without previous DR, patients receiving cataract surgery had a higher risk of NDPR development (adjusted hazard ratio = 1.48, 95% confidence interval = 1.15-1.91). No statistical difference was observed in PDR or DME development between operative and nonoperative groups. In additional stratified analyses, female sex, older age, comorbidities, surgery within 5 years, statin, ACEI, OHA, and insulin use increased the risk of NPDR development. In an adjusted Cox regression model, cataract surgery, OHA and insulin use were found to be risk factors for NPDR development. Cataract surgery with complications increased post-operative risks for NPDR were even higher, and the significant influence from cataract surgery persisted 5 years after surgery.

Process-based models can be usefully employed for the assessment of field and regional-scale impact of drought on crop yields. However, in many instances, especially when they are used at the regional scale, it is necessary to identify the parameters and input variables that most influence the outputs and to assess how their influence varies when climatic and environmental conditions change. In this work, two different crop models, able to represent yield response to water, Aquacrop and SAFYE, were compared, with the aim to quantify their complexity and plasticity through Global Sensitivity Analysis (GSA), using Morris and EFAST (Extended Fourier Amplitude Sensitivity Test) techniques, for moderate to strong water limited climate scenarios. Although the rankings of the sensitivity indices was influenced by the scenarios used, the correlation among the rankings, higher for SAFYE than for Aquacrop, assessed by the top-down correlation coefficient (TDCC), revealed clear patterns. Parameters and input variables related to phenology and to water stress physiological processes were found to be the most influential for Aquacrop. For SAFYE, it was found that the water stress could be inferred indirectly from the processes regulating leaf growth, described in the original SAFY model. SAFYE has a lower complexity and plasticity than Aquacrop, making it more suitable to less data demanding regional scale applications, in case the only objective is the assessment of crop yield and no detailed information is sought on the mechanisms of the stress factors affecting its limitations.

Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS.A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83).Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.

Optic neuritis is highly correlated with multiple sclerosis and is a major cause of acute visual loss and long-term neuronal degeneration. Primary cerebral hypoperfusion has been reported in brain demyelinating diseases. This study investigated whether peripapillary perfusion is changed in patients with acute optic neuritis (AON).This three-year cohort study was conducted from September 1 2012, to August 31, 2015. Two hundred and forty-one patients with non-glaucomatous acute optic neuropathy were screened, and 42 non-highly myopic patients who had suffered their first episode of unilaterally idiopathic AON were studied. All cases received spectral-domain optical coherence tomography (OCT) examination, general survey, and standard corticosteroid therapy. OCT images were analyzed using a customized MATLAB program for measuring peripapillary choroidal thickness (PCT). Multivariate regression models were constructed to identify factors that are significantly related to peripapillary perfusion.Decreased PCT was found in eyes experiencing AON combined with disc swelling (the ratio of lesion eye PCT/fellow eye PCT was 0.87 ± 0.08; range, from 0.75 to 1.00). In comparison to the healthy fellow eyes, approximately every 26% increase in the thickness of the retinal nerve fiber layer due to axonal swelling was associated with a 10% decreased thickness of PCT. Thinner PCT is also correlated with poorer trough vision, which may lead to poorer final vision. These findings were obvious in patients with optic papillitis but not in patients with retrobulbar neuritis.Peripapillary vascular hypoperfusion was found in patients experiencing AON combined with disc swelling. These findings are unlike those for other ocular inflammatory diseases but are consistent with cerebral hypoperfusion, which is found in brain demyelinating diseases; thus, these findings may represent a new neurovascular model in this field.

Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

The purpose of current study aims to investigate the development and progression of diabetic retinopathy (DR) in patients with diabetic nephropathy (DN) in a nationwide population-based cohort in Taiwan. Newly diagnosed DN patients and age- and sex-matched controls were identified from the Taiwanese Longitudinal Health Insurance Database from 2000 to 2010. We studied the effects of age, sex, hypertension, dyslipidemia, diabetic polyneuropathy (DPN), and medications on the development of nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME) in patients with DN. Cox proportional hazard regression analyses were used to estimate the adjusted hazard ratios (HRs) of the development of DR. Our results show that the adjusted HRs of NPDR and PDR were 5.01 (95% confidence interval (CI) = 4.68-5.37) and 9.7 (95% CI = 8.15-11.5), respectively, in patients with DN as compared with patients in the non-DN cohort. At 5-year follow-up, patients with DN showed an increased HR of NPDR progression to PDR (HR = 2.26, 95% CI = 1.68-3.03), and the major comorbidities were hypertension (HR = 1.23, 95% CI = 1.10-1.38 with NPDR; HR = 1.33, 95% CI = 1.02-1.72 with PDR) and DPN (HR = 2.03, 95% CI = 1.72-2.41 in NPDR; HR = 2.95, 95% CI = 2.16-4.03 in PDR). Dyslipidemia increased the HR of developing NPDR but not PDR or DME. Moreover, DN did not significantly affect DME development (HR = 1.47, 95% CI = 0.87-2.48) or progression (HR = 0.37, 95% CI = 0.11-1.20). We concluded that DN was an independent risk factor for DR development and progression; however, DN did not markedly affect DME development in this study, and the potential association between these disorders requires further investigation.

PURPOSE:We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. METHODS AND RESULTS:Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB). CONCLUSION:The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity.

Humans have had a significant impact on the terrestrial pedosphere through activities such as agriculture and urbanization. The effects of human activities on land use and the related environmental changes were investigated through point and areal studies surrounding Meiliang Bay, which is an open area of extreme eutrophication in Taihu Lake, China. This study used remote sensing and environmental-tracer profiles [total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), grain size, and geochemical parameters] to determine the causes of changes in land use and the associated environmental parameters. The results of LUCCs (Land use/cover changes) indicate that over the past three decades, total farmland decreased by 862.49 km2, with an annual decrement rate of 28.75 km2/year, and total urbanized land increased by 859.71 km2, with an annual growth rate of 28.66 km2/year. The geochemical results indicate that the trophic state of Taihu Lake was persistently intensifying and that the TN, TP, and TOC concentrations increased twofold, threefold, and twofold, respectively, from 1949 to 2010. The sources of TN, TP, and TOC were highly similar after 1975. However, before 1974, TN and TP originated from different sources than TOC. The grassland and woodland around the lake retain nutrients and sand from the land of study area. The increase in urbanized land and tertiary industries significantly increased the sediment concentrations of TN, TP, and TOC after 1980.

Gramicidin A is an antimicrobial peptide that destroys gram-positive bacteria. The bactericidal mechanism of antimicrobial peptides has been linked to membrane permeation and metabolism disruption as well as interruption of DNA and protein functions. However, the exact bacterial killing mechanism of gramicidin A is not clearly understood. In the present study, we examined the antimicrobial activity of gramicidin A on Staphylococcus aureus using biochemical and biophysical methods, including hydroxyl radical and NAD+/NADH cycling assays, atomic force microscopy, and Fourier transform infrared spectroscopy. Gramicidin A induced membrane permeabilization and changed the composition of the membrane. The morphology of Staphylococcus aureus during gramicidin A destruction was divided into four stages: pore formation, water permeability, bacterial flattening, and lysis. Changes in membrane composition included the destruction of membrane lipids, proteins, and carbohydrates. Most interestingly, we demonstrated that gramicidin A not only caused membrane permeabilization but also induced the formation of hydroxyl radicals, which are a possible end product of the transient depletion of NADH from the tricarboxylic acid cycle. The latter may be the main cause of complete Staphylococcus aureus killing. This new finding may provide insight into the underlying bactericidal mechanism of gA.

BackgroundIt has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits.MethodThe authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents.ResultsCompared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40).ConclusionsPhysiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia.

