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DnaJs are the common molecular chaperone proteins with strong structural and functional diversity. In recent years, only several DnaJ family members have been found to be able to regulate leaf color, and it remains to be explored whether there are other potential members that also regulate this character. Here, we identified 88 putative DnaJ proteins from Catalpa bungei, and classified them into four types according to their domain. Gene-structure analysis revealed that each member of CbuDnaJ family had same or similar exon-intron structure. Chromosome mapping and collinearity analysis showed that tandem and fragment duplication occurred in the process of evolution. Promoter analyses suggested that CbuDnaJs might be involved in a variety of biological processes. The expression levels of DnaJ family members in different color leaves of Maiyuanjinqiu were respectively extracted from the differential transcriptome. Among these, CbuDnaJ49 was the largest differentially expressed gene between the green and yellow sectors. Ectopic overexpression of CbuDnaJ49 in tobacco showed that the positive transgenic seedlings exhibited albino leaves, and the contents of chlorophyll and carotenoid were significantly reduced compared with those of wild type. The results suggested that CbuDnaJ49 played an important role in regulating leaf color. This study not only identified a novel gene of DnaJ family members regulating leaf color, but also provided new germplasm for landscaping.

Purpose: To analyze the clinical data and prognosis of patients with World Health Organization (WHO) functional class I pulmonary arterial hypertension (PAH). Methods: This research retrospectively analyzed the clinical data (baseline, laboratory as well as echocardiography and right heart catheterization data) of 63 class I PAH patients diagnosed and treated in the Department of Cardiology, First Affiliated Hospital of Zhengzhou University, between January 2021 and June 2022. The mean follow-up time was 10.7±6.5 months. The treatment and prognosis of the patients were analyzed. Results: Among the class I PAH patients, the average age at diagnosis was 39.7±12.7 years, with females accounting for 92.1%; 44.4% of patients were at grade III or IV; 55.6% were at medium-high risk. In the subgroup analysis, there were more cases with grade III/IV cardiac function (P=0.03) and high risk in idiopathic PAH (IPAH) group than those in congenital heart disease-associated (CHD-PAH) and connective tissue disease-associated PAH (CTD-PAH) groups (P=0.04). CHD-PAH patients tended to present with higher pulmonary systolic blood pressure, mean pulmonary artery pressure and pulmonary vascular resistance than CTD-PAH patients (P

ObjectiveTo use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia.MethodsTwelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators. Results(1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P <0.05).ConclusionJTTZR may interfere in patients with obese T2DM with dyslipidemia by regulating pathways such as fatty acid degradation, glycolysis/gluconeogenesis, and pyruvate metabolism.

Natural product-originated carbon dots represent a charming and valuable platform for bio-fluorescence probes; however, the application scope of these probes is seriously restricted, due to the indistinct molecular structures of these bio-probes and the inaccurate interactions between the probe and detected guest molecule. Herein, a novel strategy of keto–enol tautomerism-mediated quinone aromatization has been achieved for Cochineal bio-based quinone carbon dot synthesis. Then, a photo-induced intermolecular cross-redox reaction was accomplished with tetracycline for quinone carbon dot molecule transformation and fluorescence change. This work represents a pioneer for intermolecular interaction simulation and bonding energy evaluation of carbon dots for trace organics detection.

Additional file 1. The supplementary figures and tables of this article.

Pulmonary fibrosis (PF) is the end stage of various chronic and progressive interstitial lung diseases. TGF-β, a profibrotic cytokine, can promote epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and fibroblast proliferation, which contribute to progressive lung remodeling in PF. The Wenfei Buqi Tongluo (WBT) formula has been certified to be effective in the prevention and treatment of PF in clinical practice and has inhibitory effects on EMT, inflammation, and profibrotic factors. However, the pharmacological mechanisms of WBT against PF need to be further explored. In this study, we first analyzed the chemical components of the WBT formula using the UHPLC/Q-TOF-MS analysis. The potential targets of the identified compounds from WBT were predicted by the network pharmacology, which was confirmed by in vivo and in vitro study. After screening by the PubChem database, we first identified the 36 compounds of WBT and predicted the TGF-β signaling pathway, with ECM degradation as potential mechanism of WBT against PF by the network pharmacology. Furthermore, WBT treatment inhibited the levels of TGF-β and Smad3 phosphorylation and subsequently alleviated EMT and ECM accumulation in the bleomycin-induced mouse model and TGF-β1–induced cell model. These findings indicate that WBT can block the progressive process of PF by inhibiting EMT and promoting ECM degradation via the TGF-β/Smad3 pathway. This study may provide new insights into the molecular mechanism of WBT for the prevention and treatment of PF in the clinical application.

