Search

Muscle fatigue is one of the leading causes that contributes tremendously to injuries among volunteer firefighters in the workplace. The purpose of this study was to investigate the impact of positive-pressure breathing apparatus on muscle fatigue in the shoulder, back, and legs of volunteer firefighters. A total of 60 volunteer firefighters were recruited to perform a running task on a motorized treadmill in a controlled laboratory environment. Surface electromyography and rating of perceived exertion scores were collected from all participants every 60 seconds during the running task. Results show that the median frequency values for all measured muscle groups were significantly lower, and the rating of perceived exertion score was significantly higher after running with the positive-pressure breathing apparatus. Meanwhile, there were no significant differences in the median frequency values for the upper trapezius, erector spinae, and biceps femoris between the initial and final periods of running task without load. However, the median frequency values with load for gastrocnemius, rectus femoris, and tibialis anterior exhibited a greater downward trend compared to those without load. Additionally, using a breathing apparatus can cause asymmetric muscle fatigue in bilateral upper trapezius, erector spinae, gastrocnemius, and tibialis anterior muscles. The decreased performance due to muscle fatigue increases the risk of accidents, thereby posing a threat to the safety of volunteer firefighters. This study offers valuable insights into the effects of positive-pressure breathing apparatus on muscle fatigue among volunteer firefighters. These results may serve as a reference for developing improved fatigue management strategies and optimizing the design features of breathing apparatus.

Singing voice separation on robots faces the problem of interpreting ambiguous auditory signals. The acoustic signal, which the humanoid robot perceives through its onboard microphones, is a mixture of singing voice, music, and noise, with distortion, attenuation, and reverberation. In this paper, we used the 3D Inception-ResUNet structure in the U-shaped encoding and decoding network to improve the utilization of the spatial and spectral information of the spectrogram. Multiobjectives were used to train the model: magnitude consistency loss, phase consistency loss, and magnitude correlation consistency loss. We recorded the singing voice and accompaniment derived from the MIR-1K dataset with NAO robots and synthesized the 10-channel dataset for training the model. The experimental results show that the proposed model trained by multiple objectives reaches an average NSDR of 11.55 dB on the test dataset, which outperforms the comparison model.

Introduction Tranexamic acid (TXA) has been proven to prevent thrombolysis and reduce bleeding and blood transfusion requirements in various surgical settings. However, the optimal dose of TXA that effectively reduce intraoperative bleeding and blood product infusion in patients undergoing neurosurgical resection of meningioma with a diameter ≥ 5 cm remains unclear. Methods This is a single-center, randomized, double-blinded, paralleled-group controlled trial. Patients scheduled to receive elective tumor resection with meningioma diameter ≥ 5 cm will be randomly assigned the high-dose TXA group, the low-dose group, and the placebo. Patients in the high-dose TXA group will be administered with a loading dose of 20 mg/kg TXA followed by continuous infusion TXA at a rate of 5 mg/kg/h. In the low-dose group, patients will receive the same loading dose of TXA followed by a continuous infusion of normal saline. In the control group, patients will receive an identical volume of normal saline. The primary outcome is the estimated intraoperative blood loss calculated using the following formula: collected blood volume in the suction canister (mL)–the volume of flushing (mL) + the volume from the gauze tampon (mL). Secondary outcomes include calculated intraoperative blood loss, intraoperative coagulation function assessed using thromboelastogram (TEG), intraoperative cell salvage use, blood product infusion, and other safety outcomes. Discussion Preclinical studies suggest that TXA could reduce intraoperative blood loss, yet the optimal dose was controversial. This study is one of the early studies to evaluate the impact of intraoperative different doses infusion of TXA on reducing blood loss in neurological meningioma patients. Trial registration ClinicalTrials.gov, NCT05230381. Registered on February 8, 2022.

Bone fracture is an extremely dangerous health risk to human. Actually, cortical bone is often subjected to the complicated loading patterns. The mechanical properties and deformation mechanism under the complicated loading pattern could provide a more precise understanding for the bone fracture. For this purpose, the mechanical response and multi-scale deformation mechanism of cortical bone material were investigated by in-situ experimental research using the compression-torsion coupling loads as an example. It was found that the torsion strength and shear modulus all decreased under the compression-torsion coupling loads than single torsion load. This indicated bone would suffer greater risk of fracture under the compression-torsion coupling loads. Based on in-situ observation, it was found that the rapid reduction of the anisotropy of bone material under the compression load was the potential influencing factor. Because of the redistribution of the principal strain and the variations of cracks propagation, the comprehensive fracture pattern containing both transverse and longitudinal fracture was shown under the coupling loads, and finally resulted in the reduction of the torsion properties. This research could provide new references for researches on mechanical properties of cortical bone material under complicated loading patterns.

Bone fracture is an extremely dangerous health risk to human. Actually, cortical bone is often subjected to the complicated loading patterns. The mechanical properties and deformation mechanism under the complicated loading pattern could provide a more precise understanding for the bone fracture. For this purpose, the mechanical response and multi-scale deformation mechanism of cortical bone material were investigated by in-situ experimental research using the compression-torsion coupling loads as an example. It was found that the torsion strength and shear modulus all decreased under the compression-torsion coupling loads than single torsion load. This indicated bone would suffer greater risk of fracture under the compression-torsion coupling loads. Based on in-situ observation, it was found that the rapid reduction of the anisotropy of bone material under the compression load was the potential influencing factor. Because of the redistribution of the principal strain and the variations of cracks propagation, the comprehensive fracture pattern containing both transverse and longitudinal fracture was shown under the coupling loads, and finally resulted in the reduction of the torsion properties. This research could provide new references for researches on mechanical properties of cortical bone material under complicated loading patterns.

Joint roughness coefficients (JRCs) influence the shear and characteristic strengths of structural planes; however, the relationship model of this influence is yet to be derived. This study investigates 11 numerical simulation programs using a realistic failure process analysis software. The influence of size and JRC on the shear strengths of the structural planes was studied. The stress-strain curves of different JRCs and their sizes were analyzed. Mathematical models of the shear strength of structural planes and JRC and sizes were formulated and proposed, and their expressions were obtained. Moreover, mathematical models of JRC and the characteristic size and strength of the structural planes were established.