BackgroundThe cytochrome P450 (CYP450) 2C19 681 genotypes affect the antiplatelet activity of clopidogrel. We investigated the correlation of CYP 2C19 681G > A mutation with clopidogrel resistance (CR). Additionally, we studied the effect of CR on clinical prognosis of patients with acute coronary syndrome (ACS).MethodsOne hundred ten ACS patients undergoing percutaneous coronary intervention, who were followed-up for 1 year, were included in the study. The patients were co-administered aspirin 100 mg/d and clopidogrel 75mg/d following a loading dose of 300 mg. CR was assessed on the basis of polymorphism observed in the CYP2C19 subgroup.ResultsPatients in GG genotype group exhibited greater inhibition of platelet aggregation than patients in GA and AA genotype groups (16.2 ± 10.1%; 10.2 ± 9.9%; 8.0 ± 5.9%, respectively, p < 0.01). CYP2C19 681GG genotype group was associated with lower CR than CYP2C19 681A allele (GA + AA) group (9/59 vs. (12+5)/51; p = 0.009). Over a follow-up of 12 months, the incidence of recurrent angina, acute myocardial infarction, and intra-stent thrombosis in CYP2C19 681 GG carriers was significantly lower than that in CYP2C19 681A allele (GA + AA) group (2/59 vs. 8/51, 1/59 vs. 6/51, 0 vs. 4/51, respectively, p < 0.05).ConclusionCYP 2C19*2 is associated with reduced clopidogrel antiplatelet activity and might be an important marker for poor prognosis of ACS.

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

Climate and human-driven changes play an important role in regional droughts. Northwest Yunnan Province is a key region for biodiversity conservation in China, and it has experienced severe droughts since the beginning of this century; however, the extent of the contributions from climate and human-driven changes remains unclear. We calculated the ecosystem evapotranspiration (ET) and water yield (WY) of northwest Yunnan Province, China from 2001 to 2013 using meteorological and remote sensing observation data and a Surface Energy Balance System (SEBS) model. Multivariate regression analyses were used to differentiate the contribution of climate and vegetation coverage to ET. The results showed that the annual average vegetation coverage significantly increased over time with a mean of 0.69 in spite of the precipitation fluctuation. Afforestation/reforestation and other management efforts attributed to vegetation coverage increase in NW Yunnan. Both ET and WY considerably fluctuated with the climate factors, which ranged from 623.29 mm to 893.8 mm and -51.88 mm to 384.40 mm over the time period. Spatially, ET in the southeast of NW Yunnan (mainly in Lijiang) increased significantly, which was in line with the spatial trend of vegetation coverage. Multivariate linear regression analysis indicated that climatic factors accounted for 85.18% of the ET variation, while vegetation coverage explained 14.82%. On the other hand, precipitation accounted for 67.5% of the WY. We conclude that the continuous droughts in northwest Yunnan were primarily climatically driven; however, man-made land cover and vegetation changes also increased the vulnerability of local populations to drought. Because of the high proportion of the water yield consumed for subsistence and poor infrastructure for water management, local populations have been highly vulnerable to climate drought conditions. We suggest that conservation of native vegetation and development of water-conserving agricultural practices should be implemented as adaptive strategies to mitigate climate change.

After several decades' development, meta-analysis has become the pillar of evidence-based medicine. However, heterogeneity is still the threat to the validity and quality of such studies. Currently, Q and its descendant I(2) (I square) tests are widely used as the tools for heterogeneity evaluation. The core mission of this kind of test is to identify data sets from similar populations and exclude those are from different populations. Although Q and I(2) are used as the default tool for heterogeneity testing, the work we present here demonstrates that the robustness of these two tools is questionable.We simulated a strictly normalized population S. The simulation successfully represents randomized control trial data sets, which fits perfectly with the theoretical distribution (experimental group: p = 0.37, control group: p = 0.88). And we randomly generate research samples Si that fits the population with tiny distributions. In short, these data sets are perfect and can be seen as completely homogeneous data from the exactly same population. If Q and I(2) are truly robust tools, the Q and I(2) testing results on our simulated data sets should not be positive. We then synthesized these trials by using fixed model. Pooled results indicated that the mean difference (MD) corresponds highly with the true values, and the 95% confidence interval (CI) is narrow. But, when the number of trials and sample size of trials enrolled in the meta-analysis are substantially increased; the Q and I(2) values also increase steadily. This result indicates that I(2) and Q are only suitable for testing heterogeneity amongst small sample size trials, and are not adoptable when the sample sizes and the number of trials increase substantially.Every day, meta-analysis studies which contain flawed data analysis are emerging and passed on to clinical practitioners as "updated evidence". Using this kind of evidence that contain heterogeneous data sets leads to wrong conclusion, makes chaos in clinical practice and weakens the foundation of evidence-based medicine. We suggest more strict applications of meta-analysis: it should only be applied to those synthesized trials with small sample sizes. We call upon that the tools of evidence-based medicine should keep up-to-dated with the cutting-edge technologies in data science. Clinical research data should be made available publicly when there is any relevant article published so the research community could conduct in-depth data mining, which is a better alternative for meta-analysis in many instances.

