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Fructose intolerance in mammals is caused by defects in fructose absorption and metabolism. Fructose-1,6-bisphosphatase 1 (FBP1) is a key enzyme in gluconeogenesis, and its deficiency results in hypoglycemia as well as intolerance to fructose. However, the mechanism about fructose intolerance caused by FBP1 deficiency has not been fully elucidated. Here, we demonstrate that hepatic but not intestinal FBP1 is required for fructose metabolism and tolerance. We generated inducible knockout mouse models specifically lacking FBP1 in adult intestine or liver. Intestine-specific deletion of Fbp1 in adult mice does not compromise fructose tolerance, as evidenced by no significant body weight loss, food intake reduction, or morphological changes of the small intestine during 4 weeks of exposure to a high-fructose diet. By contrast, liver-specific deletion of Fbp1 in adult mice leads to fructose intolerance, as manifested by substantial weight loss, hepatomegaly, and liver injury after exposure to a high-fructose diet. Notably, the fructose metabolite fructose-1-phosphate is accumulated in FBP1-deficient liver after fructose challenge, which indicates a defect of fructolysis, probably due to competitive inhibition by fructose-1,6-bisphosphate and may account for the fructose intolerance. In conclusion, these data have clarified the essential role of hepatic but not intestinal FBP1 in fructose metabolism and tolerance.

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral non-sensory region. Here we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear non-sensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane, a flattened spiral prominence, and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the non-sensory epithelium covering the outer border Claudius cells, outer sulcus root cells and spiral prominence epithelial cells. Transcriptome analysis shows ZBTB20 regulates genes coding for tectorial membrane proteins in the greater epithelial ridge, and those preferentially expressed in root cells and spiral prominence epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral non-sensory domain.

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.

Yimeng Geng,1,* Yeling Mei,1,* Ying Xi,2 Junlin Yu,1 Ke Meng,1 Tengfei Zhang,1 Wang Ma1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Radiotherapy, Puyang Oilfield General Hospital, Puyang, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wang Ma; Tengfei Zhang Email doctormw@zzu.edu.cn; zhangtengfei84@163.comBackground and Objectives: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation demonstrate only a median progression-free survival (PFS) of 8 to 10 months and undergo EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy. For decades, bilirubin has been reported to be associated with the onset and prognosis of lung cancer as a prooxidant. This study aimed to investigate the prediction of pretreatment circulating bilirubin for PFS in lung adenocarcinoma (LAC) patients who underwent EGFR-TKIs targeted therapy.Patients and Methods: LAC cases diagnosed and undergone EGFR-TKIs targeted therapy at The First Affiliated Hospital of Zhengzhou University between 2013 and 2015 were retrospectively reviewed. A total of 180 patients were studied according to inclusion and exclusion criteria. Follow-up data were collected for all patients until the disease progressed.Results: Univariate analysis showed that the levels of pretreatment total bilirubin (TBIL), indirect bilirubin (IBIL) and direct bilirubin (DBIL) were related to PFS (all p< 0.05). Considering the close relationship among the three factors, we combined TBIL, IBIL and DBIL into one total factor, which is called bilirubin. Kaplan–Meier survival curves and Log rank tests indicated that patients with lower bilirubin levels had a shorter median PFS than those with higher bilirubin levels (8 vs. 15 months; p= 0.002). Multivariate analysis demonstrated that pretreatment bilirubin is an independent prognostic factor (HR=0.454, CI: 0.267– 0.773, p= 0.004).Conclusion: This study confirms that bilirubin can predict the prognosis of LAC patients who had undergone EGFR-TKIs targeted therapy.Keywords: bilirubin, lung adenocarcinoma, EGFR-TKIs, progression-free survival, prognosis

Additional file 1. Additional figures and table.

The transposon-associated CRISPR-Cas system is emerging as a powerful tool for targeted genetic manipulation. Using this system, targeted genomic knockins and knockouts can be achieved, independently of the host-cell repair machinery, thereby significantly improving our ability to perform genome editing in a wider variety of cell types.

Additional file 1: Table S1. The urinary nitrate level of various cardiovascular diseases.