ObjectiveTo investigate the risk factors for metabolic bone disease of prematurity (MBDP), and to provide a reference for the prevention of MBDP.MethodsThe databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, Cochrane Library and other databases were searched for studies on the risk factors for MBDP published up to June 18, 2021. RevMan 5.3 and Stata 14.1 software were used to perform a Meta analysis.ResultsA total of 15 articles were included, including 13 case-control studies, 1 current investigation, and 1 retrospective cohort study. There were 1,435 cases in the case group and 2,057 cases in the control group, with a total sample size of 3,492 cases. Meta analysis showed that risk factors for MBDP include birth weight ConclusionFactors like birth weight

Semantic segmentation of medical images provides an important cornerstone for subsequent tasks of image analysis and understanding. With rapid advancements in deep learning methods, conventional U-Net segmentation networks have been applied in many fields. Based on exploratory experiments, features at multiple scales have been found to be of great importance for the segmentation of medical images. In this paper, we propose a scale-attention deep learning network (SA-Net), which extracts features of different scales in a residual module and uses an attention module to enforce the scale-attention capability. SA-Net can better learn the multi-scale features and achieve more accurate segmentation for different medical image. In addition, this work validates the proposed method across multiple datasets. The experiment results show SA-Net achieves excellent performances in the applications of vessel detection in retinal images, lung segmentation, artery/vein(A/V) classification in retinal images and blastocyst segmentation. To facilitate SA-Net utilization by the scientific community, the code implementation will be made publicly available.

ObjectiveHyperbilirubinemia is a common disease in the neonatal period, and hyperbilirubinemia may cause brain damage. Therefore, prevention and diagnosis and management of hyperbilirubinemia is very important, and vitamin D may affect bilirubin levels. To evaluate the relationship between neonatal hyperbilirubinemia and vitamin D levels.MethodThe China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and Embase databases as well as clinical trial registries in China and the United States were searched for relevant studies from inception to September 2020 without restrictions on language, population, or year. The studies was screened by two reviewers independently, the data were extracted, and the risk of bias of the included studies was evaluated using the NOS. A meta-analysis was conducted on the included studies using Stata11 software.ResultsSix case-control studies were included, and the methodological quality of the studies was high (grade A). The studies included 690 newborns; more than 409 were diagnosed with hyperbilirubinemia. The means and standard deviations were calculated. Meta-analysis results showed that neonatal vitamin D levels were 7.1 ng/ml lower among infants with hyperbilirubinemia than among healthy newborn levels (z = 6.95, 95% CI 9.10 ~ 5.09, P < 0.05). Subgroup analysis was conducted based on whether the bilirubin levels were concentrated in the 15 to 20 mg/dl range. Vitamin D level of infants with hyperbilirubinemia (the bilirubin levels were concentrated in the 15 to 20 mg/dl range) was 9.52 ng/ml (Z = 15.55, 95% CI-10.72~-8.32, PConclusionVitamin D levels were observed to be lower in neonates with hyperbilirubinemia as compared to term neonates without hyperbilirubinemia in this study. This can possibly suggest that neonates with lower vitamin D levels are at higher risk for developing hyperbilirubinemia.

ObjectiveTo explore the influence of biological characteristics on the yield of Amomum villosum Lour. and Amomum longiligulare T. L. Wu, to find an effective pollen viability evaluation method and storage method to solve the problem of the low yield of Amomum plants.MethodsFive germplasm of Amomum plants were used to investigate the effects of the phenological phase, pollen viability, and stigma receptivity on natural and artificial fruit set.ResultsAmomum longiligulare T. L. Wu showed late flowering, and its natural pollination rate is higher than that of Amomum villosum Lour. In all germplasm, the artificial pollination rate and fruit setting rate are more than 3 times higher than that under natural conditions. Fruits begin to drop seven days after successful pollination, and the fruit drop is basically stable after one month. The hybridization verification showed that TTC method was simpler and more accurate than in vitro germination method. Optimal storage conditions for pollen are 4°C and high humidity. After 36 h of storage, pollen can still be used for artificial cross-pollination or as hybrid parents.ConclusionThe special biological characteristics are the fundamental reason for the low natural pollination rate of Amomum plants. The accurate measurement method of Amomum plants pollen is the TTC method, and storage at 4°C and high humidity can increase the yield, which was six times that of the natural yield.

Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- subtype, and their functional role in the regulation of miRNA expression, especially among high risk AA women. In this study, we evaluated DNA methylation patterns of miRNA encoding genes and their effect on expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, corresponding to 2,035 unique mature miRNAs. We identified differentially methylated loci (DMLs: (|delta β|)>0.10, FDR

In December 2019, the novel coronavirus pneumonia (COVID-19) occurred in Wuhan, Hubei Province, China. The epidemic quickly broke out and spread throughout the country. Now it becomes a pandemic that affects the whole world. In this study, three models were used to fit and predict the epidemic situation in China: a modified SEIRD (Susceptible-Exposed-Infected-Recovered-Dead) dynamic model, a neural network method LSTM (Long Short-Term Memory), and a GWR (Geographically Weighted Regression) model reflecting spatial heterogeneity. Overall, all the three models performed well with great accuracy. The dynamic SEIRD prediction APE (absolute percent error) of China had been ≤ 1.0% since Mid-February. The LSTM model showed comparable accuracy. The GWR model took into account the influence of geographical differences, with R2 = 99.98% in fitting and 97.95% in prediction. Wilcoxon test showed that none of the three models outperformed the other two at the significance level of 0.05. The parametric analysis of the infectious rate and recovery rate demonstrated that China's national policies had effectively slowed down the spread of the epidemic. Furthermore, the models in this study provided a wide range of implications for other countries to predict the short-term and long-term trend of COVID-19, and to evaluate the intensity and effect of their interventions.

Online shopping behavior has the characteristics of rich granularity dimension and data sparsity and presents a challenging task in e-commerce. Previous studies on user behavior prediction did not seriously discuss feature selection and ensemble design, which are important to improving the performance of machine learning algorithms. In this paper, we proposed an SE-stacking model based on information fusion and ensemble learning for user purchase behavior prediction. After successfully using the ensemble feature selection method to screen purchase-related factors, we used the stacking algorithm for user purchase behavior prediction. In our efforts to avoid the deviation of the prediction results, we optimized the model by selecting ten different types of models as base learners and modifying the relevant parameters specifically for them. Experiments conducted on a publicly available dataset show that the SE-stacking model can achieve a 98.40% F1 score, approximately 0.09% higher than the optimal base models. The SE-stacking model not only has a good application in the prediction of user purchase behavior but also has practical value when combined with the actual e-commerce scene. At the same time, this model has important significance in academic research and the development of this field.