Understanding the influences of climatic changes on water use efficiency (WUE) of Tibetan alpine meadows is important for predicting their long-term net primary productivity (NPP) because they are considered very sensitive to climate change. Here, we collected wool materials produced from 1962 to 2010 and investigated the long-term WUE of an alpine meadow in Tibet on basis of the carbon isotope values of vegetation (δ13Cveg). The values of δ13Cveg decreased by 1.34‰ during 1962-2010, similar to changes in δ13C values of atmospheric CO2. Carbon isotope discrimination was highly variable and no trend was apparent in the past half century. Intrinsic water use efficiency (Wi) increased by 18 μmol·mol-1 (approximately 23.5%) during 1962-2010 because the increase in the intercellular CO2 concentration (46 μmol·mol-1) was less than that in the atmospheric CO2 concentration (Ca, 73 μmol·mol-1). In addition, Wi increased significantly with increasing growing season temperature and Ca. However, effective water use efficiency (We) remained relatively stable, because of increasing vapor pressure deficit. Ca, precipitation, and growing season temperature collectively explained 45% of the variation of We. Our findings indicate that the We of alpine meadows in the Tibetan Plateau remained relatively stable by physiological adjustment to elevated Ca and growing season temperature. These findings improve our understanding and the capacity to predict NPP of these ecosystems under global change scenarios.

In February 2013, H7N9 (A/H7N9/2013_China), a novel avian influenza virus, broke out in eastern China and caused human death. It is a global priority to discover its origin and the point in time at which it will become transmittable between humans. We present here an interdisciplinary method to track the origin of H7N9 virus in China and to establish an evolutionary dynamics model for its human-to-human transmission via mutations. After comparing influenza viruses from China since 1983, we established an A/H7N9/2013_China virus evolutionary phylogenetic tree and found that the human instances of virus infection were of avian origin and clustered into an independent line. Comparing hemagglutinin (HA) and neuraminidase (NA) gene sequences of A/H7N9/2013_China viruses with all human-to-human, avian, and swine influenza viruses in China in the past 30 years, we found that A/H7N9/2013_China viruses originated from Baer's Pochard H7N1 virus of Hu Nan Province 2010 (HA gene, EPI: 370846, similarity with H7N9 is 95.5%) and duck influenza viruses of Nanchang city 2000 (NA gene, EPI: 387555, similarity with H7N9 is 97%) through genetic re-assortment. HA and NA gene sequence comparison indicated that A/H7N9/2013_China virus was not similar to human-to-human transmittable influenza viruses. To simulate the evolution dynamics required for human-to-human transmission mutations of H7N9 virus, we employed the Markov model. The result of this calculation indicated that the virus would acquire properties for human-to-human transmission in 11.3 years (95% confidence interval (CI): 11.2-11.3, HA gene).

More than 50% of new drug candidates in drug discovery are lipophilic and exhibit poor aqueous solubility, which results in poor bioavailability and a lack of dose proportionality. Here, we improved the solubility of pedunculoside (PE) by generating a water-soluble inclusion complex composed of PE and the polymer β-cyclodextrin (CDP). We characterized this novel complex by 1H NMR, FT-IR, UV-vis spectroscopy, powder X-ray diffractometry and thermogravimetric analysis. The ratio of β-cyclodextrin (β-CD) units in CDP to PE was determined to be 2∶1. The KD value of the inclusion complex was determined to be 4.29×10(-3) mol•L(-1). In contrast to the low solubility of PE, the water-solubility of the PE-CDP complex was greatly enhanced. A preclinical toxicological study indicated that PE-CDP was well tolerated for a single administration. Importantly, the anti-inflammation potency of the PE-CDP complex was higher than that of PE. As a result, the formation of inclusion complexes by water-soluble CDP opens up possible aqueous applications of insoluble drug candidates in drug delivery.