Background. Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and HE in cirrhotic patients. Methods. We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results. Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73-11.32, P=0.002). The heterogeneity was moderate (I2=66%), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions. Our meta-analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.

Background Rice rooting ability is a complex agronomical trait that displays heterosis and plays an important role in rice growth and production. Only a few quantitative trait loci (QTLs) have been identified by bi-parental population. More genes or QTLs are required to dissect the genetic architecture of rice rooting ability. Results To characterize the genetic basis for rice rooting ability, we used a natural rice population, genotyped by a 90 K single nucleotide polymorphism (SNP) array, to identify the loci associated with rooting-related traits through the genome-wide association study (GWAS). Population structure analysis divided the natural population into two subgroups: indica and japonica. We measured four traits for evaluating rice rooting ability, namely root growth ability (RGA), maximum root length (MRL), root length (RL), and root number (RN). Using the association study in three panels consisting of one for the full population, one for indica, and one for japonica, 24 SNPs associated with rooting ability-related traits were identified. Through comparison of the relative expression levels and DNA sequences between germplasm with extreme phenotypes, results showed that LOC_Os05g11810 had non-synonymous variations at the coding region, which may cause differences in root number, and that the expression levels of LOC_Os04g09900 and LOC_Os04g10060 are closely associated with root length variation. Conclusions Through evaluation of the rice rooting ability-related traits and the association mapping, we provided useful information for understanding the genetic basis of rice rooting ability and also identified some candidate genes and molecular markers for rice root breeding.

Sugarcane, the main sugar crop harvested around the world, is sensitive to cold stress. miRNA plays an important role in plant response to abiotic stress. In order to discover the miRNAs that play a continuing role in sugarcane response to cold stress in a later period (2 d), four sugarcane small RNA libraries were constructed. In this study, a total of 144 miRNAs were identified. Among them, 32 miRNAs showed differential expression in two relatively cold tolerant and sensitive sugarcane cultivars (FN39 and ROC22). The expression tendency for ten randomly selected differentially expressed miRNAs and their predicted targets by qRT-PCR were consistent with those from sequencing data. To further investigate the miRNA role, ScmiR393 in sugarcane was selected and overexpressed in Arabidopsis. After a relatively long cold treatment, the over-expressed ScmiR393 Arabidopsis showed better growth than the wild type, and this phenomenon was supported by the higher anthocyanin and proline contents, lower MDA and H2O2 contents, and higher SOD, POD and CAT activities, as well as the induction of some cold resistant genes including CBFs. In addition, transcriptome analysis revealed that the overexpression of ScmiR393 inhibited the auxin signaling pathway by targeting TIR1, and this may also lead to ethylene signaling inhibition. Inhibited ethylene signaling may induce the cold-resistant genes and promote anthocyanin accumulation and bolting, eventually, the cold tolerance of Arabidopsis may be improved. This study contributes to the present sugarcane miRNA resource and shows an important role of ScmiR393 in plant response to cold stress.

Additional file 1: Table S1. Diagnoses and the used diagnostic methods for the three broad ARF etiologies. Table S2. Comparison of ARF group and control group.

Red seaweeds are reported to represent the largest group of algae, with more species accounted for than the combination of brown and green seaweeds. Due to the high amount of polysaccharides in red seaweeds, they are mainly utilized for commercial agar and carrageenan production in industry. However, increasing studies indicate other valuable compounds such as lipids and polyphenols could be potential utilized for multiple human needs (e.g., drug development) (1, 2). With increasing studies demonstrating the potential health benefits of seaweed components, two red seaweed species commonly consumed in Asia, hong qı´ lı´n c a`i (HQL), Eucheuma sp and zhe` gu¯ ca`i (ZGC), Caloglossa leprieurii, were investigated on to determine the anti-inflammatory effects of their extractable lipophilic bioactives (ELB) and bound lipophilic bioactives (BLB) in lipopolysaccharide( LPS)-treated RAW 264.7 macrophages. The chemical composition of ELB and BLB was characterized in terms of total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC), oxygen radical absorbance capacity (ORAC), and etc. Six phenolic compounds were identified in ZGC extracts and one was detected in HQL. All extracts inhibited the nitric oxide (NO) production in LPS-induced macrophages, which was associated with downregulation of iNOS and COX-2 protein expression and up-regulation of HQ-1 and NQO1 protein expression. Overall, our results showed that both ELB and BLB in HQL and ZGC seaweeds presented potential anti-inflammatory activities. These results warrant future investigations to determine the mode of actions of red seaweed bioactives and their efficacy in humans.