There are a few well-known indigenous breeds of Chinese rabbits in Sichuan and Fujian provinces, for which the genetic diversity and population structure have been poorly investigated. In the present study, we successfully employed the restriction-site-associated DNA sequencing (RAD-seq) approach to comprehensively discover genome-wide SNPs of 104 rabbits from four Chinese indigenous breeds: 30 Sichuan White, 34 Tianfu Black, 32 Fujian Yellow and eight Fujian Black. A total of 7,055,440 SNPs were initially obtained, from which 113,973 high-confidence SNPs (read depth ≥ 3, calling rate = 100% and biallelic SNPs) were selected to study the genetic diversity and population structure. The mean polymorphism information content (PIC) and nucleotide diversity (π) of each breed slightly varied with ranging from 0.2000 to 0.2281 and from 0.2678 to 0.2902, respectively. On the whole, Fujian Yellow rabbits showed the highest genetic diversity, which was followed by Tianfu Black and Sichuan White rabbits. The principal component analysis (PCA) revealed that the four breeds were clearly distinguishable. Our results first reveal the genetic differences among these four rabbit breeds in the Sichuan and Fujian provinces and also provide a high-confidence set of genome-wide SNPs for Chinese indigenous rabbits that could be employed for gene linkage and association analyses in the future.

Gliomas are the most common malignant tumors of the brain and are characteristic of severe migration and invasion. Glial cell line-derived neurotrophic factor (GDNF) promotes glioma development process. However, the regulatory mechanisms of promoting occurrence and development of glioma have not yet been clearly elucidated. In the present study, the mechanism by which GDNF promotes glioma cell migration and invasion through regulating the dispersion and location of the Golgi apparatus (GA) is described. Following GDNF treatment, a change in the volume and position of GA was observed. The stack area of the GA was enlarged and it was more concentrated near the nucleus. Golgin-160 and Golgi microtubule-associated protein 210 (GMAP210) were identified as target molecules regulating GA positioning. In the absence of either golgin-160 or GMAP210 using lentivirus, the migration and invasion of U251 cells were decreased, while it was increased following GDNF. It was also found that the GA was decreased in size and dispersed following golgin-160 or GMAP210 knockdown, as determined by GA green fluorescence assay. Once GDNF was added, the above phenomenon would be twisted, and the concentrated location and volume of the GA was restored. In combination, the present data suggested that the regulation of the position and size of the GA by golgin-160 and GMAP210 play an important role in U251 cell migration and invasion.

BACKGROUND:To observe the effects of different treatments of lymph after intestinal I/R in rats on macrophages in vitro. METHODS:Forty-eight healthy SPF SD rats weighing 300 ± 20 g, were randomly divided into two groups: group A, and group B. The rats in group A were drained of lymph fluid for 180 min; the rats in group B were subjected to 60 min ischemia by clamping the SMA, followed by 120 min reperfusion and 180 min of lymph drainage. The lymph fluid collected was divided into 4 sub-groups: 1. no treatment (A1, Ly, and B1, I/R Ly); 2. protein degradation (A2, Ly PD, and B2 I/R PD); 3. endotoxin removal (A3, Ly ER, and B3, I/R ER); 4. protein degradation plus endotoxin removal (A4, Ly PD+ER, and B4, I/R PD+ER), then used to stimulate a monocyte-macrophage cell line. RESULTS:Compared with group A1, the levels of the inflammatory cytokines, chemokines, HMGB1 concentration, protein and mRNA expression of TLR4, HMGB1 and NF-κBp65 were significantly increased in group B1. There was a significant reduction in proinflammatory cytokines and of the expression of TLR4, NF-κBp65, and chemokines in groups A2, B2, A4, and B4. However, there were no significant decrease of these factors in groups A3 and B3. CONCLUSIONS:The lymph fluid drained after intestinal I/R can cause inflammation in vivo and in vitro. Deproteinization of lymph fluid with proteinase K significantly reduced the concentration of proinflammatory cytokines, chemokines, TLR4 and NF-κBp65 in cell culture supernatant, exerting a protective effect on inflammatory reaction caused by the intestinal I/R. Passage of lymph fluid through an endotoxin removal column did not reduce the levels of active proinflammatory factors produced by macrophages in vitro.

BackgroundMore than 11 million people were estimated to be infected by Schistosoma japonicum in China before the 1950s. However, seldom studies have been conducted to evaluate the longitudinal effects of previous schistosome infection (PSI). We aimed to investigate the association between PSI and hyperuricemia in China.MethodsFrom February 2013 to October 2013, 3,517 Chinese subjects (908 persons with PSI and 2,609 persons without PSI) were recruited from a prospective cohort study of "135". After two years, 113 and 462 participants had developed hyperuricemia in the persons with and without PSI, respectively. Multivariable logistic models were used to estimate Relative Ratios (RR) and 95% confidence intervals (CIs) for hyperuricemia.ResultsThe PSI participants had a decreased risk of hyperuricemia compared with those without PSI [adjusted RR (95%CI): 0.73 (0.55, 0.97)]. Within the PSI group, higher level of fasting plasma glucose was significantly associated with the reduced incidence of hyperuricemia in PSI population (RR: 0.40, 95% CI: 0.26-0.63). For females, hypertension, increased levels of serum creatinine and triglycerides were the risk factors for incident hyperuricemia in the PSI group.ConclusionsOur results suggest that PSI is significantly associated with the lower incidence of hyperuricemia. Moreover, elevated fasting plasma glucose might prevent the onset of hyperuricemia in PSI population.

It is widely acknowledged that phonemic segments are primary phonological units, processed serially, in spoken word production of Germanic languages. However, evidence for a behavioural effect of single-segment overlap on Chinese spoken word production is lacking. The current study adopted the form-preparation paradigm to investigate the effects of segment predictability and segment repetition separately, which were mixed in previous studies. Native Mandarin Chinese speakers named pictures in the following conditions: predictable, unpredictable, and no segment repetition. Different positions in words (i.e., the onset and the rhyme) were examined at the same time. Results revealed a facilitation effect of onset predictability masked by an inhibition tendency of onset repetition, indicating Chinese speakers' ability to prepare the predictable onset. In contrast, rhyme predictability showed a non-significant effect. This pattern of results did not change no matter whether the conditions of unpredictable onset repetition and unpredictable rhyme repetition were mixed in the same context (Experiment 1) or extracted from different blocked contexts (Experiment 2). The finding provides essential support to the claim that phonemic segments are functionally engaged in Chinese spoken word production, and thus adds original evidence to the universal aspect of spoken word production.