AimsExcessively high left ventricle mass is an independent predictor of adverse prognosis. MicroRNAs (miRs) play crucial roles in the regulation of left ventricle hypertrophy (LVH). However, few circulating miRs have been established as predictors of LVH in aortic stenosis (AS) patients. In this study, we aimed to investigate whether circulating levels of miR-1, miR-133, and miR-378 predict LVH in patients with AS.Methods and resultsOne-hundred twelve patients with moderate to severe AS and 40 healthy controls were included in the study. Levels of miR-1, miR-133, and miR-378 in the plasma were measured by qPCR. Compared with healthy controls, AS patients had significantly lower circulating levels of miR-1, miR-133, and miR-378. AS patients with LVH had significantly lower miR-378 but not miR-1 and miR-133 compared with those without LVH. Linear regression analysis showed circulating miR-378 had strong correlation with left ventricular mass index (r = 0.283, p = 0.002) and logistic regression showed that lower miR-378 was an independent predictor for LVH in patients with AS (p = 0.037, OR 4.110, 95% CI 1.086 to 15.558).ConclusionCirculating levels of miR-1, miR-133 and miR-378 were decreased in AS patients, and miR-378 predicts LVH independent of the pressure gradient. Further prospective investigations are needed to elucidate whether these circulating miRs affect clinical outcome.

Spinal cord injury (SCI) is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR) screening, we identified 15 metabolites that made up an "Eigen-metabolome" capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.

OBJECTIVES: To assess erectile function in middle-aged and older men with asexuality status and further analyze their specific reasons for this condition. SUBJECTS AND METHODS: Men who had regular sexual intercourse attempts (sex frequency ≥ 1 time per month) were classified into mild erectile dysfunction (ED), moderate to severe ED and non-ED according to International Index of Erectile Function-5, and men having no sexual intercourse attempts for at least 6 months were defined as having an asexuality status. The risk factors associated with ED were collected in a sample of 1,531 Chinese men aged 40 to 80 years, and the self-report reasons for asexuality were recorded in asexual cohort individually. Comparative analyses and multivariate regression models were conducted among these groups. RESULTS: The prevalence rates of ED and asexuality status were 49.9% and 37.2%. The asexuality status group had higher risk factors than the moderate to severe ED group in terms of old age (age ≥ 65, adjusted odds ratio (OR) 17.69 versus (Vs.) 7.19), diabetes (crude OR: 2.40 Vs. 2.36) and hypertension (crude OR: 1.78 Vs. 1.72). The specific reasons for the asexuality status were "erectile difficulty" (52.9%), "do not care about sexuality" (53.5%)", "no longer necessary to have sexuality at this age" (47.7%), "severe stress" (44.4%), "severe fatigue" (26.3%) and "masturbation" (26.9%). CONCLUSIONS: Men with an asexual status suffer from higher risk factors for ED than men with moderate to severe ED. The majority of this asexual status could be attributed to a full ED, although the reasons for this transient asexuality also involved sexual attitudes and interests, sexual partners and masturbation.

We investigated avian influenza infections in wild birds, poultry, and humans at Eastern Dongting Lake, China. We analyzed 6,621 environmental samples, including fresh fecal and water samples, from wild birds and domestic ducks that were collected from the Eastern Dongting Lake area from November 2011 to April 2012. We also conducted two cross-sectional serological studies in November 2011 and April 2012, with 1,050 serum samples collected from people exposed to wild birds and/or domestic ducks. Environmental samples were tested for the presence of avian influenza virus (AIV) using quantitative PCR assays and virus isolation techniques. Hemagglutination inhibition assays were used to detect antibodies against AIV H5N1, and microneutralization assays were used to confirm these results. Among the environmental samples from wild birds and domestic ducks, AIV prevalence was 5.19 and 5.32%, respectively. We isolated 39 and 5 AIVs from the fecal samples of wild birds and domestic ducks, respectively. Our analysis indicated 12 subtypes of AIV were present, suggesting that wild birds in the Eastern Dongting Lake area carried a diverse array of AIVs with low pathogenicity. We were unable to detect any antibodies against AIV H5N1 in humans, suggesting that human infection with H5N1 was rare in this region.