Background: Schistosomiasis is an immunopathogenic disease in which Th17 cells play vital roles. Hepatic granuloma formation and subsequent fibrosis are its main pathologic manifestations and the leading causes of hepatic cirrhosis, and effective therapeutic interventions are lacking. In this study, we explored the effects of fasudil, a selective RhoA&ndash, Rho-associated kinase (ROCK) inhibitor, on Th17 cells and the pathogenesis of schistosomiasis. Methods: Mice were infected with Schistosoma japonicum and treated with fasudil. The worm burden, hepatic granuloma formation, and fibrosis were evaluated. The roles of fasudil on Th17, Treg, and hepatic stellate cells were analyzed. Results: Fasudil therapy markedly reduced the granuloma size and collagen deposit in livers from mice infected with S. japonicum. However, fasudil therapy did not affect the worm burden in infected mice. The underlying cellular and molecular mechanisms were investigated. Fasudil suppressed the activation and induced the apoptosis of CD4+ T cells. Fasudil inhibited the differentiation and effector cytokine secretion of Th17 cells, whereas it upregulated Treg cells in vitro. It also restrained the in vivo interleukin (IL)-4 and IL-17 levels in infected mice. Fasudil directly induced the apoptosis of hepatic stellate cells and downregulated the expressions of hepatic fibrogenic genes, such as collagen type I (Col-I), Col-III, and transforming growth factor-1 (TGF-&beta, 1). These effects may contribute to its anti-pathogenic roles in schistosomiasis. Conclusions: Fasudil inhibits hepatic granuloma formation and fibrosis with downregulation of Th17 cells. Fasudil might serve as a novel therapeutic agent for hepatic fibrosis due to schistosome infections and perhaps other disorders.

In this study, alcoholysis of phosphatidylcholine (PC) catalyzed by two lipases (Novozym 435 and Lipozyme RM IM) was performed in n-hexane to evaluate the effects of mono-, di-, and trihydric alcohols (ethanol, 1-butanol, 1,2-ethanediol, 1,2-propanediol, and glycerol) on the alcoholysis reactions. In the reactions, as PC was converted into lysophosphatidylcholine (LPC), LPC was simultaneously alcoholyzed and converted into glycerophosphorylcholine (GPC). The alcohols affected the alcoholysis of both PC and LPC. When alcoholysis was catalyzed by Novozym 435, the reaction efficiencies of the selected alcohols in the alcoholysis of PC followed the order 1,2-propanediol ≈ ethylene glycol> 1-butanol > ethanol > glycerol, and the reaction efficiencies of these alcohols in the alcoholysis of LPC were 1,2-propanediol > ethylene glycol> 1-butanol ≈ glycerol > ethanol. For alcoholysis catalyzed by Lipozyme RM IM, the reaction efficiencies of alcohols in alcoholysis of PC followed the order ethylene glycol ≈1,2-propanediol > glycerol > ethanol > 1-butanol, and the reaction efficiencies in the alcoholysis of LPC were ethylene glycol > glycerol > 1,2-propanediol > ethanol > 1-butanol. In general, in the lipase-catalyzed alcoholysis of PC, reaction efficiencies with dihydric alcohols are higher than those with mono- and trihydric alcohols.Supported by National Natural Science Foundation of China (No. 31772003), and Basic Research Funds in Henan University of Technology (No. 2017RCJH07). Keywords:: Alcoholysis, Phosphatidylcholine, Lipase, Alcohols

Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness.

Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium (IKr) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of IKr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na2S2O4) in ventricular myocytes of guinea pigs. The IKr current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of IKr is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100μmol/L). The value of IKr tail current density increased from 0.516±0.040 pA/pF in I/R to 0.939±0.091 pA/pF when treated with vitamin E. Moreover, we also demonstrated that QTc interval was increased by I/R and reversed by Vitamin E in isolated guinea pig hearts. In conclusion, the inhibition of IKr is one of the underlying mechanisms of prolongation of QT interval and APD in I/R. Vitamin E might have a benefit in coronary reperfusion therapy.