Samia cynthia ricini (Lepidoptera: Saturniidae) is an important commercial silk-producing insect; however, in contrast to the silkworm, mulberry leaves are toxic to this insect because the leaves contain the component 1-deoxynojirimycin (DNJ). A transcriptomic analysis of eri-silkworm haemolymph was conducted to examine the genes related to different metabolic pathways and to elucidate the molecular mechanism underlying eri-silkworm haemolymph responses to DNJ. Eight hundred sixty-five differentially expressed genes (DEGs) were identified, among which 577 DEGs were up-regulated and 288 DEGs were down-regulated in the 2% DNJ group compared to control (ddH2O) after 12h. Based on the results of the functional analysis, these DEGs were associated with ribosomes, glycolysis, N-glycan biosynthesis, and oxidative phosphorylation. In particular, according to the KEGG analysis, 138 DEGs were involved in energy metabolism, glycometabolism and lipid metabolism, and the changes in the expression of nine DEGs were confirmed by reverse transcription quantitative PCR (RT-qPCR). Thus, DNJ induced significant metabolic alterations in eri-silkworm haemolymph. These results will lay the foundation for research into the toxic effects of DNJ on eri-silkworm as a model and provide a reference for the exploitation of new drugs in humans.

BACKGROUND AND AIMS:The clinical value of the prognostic nutritional index (PNI) in hepatocellular carcinoma (HCC) has been investigated in previous studies, but the results remain controversial. Here we present a meta-analysis to systematically review the association between PNI and HCC prognosis. METHOD:PubMed, EMBASE, Web of Science databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to determine the prognostic and clinic-pathological values of PNI in HCC patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the association of PNI with survival and clinic-pathological characteristics, respectively. RESULTS:A total of eleven studies involving 3165 patients were analyzed. The pooled results indicated that low PNI is a significant predictor of poor 1-year, 3-year, 5-year OS (OR, 2.91, 4.05, 3.65; 95%CI, 2.30 to 3.70, 3.27 to 5.03,2.96-4.50; P = 0.14,0.22,0.11 respectively) and disease-free survival (DFS) (OR,2.35, 2.57, 2.75; 95%CI, 1.71 to 3.23, 1.89 to 3.49,2.01 to 3.75; P = 0.39,0.04,0.11, respectively). Moreover, PNI is significantly associated with serum AFP, tumor recurrence, tumor size and TNM stages in HCC patients. However, PNI is not significantly associated with tumor number and the incidence of cirrhosis in HCC patients. CONCLUSIONS:PNI is an independent predictive indicator of survival and associated with serum AFP, tumor recurrence, tumor size and TNM stages in HCC patients.

Two experiments were conducted to investigate the time course of syllabic and sub-syllabic processing in Cantonese spoken word production by using the picture-word interference task. Cantonese-speaking participants were asked to name individually presented pictures aloud and ignore an auditory word distractor. The targets and distractors were either phonologically related (i.e., sharing two identical word-initial phonemes) or unrelated. In Experiment 1, the target syllables were all consonant-vowel (CV)-structured. The phonological distractor was either a CV syllable (i.e., Full Syllable Overlap) or a CVC (consonant-vowel-consonant) syllable (i.e., Sub-syllable Overlap). Relative to the unrelated control, Full Syllable Overlap distractors facilitated naming in all stimuli onset asynchronies (SOAs) (-175, 0, or +175 ms) whereas Sub-syllable Overlap distractors exhibited facilitation only at 0-ms and +175-ms SOAs. Experiment 2 adopted a similar design to examine the possible influence of syllabic structure similarity on the results of Experiment 1. The target syllables were all CVC-structured. The phonological distractor was either a CVC (i.e., Syllable-structure Consistent) or CV (i.e., Syllable-structure Inconsistent) syllable. Comparable priming was observed between the two distractor conditions across the three SOAs. These results indicated that an earlier priming effect was observed with full syllable overlap than sub-syllabic overlap when the degree of segmental overlap was held constant (Experiment 1). The earlier syllable priming observed in Experiment 1 could not be attributed to the effect of syllabic-structure (Experiment 2), thereby suggesting that the syllable unit is important in Cantonese and is retrieved earlier than sub-syllabic components during phonological encoding.

Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships.

Feed represents the major cost of chicken production. Selection for improving feed utilization is a feasible way to reduce feed cost and greenhouse gas emissions. The objectives of this study were to investigate the efficiency of genomic prediction for feed conversion ratio (FCR), residual feed intake (RFI), average daily gain (ADG) and average daily feed intake (ADFI) and to assess the impact of selection for feed efficiency traits FCR and RFI on eviscerating percentage (EP), breast muscle percentage (BMP) and leg muscle percentage (LMP) in meat-type chickens. Genomic prediction was assessed using a 4-fold cross-validation for two validation scenarios. The first scenario was a random family sampling validation (CVF), and the second scenario was a random individual sampling validation (CVR). Variance components were estimated based on the genomic relationship built with single nucleotide polymorphism markers. Genomic estimated breeding values (GEBV) were predicted using a genomic best linear unbiased prediction model. The accuracies of GEBV were evaluated in two ways: the correlation between GEBV and corrected phenotypic value divided by the square root of heritability, i.e., the correlation-based accuracy, and model-based theoretical accuracy. Breeding values were also predicted using a conventional pedigree-based best linear unbiased prediction model in order to compare accuracies of genomic and conventional predictions. The heritability estimates of FCR and RFI were 0.29 and 0.50, respectively. The heritability estimates of ADG, ADFI, EP, BMP and LMP ranged from 0.34 to 0.53. In the CVF scenario, the correlation-based accuracy and the theoretical accuracy of genomic prediction for FCR were slightly higher than those for RFI. The correlation-based accuracies for FCR, RFI, ADG and ADFI were 0.360, 0.284, 0.574 and 0.520, respectively, and the model-based theoretical accuracies were 0.420, 0.414, 0.401 and 0.382, respectively. In the CVR scenario, the correlation-based accuracy and the theoretical accuracy of genomic prediction for FCR was lower than RFI, which was different from the CVF scenario. The correlation-based accuracies for FCR, RFI, ADG and ADFI were 0.449, 0.593, 0.581 and 0.627, respectively, and the model-based theoretical accuracies were 0.577, 0.629, 0.631 and 0.638, respectively. The accuracies of genomic predictions were 0.371 and 0.322 higher than the conventional pedigree-based predictions for the CVF and CVR scenarios, respectively. The genetic correlations of FCR with EP, BMP and LMP were -0.427, -0.156 and -0.338, respectively. The correlations between RFI and the three carcass traits were -0.320, -0.404 and -0.353, respectively. These results indicate that RFI and FCR have a moderate accuracy of genomic prediction. Improving RFI and FCR could be favourable for EP, BMP and LMP. Compared with FCR, which can be improved by selection for ADG in typical meat-type chicken breeding programs, selection for RFI could lead to extra improvement in feed efficiency.