To study the effects of an axial magnetic field on the discharge characteristics of Ar inductively coupled plasma, a set of discharge plasma generators was designed. The plasma parameters such as electron temperature and electron density were diagnosed with a Langmuir probe. The research showed that as the air pressure was 10 Pa, with the increase in axial magnetic field intensity, the electron temperature and electron density reduced continuously in the central discharge region, while the threshold power of discharge mode transition increased constantly. The analysis suggested that due to the circumnutation of charged particles acted upon by Lorentz force, the introduction of the axial magnetic field had a constraint effect on the particle movement and energy transfer and decreased the collision between the high-energy electron in the discharge sheath and the electron in the central region, thereby reducing the electron density and inductive coupling efficiency. From further analysis of the electron energy probability function, it could be found that in the E mode, the constraint effect of the axial magnetic field on electron motion was more obvious. The proportion of the high-energy electron (>27 eV) was apparently higher than that in the H mode, and the electron energy distribution was more even. This was caused by less electron collision.

Dot is the smallest structural unit of image printing. Micro-characteristic of each printing dot such as spreading area, dot shape and three-dimensional shape which are formed on the surface of substrates affect the image replication quality directly. It is significant to accurately extract and analyze dot microstructure in the process of image transfer for evaluating the quality of image replication .Different shapes of printing dots from the standard offset proof are extracted through microscopic test system. The optimal threshold segmentation algorithm was determined by experiment which gets accurate microscopic quantitative value of the dot, the obtained two-dimensional and three-dimensional shape of printing dot became the basis to evaluate the quality of image replication. The between-cluster variance method is used for dot image segmentation. The research was carried on to track image edge after image threshold and to extract the characteristic parameters to accurately characterize the two-dimensional shape, thus characterizing the image replication quality of dot plane form accordingly; on the basis of collected dot two-dimensional data, the experiment was conducted to combine with gray value differences of single dot caused from ink accumulation within its shape areas. Besides, dot density contour and three-dimensional data were quantized by programming in order to restore three-dimensional shape of printing dot on the surface of substrates quantitatively and intuitively. It shows that quality of dot micro-morphology is the fundamental guarantee of image replication quality. The changes of dot shape, area as well as three-dimensional shape in the process of image replication affect the printing quality. Extraction and analysis dot microstructure can detect dot replication quality intuitively which becomes new method to evaluate image replication quality.

Objective: Blurred images in full-field digital mammography are a problem in the UK Breast Screening Programme. Technical recalls may be due to blurring not being seen on lower resolution monitors used for review. This study assesses the visual detection of blurring on a 2.3-MP monitor and a 5-MP report grade monitor and proposes an observer standard for the visual detection of blurring on a 5-MP reporting grade monitor. Methods: 28 observers assessed 120 images for blurring; 20 images had no blurring present, whereas 100 images had blurring imposed through mathematical simulation at 0.2, 0.4, 0.6, 0.8 and 1.0mm levels of motion. Technical recall rate for both monitors and angular size at each level of motion were calculated. χ2 tests were used to test whether significant differences in blurring detection existed between 2.3- and 5-MP monitors. Results: The technical recall rate for 2.3- and 5-MP monitors are 20.3% and 9.1%, respectively. The angular size for 0.2- to 1-mm motion varied from 55 to 275 arc s. The minimum amount of motion for visual detection of blurring in this study is 0.4mm. For 0.2-mm simulated motion, there was no significant difference [χ2 (1, N=1095)51.61, p=0.20] in blurring detection between the 2.3- and 5-MP monitors. Conclusion: According to this study, monitors ≤2.3MP are not suitable for technical review of full-field digital mammography images for the detection of blur. Advances in knowledge: This research proposes the first observer standard for the visual detection of blurring. published

Dot gain divides into physical and optical dot gain. These two parts constitute the comprehensive dot gain in the process of printing. Ink spreading on the surface of paper is used for the analysis of physical dot gain and light scattering function model is used for optical dot gain. Trace the dots on the CTP plate and offset printing proof to analyze the influence of image micro-parameters caused by dot gain. Physical and optical dot gain are quantized to research the correlation between dot gain and shape of dot. It shows that: optical dot gain of AM dot accounts for a larger proportion; dot gain of all types has no relation with shape of dot. Besides, physical dot gain of FM dot accounts for a larger proportion than optical dot gain.

The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratory-confirmed cases. In this study, we estimated the number of the actual H7N9 cases in Jiangsu, China using a probabilistic multiplier model. Then, disability adjusted life years (DALYs), direct and indirect economic loss caused by this disease were calculated and analyzed. Till September 2017, the estimated total number of H7N9 cases was 2 952 [median, 90% probability range (PR): 1 487−22 094], which was 11.8 times (5.9−88.4) as large as the reported number. The median morbidity was estimated to be 4 (90% PR: 2−29) per 100 000 population. The total DALYs loss was 16 548 years, and the total economic loss (direct and indirect) was estimated to be RMB 1 044 618 758 (US$ 16.7 M). The average economic loss for per case and for per year was RMB 353 868 (US$ 56 440) and RMB 232 137 502 (US$ 37.0 M), respectively. The actual burden of human H7N9 infections was much heavier than what was documented. Our study provided an approach to estimate actual burden of infectious diseases using laboratory-confirmation.