Human homolog of mouse double minute 2 (HDM2) is an oncogene frequently overexpressed in cancers with poor prognosis, but mechanisms of controlling its abundance remain elusive. In an unbiased biochemical search, we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. In human breast cancer cells, FBXO22 knockdown (KD) increased cell invasiveness, which was driven by elevated levels of HDM2. Moreover, mouse 4T1 breast tumor model studies revealed that FBXO22 KD led to a significant increase of breast tumor cell metastasis to the lung. Finally, low FBXO22 expression is correlated with worse survival and high HDM2 expression in human breast cancer. Altogether, these findings suggest that SCFFBXO22 targets HDM2 for degradation and possesses inhibitory effects against breast cancer tumor cell invasion and metastasis.

Metabolic syndrome (MS), which includes metabolic disorders such as protein disorder, glucose disorder, lipid disorder, and carbohydrate disorder, has been growing rapidly around the world. Glycolipid disorders are a main type of metabolic syndrome and are characterized by abdominal obesity and abnormal metabolic disorders of lipid, glucose, and carbohydrate utilization, which can cause cardiovascular and cerebrovascular diseases. Glycolipid disorders are closely related to intestinal flora and its metabolites. However, studies about the biological mechanisms of the intestinal flora and its metabolites with glycolipid disorders have not been clear. When glycolipid disorders are treated with drugs, a challenging problem is side effects. Traditional Chinese medicine (TCM) and dietary supplements have fewer side effects to treat it. Numerous basic and clinical studies have confirmed that TCM decoctions, Chinese medicine monomers, or compounds can treat glycolipid disorders and reduce the incidence of cardiovascular disease. In this study, we reviewed the relationship between the intestinal flora and its metabolites in glycolipid metabolic disorders and the effect of TCM in treating glycolipid metabolic disorders through the intestinal flora and its metabolites. This review provides new perspectives and strategies for future glycolipid disorders research and treatment.

A new two-dimensional modeling approach combining the cellular automaton(CA) and the lattice Boltzmann model(LBM) was developed to simulate heat transport, fluid flow, solute diffusion, and dendritic growth in the process of the Al-4.7%Cu solidification of the single-phase solid solution alloy. And the changes of dendritic morphology and constituent under convection were analyzed. The present model improved the solutal distribution approach at the solid-liquid (S/L) interface, which made the change of solute more consistent with the actual transport. The simulation results demonstrate that dendritic morphology is strongly influenced by forced convection, comparing with that without accounting for convection. Under the forced convection, the dendrite grain sizes tend to be similar; the constituent in the interdendritic region is more homogeneous; and the composition in the whole solidification region exhibits a certain gradient trend from upstream to downstream.

Stem borer incidences in sugarcane result in huge economic losses to sugarcane cultivation worldwide. Genetically modified (GM) sugarcane with stem borer resistance has good prospects for commercialization due to its reduced use of pesticides and increased yield of cane and sugar. The dynamic research evaluation for management system has been used to estimate the economic impact of the commercialization of GM sugarcane in Guangxi and Yunnan provinces of China. The results indicated that GM sugarcane has the potential to increase the cane productivity and reduce the use of pesticides, resulting in economic benefits for the producers as well as the consumers of sugarcane in China, and economic surplus of GM sugarcane in Guangxi and Yunnan has been estimated around 1052.91 and 3413.48 million RMB, respectively, accounting for 23.57 and 76.43 % of the total benefits. It is indicated that the commercialization of stem borer-resistant GM sugarcane has more potential in Yunnan due to the higher use of pesticides in the province. While providing the evidence for high economic impact of GM sugarcane, the study could also help policy makers, farmers and consumers for effective decision-making.

Based on the 2000-2018 data of China’s direct investment in U.S. tourism industry, this paper used the random effect models to quantitatively measure the driving mechanism of Chinese direct investment in U.S. tourism industry. The results showed that: China’s direct investment in U.S. tourism is mainly influenced by the four driving forces of economic development, tourism development, cultural affinity, investment environment and system. “Cultural affinity” is the characteristic of the U. S. which is different from the FDI of Chinese tourism in the global perspective.