Estimation of evapotranspiration (ET) for alpine meadow areas in the Tibetan Plateau (TP) is essential for water resource management. However, observation data has been limited due to the extreme climates and complex terrain of this region. To address these issues, four representative methods, Penman-Monteith (PM), Priestley-Taylor (PT), Hargreaves-Samani (HS), and Mahringer (MG) methods, were adopted to estimate ET, which were then compared with ET measured using Eddy Covariance (EC) for five alpine meadow sites during the growing seasons from 2010 to 2014. And each site was measured for one growing season during this period. The results demonstrate that the PT method outperformed at all sites with a coefficient of determination (R2) ranging from 0.76 to 0.94 and root mean square error (RMSE) ranging from 0.41 to 0.62 mm d-1. The PM method showed better performance than HS and MG methods, and the HS method produced relatively acceptable results with higher R2 (0.46) and lower RMSE (0.89 mm d-1) compared to MG method with R2 of 0.16 and RMSE of 1.62 mm d-1, while MG underestimated ET at all alpine meadow sites. Therefore, the PT method, being the simpler approach and less data dependent, is recommended to estimate ET for alpine meadow areas in the Tibetan Plateau. The PM method produced reliable results when available data were sufficient, and the HS method proved to be a complementary method when variables were insufficient. On the contrary, the MG method always underestimated ET and is, thus, not suitable for alpine meadows. These results provide a basis for estimating ET on the Tibetan Plateau for annual data collection, analysis, and future studies.

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevation of serum cholesterol bound to low-density lipoprotein. Mutations in LDLR are the major factors responsible for FH. In this study, we recruited a four-generation Chinese family with FH and identified the clinical features of hypercholesterolemia. All affected individuals shared a novel indel mutation (c.1885_1889delinsGATCATCAACC) in exon 13 of LDLR. The mutation segregated with the hypercholesterolemia phenotype in the family. To analyze the function of the indel, we established stable clones of mutant and wild-type LDLR in Hep G2 cells. The mutant LDLR was retained in the endoplasmic reticulum (ER) and failed to glycosylate via the Golgi. Moreover, the membrane LDLR was reduced and lost the ability to take up LDL. Our data also expand the spectrum of known LDLR mutations.

BACKGROUND:Hybrid weakness, a phenomenon opposite to heterosis, refers to inferior growth and development in a hybrid relative to its pure-line parents. Little attention has been paid to the phenomenological or mechanistic aspect of hybrid weakness, probably due to its rare occurrence. METHODOLOGY/PRINCIPAL FINDINGS:Here, using a set of interspecific triploid F1 hybrids between Oryza sativa, ssp. japonica (genome AA) and a tetraploid wild rice species, O. alta (genome, CCDD), we investigated the phenotypic and physiological differences between the F1 hybrids and their parents under normal and nitrogen-limiting conditions. We quantified the expression levels of 21 key genes involved in three important pathways pertinent to the assayed phenotypic and physiological traits by real-time qRT-PCR. Further, we assayed expression partitioning of parental alleles for eight genes in the F1 hybrids relative to the in silico "hybrids" (parental cDNA mixture) under both normal and N-limiting conditions by using locus-specific cDNA pyrosequencing. CONCLUSIONS/SIGNIFICANCE:We report that the F1 hybrids showed weakness in several phenotypic traits at the final seedling-stage compared with their corresponding mid-parent values (MPVs). Nine of the 21 studied genes showed contrasted expression levels between hybrids and parents (MPVs) under normal vs. N-limiting conditions. Interestingly, under N-limiting conditions, the overtly enhanced partitioning of maternal allele expression in the hybrids for eight assayed genes echo their attenuated hybrid weakness in phenotypes, an observation further bolstered by more resemblance of hybrids to the maternal parent under N-limiting conditions compared to normal conditions in a suite of measured physiological traits. Our observations suggest that both overall expression level and differential partitioning of parental alleles of critical genes contribute to condition-specific hybrid weakness.

Metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic syndromes (MetS) have been recognized as the important risk factors for asymptomatic intracranial vertebrobasilar stenosis (IVBS). Although fatty liver index (FLI) is significantly related with these diseases, the association between FLI and IVBS remains unclear. In the present study, 2368 participants (30-75 years) were recruited from a Chinese prospective cohort study of PMMJS. Amongst them, 2281 individuals who did not have IVBS at baseline were enrolled in the 6-year following-up study. In cross-sectional analysis based on the baseline characteristics, the results showed that FLI was positively related with IVBS prevalence. Compared to the participants with FLI < 30, the adjusted OR (95% CI) of IVBS was 2.07 (1.18, 3.62) and 2.85 (1.39, 5.18) in the groups of 30 ≤ FLI < 60 and FLI ≥ 60, respectively. In longitudinal analysis, the results showed that the participants with FLI ≥ 60 had an increased risk of asymptomatic IVBS compared to those with FLI < 30 [adjusted HR (95%CI): 1.65 (1.05, 2.60)]. Moreover, exclusion of persons with hypertension, T2DM and MetS did not alter the associations between FLI and asymptomatic IVBS. Therefore, our results suggest that elevated FLI is an independent risk factor for asymptomatic IVBS in Chinese adults.

BACKGROUND:Vitamin D deficiency has become prevalent worldwide in recent years. However, less evidence was available for lactating women. OBJECTIVE:The purpose of the study was to understand vitamin D status and prevalence of deficiency in lactating women and associated risk factors for vitamin D deficiency from eight provinces and municipalities in China. METHODS:Lactating women within 1-10 months postpartum were recruited in 2011-2013 from eight provinces and municipalities in China. Radioimmunoassay was used to measure serum 25-hydroxyvitamin D [25(OH)D] concentration. Standardized questionnaire was used to collect information on season, living site, ethnicity and socio-demographic characteristics. RESULTS:Totally 2004 lactating women were recruited. The median (p25, p75) of 25(OH)D was 15.8 (10.5, 24.0) nmol/L. The prevalence of vitamin D deficiency was 85.3% as 25(OH)D