Kinetic behaviors of fluorine leaching from tea were studied. The leaching process of fluorine could be divided into initial fast stage and later slow stage. The duration of fast stage 1 depended on leaf particle size and temperature. The higher the temperature and the smaller the leaf particle size, the shorter the duration of initial fast stage. Based on the test results, a two-step infusion method was developed to control fluorine level in tea liquor. When the tea was infused in 50°C water for 20 s (first infusion) and then the residue leaf was re-infused in boiling water for 5 min (second infusion), more than 26% of total fluorine was removed during first infusion, but more than 80% of catechins and caffeine of the teas remained in the second infusions which had a F level 0.70 mg L-1 or less. It reflected that the two-step infusion method is an alternative to control excessive fluorine exposure for tea drinkers. Key words: Green tea, fluorine, kinetics, diffusion coefficients, two-step infusion.

Adenovirus serotype 3 and 7 outbreaks have occurred periodically in northern, eastern, and southern China since 1955, but there has been no report since the adenovirus serotype 7 outbreak first occurred in Hangzhou, China, in 1991. Here we explored the epidemiology and etiology of two adenovirus serotype 3 outbreaks in Hangzhou in 2011. One acute respiratory outbreak was found in Chun'an County, where a total of 371 cases were confirmed in 5 of 23 towns from 4 to 31 May 2011. The outbreak affected 18.57% (13/70) of schools and 14.49% (90/621) of classes. The incidence was 5.18% (371/7,163). The population was distributed among individuals ages 7 to 15 years. No parents or teachers were infected. Another pharyngoconjunctival fever outbreak was discovered in the Chenjinglun Swimming Center located in the Xihu District between 1 and 15 July 2011. A total of 134 cases were confirmed in 900 amateur swimmers, with an incidence of 14.89% (134/900). The ages ranged from 4 to 9 years. The two outbreaks had no severe complications or death. The viruses in 66.67% (10/15) of throat swabs from children with acute respiratory infections and 100% (10/10) of the swabs from children with pharyngoconjunctival fever were confirmed to be adenovirus serotype 3 with 100% homology by PCR. Of these samples, 60.0% (12/20) had a classical characteristic cytopathic effect, presented as grape-like clusters at 72 h after infection in HEp-2 cells. In conclusion, the acute respiratory infection and pharyngoconjunctival fever outbreak in Hangzhou were caused by the completely homologous type 3 adenovirus in subgenus B. Moreover, these outbreaks demonstrated rapid transmission rates, possibly due to close contact and droplet transmission.

Silicon facet formation during directional solidification is simulated by cellular automaton (CA) modeling in which anisotropic interfacial energy and kinetics are considered. Numerical simulations were performed with different anisotropy strengths of interfacial energy and they show good agreement with analytical equilibrium shapes obtained by the Gibbs-Thomson equation. We also compare our results of anisotropic kinetics with in situ observation experiments and the results of the phase model to verify the accuracy of our model. Simulation results of facet formation show that perturbation is promoted to the corner by the negative temperature gradient of the interface and the heat accumulation location leads to the disappearance of small corners.

To understand the status and epidemic rules of human important parasite infections, and evaluate the control effect in Xihu District, so as to provide evidence for improving future parasitic disease control.Two surveys were performed in 2003 and 2009 in accordance with The Regulations of National Survey of the Distribution of Human Parasites, respectively.Four kinds of parasites were identified in 2003. The total infection rate was 7.81%, and the infection rates of hookworm, Ascaris lumbricoides, Trichuris trichiura, and Enterobius vermicularis were 5.61%, 0.13%, 1.83% and 4.43%, respectively. In 2009, the total rate was 2.07% and the infection rate of hookworm was 1.87%, while the infection rates of Ascaris lumbricoides, Trichuris trichiura and Enterobius vermicularis were all 0.10%. The high-risk groups were the low age group and middle-aged group.The total infection rate of human parasites and each parasite infection rate in Xihu District have declined significantly, and hookworm is the main kind of human parasite in the district.