PURPOSE: To evaluate the protective effects of bortezomib (Velcade) on ischemia-reperfusion (IR) injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg), or high-dose bortezomib (0.2 mg/kg) before the induction of IR injury. Electroretinography (ERG) was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α), anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin), and pro-apoptotic proteins (p53, bax) were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein), NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

Tumor-homing peptides that recognize specific markers on tumor cells have shown potential as drug carriers for targeted cancer therapy. Bombesin receptors are frequently overexpressed or ectopically expressed in a wide range of human tumors. Bombesin and its analogues have been widely used as drug carriers for tumor imaging and tumor therapy. However, the cargos used in previous studies, including radioactive and chemotherapeutic agents, are usually small molecules. Mitochondrial-disrupting peptides depolarize the mitochondria and trigger apoptosis after entering tumor cells. We are interested in whether the bombesin analogue, Bn(6-14), which contains a bombesin receptor-binding motif, can specifically deliver the mitochondria-disrupting peptide, B28, to tumor cells. To this end, we created a chimeric peptide, B28Bn(6-14), by conjugating B28 to Bn(6-14) at its N-terminus. The cytotoxicity of B28Bn(6-14) in tumor cells was much stronger than unconjugated B28. The IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) were approximately 10 times lower than B28. However, conjugation of B28 to Bn(2-7), which lacks the bombesin receptor-binding motif, did not increase its cytotoxicity. In addition, the IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) was 3-10 times lower than in normal cells (10.8-16.8 µM). We found that selective binding of B28Bn(6-14) to tumor cells is Bn(6-14)-dependent. Upon entering the tumor cell, B28Bn(6-14) accumulated in the mitochondria and triggered caspase-dependent apoptosis. Intratumoral and intraperitoneal administration of B28Bn(6-14) substantially suppressed the growth of DU145 tumor xenografts in mice. These results demonstrate that Bn(6-14) is able to deliver the mitochondria-disrupting peptide to tumor cells, and B28Bn(6-14) should be further developed as novel anti-cancer agent.

This study investigated the therapeutic potential and mechanisms of chitosan oligosaccharides (COS) for oxidative stress-induced retinal diseases. Retinal oxidative damage was induced in Sprague-Dawley rats by intravitreal injection of paraquat (PQ). Low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS was intragastrically given for 14 days after PQ injection. Electroretinograms were performed to determine the functionality of the retinas. The surviving neurons in the retinal ganglion cell layer and retinal apoptosis were determined by counting Neu N-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS) was determined by lucigenin- and luminol-enhanced chemiluminescence. Retinal oxidative damages were assessed by staining with nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical studies were used to demonstrate the expression of nuclear factor-kappa B (NF-κB) p65 in retinas. An in vitro study using RGC-5 cells was performed to verify the results. We demonstrated COS significantly enhanced the recovery of retinal function, preserved inner retinal thickness, and decreased retinal neurons loss in a dose-dependent manner. COS administration demonstrated anti-oxidative effects by reducing luminol- and lucigenin-dependent chemiluminenscense levels and activating superoxide dismutase and catalase, leading to decreased retinal apoptosis. COS markedly reduced retinal NF-κB p65. An in vitro study demonstrated COS increased IκB expression, attenuated the increase of p65 and thus decreased NF-κB/DNA binding activity in PQ-stimulated RGC-5 cells. In conclusion, COS attenuates oxidative stress-induced retinal damages, probably by decreasing free radicals, maintaining the activities of anti-oxidative enzymes, and inhibiting the activation of NF-κB.