BACKGROUND:Poor growth and micronutrient deficiency mainly attack older infants and young children. Some countries have adopted clinically effective measures to combat malnutrition, but the compliance and improvement in efficacy of intervention vehicles in national programs require evaluation. METHODS:Baseline and follow-up cross-sectional surveys were conducted before and after a nutrition intervention program in 3 national poverty counties in China. Soybean-based complementary food supplements called Yingyangbao (YYB) in Chinese and training materials on child feeding were distributed to households with children aged 6-23 months for 18 months. Representative children were selected by probability proportional to size sampling methods to assess compliance of YYB and the intervention efficacy. A questionnaire was designed to collect data on basic characteristics of children, breastfeeding, 24-hour dietary intake, and consumption and appetite of YYB. Anthropometrics and hemoglobin were measured in the field, and anemia prevalence was evaluated. Venous blood was drawn from children aged 12-35 months to evaluate micronutrient status. Logistic regression was used to identify the risk factors for children's anemia. RESULTS:Of the children involved in the follow-up survey (n = 693), the P50 (P25, P75) intake of YYB was 6.7 (3.5, 7.0) sachets weekly, and 54.7% of the children liked the taste of YYB. Compared with the baseline situation (n = 823), the proportion of children fed a diverse diet and foods rich in iron or vitamin A increased (P < 0.01) in the follow-up study. The prevalence of stunting and underweight decreased (P < 0.05), the prevalence of anemia decreased from 28.0% to 19.9% (P < 0.01), and the prevalence of vitamin B12 deficiency decreased from 26.8% to 15.4% (P < 0.01). For children aged 12-23 months, those who liked YYB and consumed 6 or more sachets of YYB weekly were at lower risk for anemia (OR = 0.34, 95% CI 0.13-0.90, P < 0.05), but the risk of stunting was associated with a non-diverse diet (OR = 1.48, 95% CI 1.06-2.07, P < 0.05). CONCLUSION:The quality of diet and nutritional status of children aged 6-23 months are significantly improved by the intervention of YYB and nutrition education, and good compliance to YYB contributes to a low risk for anemia. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR-OOC-16008846.

Drosophila larvae exhibit klinotaxis when placed in a gradient of temperature, chemicals, or light. The larva samples environmental stimuli by casting its head from side to side. By comparing the results of two consecutive samples, it decides the direction of movement, appearing as a turn proceeded by one or more head casts. Here by analyzing larval behavior in a light-spot-based phototaxis assay, we showed that, in addition to turns with a single cast (1-cast), turns with multiple head casts (n-cast) helped to improve the success of light avoidance. Upon entering the light spot, the probability of escape from light after the first head cast was only ~30%. As the number of head casts increased, the chance of successful light avoidance increased and the overall chance of escaping from light increased to >70%. The amplitudes of first head casts that failed in light avoidance were significantly smaller in n-cast turns than those in 1-cast events, indicating that n-cast turns might be planned before completion of the first head cast. In n-casts, the amplitude of the second head cast was generally larger than that of the first head cast, suggesting that larvae tried harder in later attempts to improve the efficacy of light avoidance. We propose that both 1-cast turns and n-cast turns contribute to successful larval light avoidance, and both can be initiated at the first head cast.

ObjectiveTo evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).MethodsWe searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.ResultsWe included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.ConclusionsThere appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX.

BACKGROUND:Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. METHODS AND RESULTS:Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. CONCLUSION:Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries.

Muscle development and growth influences the efficiency of poultry meat production, and is closely related to deposition of intramuscular fat (IMF), which is crucial in meat quality. To clarify the molecular mechanisms underlying muscle development and IMF deposition in chickens, protein expression profiles were examined in the breast muscle of Beijing-You chickens at ages 1, 56, 98 and 140 days, using isobaric tags for relative and absolute quantification (iTRAQ). Two hundred and four of 494 proteins were expressed differentially. The expression profile at day 1 differed greatly from those at day 56, 98 and 140. KEGG pathway analysis of differential protein expression from pair-wise comparisons (day 1 vs. 56; 56 vs. 98; 98 vs. 140), showed that the fatty acid degradation pathway was more active during the stage from day 1 to 56 than at other periods. This was consistent with the change in IMF content, which was highest at day 1 and declined dramatically thereafter. When muscle growth was most rapid (days 56-98), pathways involved in muscle development were dominant, including hypertrophic cardiomyopathy, dilated cardiomyopathy, cardiac muscle contraction, tight junctions and focal adhesion. In contrast with hatchlings, the fatty acid degradation pathway was downregulated from day 98 to 140, which was consistent with the period for IMF deposition following rapid muscle growth. Changes in some key specific proteins, including fast skeletal muscle troponin T isoform, aldehyde dehydrogenase 1A1 and apolipoprotein A1, were verified by Western blotting, and could be potential biomarkers for IMF deposition in chickens. Protein-protein interaction networks showed that ribosome-related functional modules were clustered in all three stages. However, the functional module involved in the metabolic pathway was only clustered in the first stage (day 1 vs. 56). This study improves our understanding of the molecular mechanisms underlying muscle development and IMF deposition in chickens.

BACKGROUND:The purpose of the study is to elicit the epigenetic mechanism involving CCCTC binding factor (CTCF)-mediated chromatin remodeling that regulates PAX6 gene interaction with differentiation-associated genes to control corneal epithelial differentiation. METHODS:Cell cycle progression and specific keratin expressions were measured to monitor changes of differentiation-induced primary human limbal stem/progenitor (HLS/P), human corneal epithelial (HCE) and human telomerase-immortalized corneal epithelial (HTCE) cells. PAX6-interactive and differentiation-associated genes in chromatin remodeling mediated by the epigenetic factor CTCF were detected by circular chromosome conformation capture (4C) and ChIP (Chromatin immunoprecipitation)-on-chip approaches, and verified by FISH (Fluorescent in situ hybridization). Furthermore, CTCF activities were altered by CTCF-shRNA to study the effect of CTCF on mediating interaction of Pax6 and differentiation-associated genes in corneal epithelial cell fate. RESULTS:Our results demonstrated that differentiation-induced human corneal epithelial cells expressed typical corneal epithelial characteristics including morphological changes, increased keratin12 expression and G0/G1 accumulations. Expressions of CTCF and PAX6 were suppressed and elevated following the process of differentiation, respectively. During corneal epithelial cell differentiation, differentiation-induced RCN1 and ADAM17 were found interacting with PAX6 in the process of CTCF-mediated chromatin remodeling detected by 4C and verified by ChIP-on-chip and FISH. Diminished CTCF mRNA with CTCF-shRNA in HTCE cells weakened the interaction of PAX6 gene in controlling RCN1/ADAM17 and enhanced early onset of the genes in cell differentiation. CONCLUSION:Our results explain how epigenetic factor CTCF-mediated chromatin remodeling regulates interactions between eye-specific PAX6 and those genes that are induced/associated with cell differentiation to modulate corneal epithelial cell-specific differentiation.

A large proportion of mutants with altered pigment features have been obtained via exposure to heavy-ion beams, a technique that is efficient for trait improvement in the breeding of plants and algae. However, little is known about the underlying mechanisms by which the photosynthetic pigments are altered by heavy-ion irradiation. In our study, the photosynthetic characteristics of progenies from carbon-ion irradiated Selenastrum capricornutum were investigated. Five progenies deficient in chlorophyll a were isolated after carbon-ion exposure. Photosynthetic characteristics, photoprotection capacity and gene expression of the light-harvesting complex in these progenies were further characterized by the measurement of chlorophyll fluorescence parameters (Fv/Fm, ФPSII, NPQ, ETR), the de-epoxidation state of the xanthophyll cycle, the amount of lutein and quantitative real-time PCR. High maximum quantum yield of photosystem II at day 10 and high thermal dissipation ability were observed in progenies #23 and #37 under normal culture condition. Progenies #18, #19 and #20 showed stronger resistance against high levels of light steps than the control group (612-1077 μmol photons m -2 s -1, p< 0.05). The progenies #20 and #23 exhibited strong photoprotection by thermal dissipation and quenching of 3Chl* after 24 h of high light treatment. The mRNA levels of Lhcb5, Lhcbm5 and Lhcbm1 of the light-harvesting complex revealed markedly differential expression in the five progenies irradiated by carbon-ion beams. This work indicates that photosynthetic efficiency, photoprotection ability and the expression of light-harvesting antennae in unicellular green algae can be markedly influenced by irradiation. To our knowledge, this is the first report on changes in the photosynthetic pigments of green algae after treatment with carbon-ion beams.

Targeting modules or signalings may open a new path to understanding the complex pharmacological mechanisms of reversing disease processes. However, determining how to quantify the structural alteration of these signalings or modules in pharmacological networks poses a great challenge towards realizing rational drug use in clinical medicine. Here, we explore a novel approach for dynamic comparative and quantitative analysis of the topological structural variation of modules in molecular networks, proposing the concept of allosteric modules (AMs). Based on the ischemic brain of mice, we optimize module distribution in different compound-dependent modular networks by using the minimum entropy criterion and then calculate the variation in similarity values of AMs under various conditions using a novel method of SimiNEF. The diverse pharmacological dynamic stereo-scrolls of AMs with functional gradient alteration, which consist of five types of AMs, may robustly deconstruct modular networks under the same ischemic conditions. The concept of AMs can not only integrate the responsive mechanisms of different compounds based on topological cascading variation but also obtain valuable structural information about disease and pharmacological networks beyond pathway analysis. We thereby provide a new systemic quantitative strategy for rationally determining pharmacological mechanisms of altered modular networks based on topological variation.

Cdc14 is a dual-specificity phosphatase that regulates nuclear behavior by dephosphorylating phosphotyrosine and phosphoserine/phosphothreonine in fungi. Previously, Cdc14 was shown to act as a positive regulator of cytokinesis, asexual development and multiple stress responses in Beauveria bassiana, a fungal insect pathogen. This study seeks to gain deep insight into a pivotal role of Cdc14 in the signaling network of B. bassiana by analyzing the Cdc14-specific proteome and phosphoproteome generated by the 8-plex iTRAQ labeling and MS/MS analysis of peptides and phosphopeptides. Under normal conditions, 154 proteins and 86 phosphorylation sites in 67 phosphoproteins were upregulated in Δcdc14 versus wild-type, whereas 117 proteins and 85 phosphorylation sites in 58 phosphoproteins were significantly downregulated. Co-cultivation of Δcdc14 with NaCl (1 M), H2O2 (3 mM) and Congo red (0.15 mg/ml) resulted in the upregulation / downregulation of 23/63, 41/39 and 79/79 proteins and of 127/112, 52/47 and 105/226 phosphorylation sites in 85/92, 45/36 and 79/146 phosphoproteins, respectively. Bioinformatic analyses revealed that Cdc14 could participate in many biological and cellular processes, such as carbohydrate metabolism, glycerophospholipid metabolism, the MAP Kinase signaling pathway, and DNA conformation, by regulating protein expression and key kinase phosphorylation in response to different environmental cues. These indicate that in B. bassiana, Cdc14 is a vital regulator of not only protein expression but also many phosphorylation events involved in developmental and stress-responsive pathways. Fourteen conserved and novel motifs were identified in the fungal phosphorylation events.

The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology. Genetic analysis of 115 variants in common genes related to HL, GJB2, SLC26A4 and MT-RNR, was performed on 695 subjects with non-syndromic hearing loss (NSHL) from the Northern China. The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MT-RNR1 variants. The variant allele frequency of GJB2, SLC26A4 and MT-RNR1 was 19.8% (275/1390), 21.9% (304/1390), and 0.86% (6/695), respectively. This approach can explain ~40% of NSHL cases and thus is a useful tool for establishing primary molecular diagnosis of NSHL in clinical genetics.

Currently, the standard treatment for newly diagnosed glioblastoma multiforme (GBM) is maximal safe surgical resection followed by radiation therapy with concurrent and adjuvant temozolomide. However, disease recurs in almost all patients, and the optimal salvage treatment for recurrent GBM remains unclear. We conducted a systematic review and meta-analysis of published clinical trials to assess the efficacy and toxicities of angiogenesis inhibitors alone as salvage treatment in these patients.Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). Demographic data, treatment regimens, objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), 6-months PFS rate, 1-year OS and grade 3/4 toxicities were extracted. We also compared the main outcomes of interest between bevacizumab and other angiogenesis inhibitors. All analyses were performed using Comprehensive Meta Analysis software (Version 2.0).A total of 842 patients were included for analysis: 343 patients were treated with bevacizumab, 386 with other angiogenesis inhibitors and 81 with thalidomide. The pooled ORR, 6-months PFS, and 1-year OS for recurrent GBM patients receiving angiogenesis inhibitors was 20.1%, 19.5% and 29.3%, respectively. The use of single agent bevacizumab in recurrent GBM significantly improved ORR and 6-months PFS when compared to other angiogenesis inhibitors [relative risk (RR) 2.93, 95% CI 1.38-6.21; p = 0.025; and RR 2.36 95% CI 1.46-3.82; p

BACKGROUND:Malnutrition and anemia affect large numbers of young children living in poor areas of China. Multi-micronutrient deficiencies may be related to the prevalence of anemia in different populations, and identifying the risk factors that render children susceptible to anemia is the first step in combating anemia effectively. METHODS:In this cross-sectional study, a total of 1370 children under 3 years old were selected based on probability proportional to size sampling principles from poor counties of China. Basic characteristics data were collected by questionnaire; then anthropometrics and hemoglobin were measured in the field and anemia prevalence evaluated. Venous blood was drawn from children aged 12-35 months (N = 553) to evaluate micronutrient status. Logistic regression was used to identify the risk factors for children's anemia. RESULTS:Among children aged 0-35 months, the prevalence of stunting, low body weight and wasting was 17.5%, 8.6% and 5.1%, respectively, and 25.6% of the children were affected by anemia, with more anemic infants and younger children than older children (P

BackgroundSeveral studies have assessed the effects of computer-based cognitive programs (CCP) in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults.MethodsSix electronic databases (through October 2014) were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD) and 95% confidence intervals (CI) of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index.ResultsTwelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001) and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007) but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27). Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01).ConclusionCCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings.

Association between hyperuricaemia and chronic kidney disease has been studied widely, but the influence of uric acid on the kidneys remains controversial. We aimed to summarize the association between uric acid and diabetic kidney disease (DKD), and to evaluate the role of uric acid in DKD.We enrolled 3,212 type 2 diabetic patients in a cross-sectional study. The patients' basic characteristics (sex, age, BMI, duration of disease, and blood pressure) and chemical parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), microalbuminuria, creatinine, and uric acid) were recorded, and the association between uric acid and DKD was evaluated.In the 3,212 diabetic patients, the prevalence of diabetic kidney disease was higher in hyperuricaemic patients than in patients with normouricaemia (68.3% vs 41.5%). The prevalence of DKD increased with increasing uric acid (p < 0.0001). Logistic analysis identified uric acid as an independent predictor of DKD (p < 0.0001; adjusted OR (95%CI) = 1.005 (1.004-1.007), p < 0.0001). Uric acid was positively correlated with albuminuria and creatinine levels (p < 0.0001) but negatively correlated with eGFR (p < 0.0001) after adjusting for confounding factors.Hyperuricaemia is a risk factor for DKD. Serum uric acid levels within the high-normal range are independently associated with DKD.

Inter-specific hybridization occurs frequently in higher plants, and represents a driving force of evolution and speciation. Inter-specific hybridization often induces genetic and epigenetic instabilities in the resultant homoploid hybrids or allopolyploids, a phenomenon known as genome shock. Although genetic and epigenetic consequences of hybridizations between rice subspecies (e.g., japonica and indica) and closely related species sharing the same AA genome have been extensively investigated, those of inter-specific hybridizations between more remote species with different genomes in the rice genus, Oryza, remain largely unknown.We investigated the immediate chromosomal and molecular genetic/epigenetic instability of three triploid F1 hybrids produced by inter-specific crossing between species with divergent genomes of Oryza by genomic in situ hybridization (GISH) and molecular marker analysis. Transcriptional and transpositional activity of several transposable elements (TEs) and methylation stability of their flanking regions were also assessed. We made the following principle findings: (i) all three triploid hybrids are stable in both chromosome number and gross structure; (ii) stochastic changes in both DNA sequence and methylation occurred in individual plants of all three triploid hybrids, but in general methylation changes occurred at lower frequencies than genetic changes; (iii) alteration in DNA methylation occurred to a greater extent in genomic loci flanking potentially active TEs than in randomly sampled loci; (iv) transcriptional activation of several TEs commonly occurred in all three hybrids but transpositional events were detected in a genetic context-dependent manner.Artificially constructed inter-specific hybrids of remotely related species with divergent genomes in genus Oryza are chromosomally stable but show immediate and highly stochastic genetic and epigenetic instabilities at the molecular level. These novel hybrids might provide a rich resource of genetic and epigenetic diversities for potential utilization in rice genetic improvements.

Mammary gland development is controlled by several genes. Although miRNAs have been implicated in mammary gland function, the mechanism by which miR-486 regulates mammary gland development and lactation remains unclear. We investigated miR-486 expression in cow mammary gland using qRT-PCR and ISH and show that miR-486 expression was higher during the high-quality lactation period. We found that miR-486 targets phosphoinositide signaling in the cow mammary gland by directly downregulating PTEN gene expression and by altering the expression of downstream genes that are important for the function of the mammary gland, such as AKT, mTOR. We analyzed the effect of β-casein, lactose and triglyceride secretion in bovine mammary gland epithelial cells (BMECs) transfected by an inhibitor and by mimics of miR-486. Our results identify miR-486 as a downstream regulator of PTEN that is required for the development of the cow mammary gland.

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).

The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction).1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety.From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127).In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy.ClinicalTrials.gov NCT02486354.

Previous studies showed that autoantibodies (M2-AA) against the second extracellular loop of M2 muscarinic receptor (M2AChR-el2) from dilated cardiomyopathy (DCM) serum could induce DCM-like morphological changes in mice hearts. However, the effects of M2-AA on the cardiac function during the process of DCM and the potential mechanisms are not fully known. The present study was designed to dynamically observe the cardiac function, mitochondrial changes, and M2 receptor binding characteristics in rats long-term stimulated with M2-AA in vivo.M2-AA-positive model was established by actively immunizing healthy male Wistar rats with synthetic M2AChR-el2 peptide for 18 months. Meanwhile, vehicle group rats were administrated with physiological saline. The change of mitochondrial membrane potential (ΔΨm) was detected by radionuclide imaging. The ultrastructure of mitochondria was observed under electron microscopy. The M2 receptor binding characteristics were determined by radioactive ligand binding assay.After immunization for 12 months, compared with vehicle group, M2AChR-el2-immunized rats showed decreased myocardial contractility and cardiac diastolic function evidenced by declined maximal rate of rise of ventricular pressure and increased left ventricular end-diastolic pressure, respectively. Additionally, mitochondrial swelling and vacuolation were observed. At 18 months, M2AChR-el2-immunized rats manifested significant decreased cardiac systolic and diastolic function and pathological changes such as enlargement of right ventricular cavity and wall thinning; and the mitochondrial damage was aggravated. Furthermore, the M2 receptor maximum binding capacity (Bmax) of the M2AChR-el2-immunized rats significantly decreased, while the M2 receptor dissociation constant (Kd) was increased.Our study suggested that long-term stimulation with M2-AA leaded to the ventricular dilatation and gradual deterioration of cardiac dysfunction. Mitochondrial damage and the down-regulation of M2 receptor density and affinity may be involved in the process.

BackgroundHouttuynia cordata Thunb. is an important traditional medical herb in China and other Asian countries, with high medicinal and economic value. However, a lack of available genomic information has become a limitation for research on this species. Thus, we carried out high-throughput transcriptomic sequencing of H. cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development.Principal findingsIllumina paired-end sequencing technology produced over 56 million sequencing reads from H. cordata mRNA. Subsequent de novo assembly yielded 63,954 unigenes, 39,982 (62.52%) and 26,122 (40.84%) of which had significant similarity to proteins in the NCBI nonredundant protein and Swiss-Prot databases (E-value ConclusionsThis is the first application of Illumina paired-end sequencing technology to investigate the whole transcriptome of H. cordata and to assemble RNA-seq reads without a reference genome. These data should help researchers investigating the evolution and biological processes of this species. The SSR markers developed can be used for construction of high-resolution genetic linkage maps and for gene-based association analyses in H. cordata. This work will enable future functional genomic research and research into the distinctive active constituents of this genus.