BACKGROUD: HyperCVAD is one of the most frequent used protocols in adult ALL in routine practice. On the other hand, the CALLG2008 protocol was a published protocol designed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult ALL. In this retrospective study, we analyzed 70 Chinese patients with adult ALL to compare the efficacy, safety and costs of HyperCVAD regimen in comparison to CALLG2008. METHODS: Pts ≥ 15 years old with previously untreated newly-diagnosed ALL were eligible. All pts provided IRB-approved informed consent before chemotherapy. HyperCVAD and CALLG2008 were given as initially described. Imatinib (400 mg daily) was administered concurrently in patients with Ph-positive ALL. Prophylactic antibiotics, antifungals, and antiviral agents were provided according to the institutional guidelines. Red blood cells and platelet transfusions were given for hemoglobin Primary endpoint of the study was CR rate after the first course of induction therapy. Complete remission (CR) was defined as having RESULTS: Thirty patients were treated with HyperCVAD, and 40 with CALLG2008. Pre-treatment characteristics are shown in the Table 1. After the first course of induction chemotherapy, complete remission was obtained in 83% and 78% of patients, respectively. The CR rate did not vary significantly by different regimens, gender, age, immunophenotype. However, 96% of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 76% of those without such evidence achieved a CR (P=0.045). In Ph-negative group, MRD-negative rates were found to be significantly higher with HyperCVAD (58% vs 27%, P=0.036). The median durations of neutrophil recovery of CALLG2008 group was 4 days longer than HyperCVAD group (P=0.038). Moreover, grade 3-4 thrombocytopenic ( CONCLUSION: Although HyperCVAD and CALLG2008 regimens showed relatively similar early CR rate, the former yields deep remissions more powerfully in Ph-negative ALL. Additionally, HyperCVAD was more favorable in hematopoietic recovery than CALLG2008. Differences were also observed in terms of less complications, shorter hospitalization and lower drug-related expenditure in favor of HyperCVAD group. Disclosures No relevant conflicts of interest to declare.

Low birthweight (LBW) is closely associated with fetal and perinatal mortality and morbidity. We identified the risk factors of LBW and geographical differences in LBW incidence in 30 Chinese provinces in the present study. This study was a population-based, retrospective cohort study performed in 30 Chinese provinces. We used data from the free National Pre-pregnancy Checkups Project, which is a countrywide population-based retrospective cohort study. To identify regional differences in LBW incidence, we used the Qinling-Huaihe climate line to divide China into northern and southern sections and the Heihe-Tengchong economic line to divide it into eastern and western sections. Multivariate unconditional logistic regression analysis with SAS 9.4 was used for data analysis. P

Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs) are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

Porous electrospun nanofibers, as new materials for solid-phase extraction, were synthesized by electrospinning and coupled with ultra high performance liquid chromatography and mass spectrometry to determine sulfonamide residues in environmental water. Aligned porous polystyrene electrospun nanofibers were fabricated under the mechanism of phase separation. The high-specific surface of these nanofibers (70 m(2)/g) could improve recoveries of the target sulfonamides 4-10 times compared with that of polystyrene nonporous material (3.8 m(2)/g). Under the optimized conditions, 13 sulfonamide residues showed an excellent linear relationship in the range of 0.125-12.5 ng/mL with a linear correlation coefficient (r(2)) greater than 0.99, and the detection limits of sulfonamides were as low as 0.80-5.0 ng/L. Compared to the commercial C18 and HLB columns, the homemade porous nanofibers columns had some merits including simple fabrication and extraction process, short process time and environmental friendliness. The optimized method was applied to eight water samples collected from different livestock farms (Xuzhou, China). The results showed that polystyrene porous nanofibers were promising to preconcentrate sulfonamides of different polarities in the waste water.

International audience

International audience; The building envelope plays a critical role in determining levels of comfort and building efficiency. Its real thermal properties characterization is of major interest to be able to diagnose energy efficiency performance of buildings (new construction and retrofitted existing old building). Research and development on a possible methodology for energy diagnostic of the building envelop is a hot topic and necessary trend. Many kinds of sensors and instruments are used for the studies. The application of infrared (IR) thermography in non-destructive evaluation has been widely employed for qualitative evaluations for building diagnostics; meanwhile, the IR thermography technology also has a large potentiality for the evaluation of the thermal characteristics of the building envelope. Some promising recent research studies have been carried out with such contactless measurement technique. Nevertheless, research efforts are still required for in situ measurements under natural environmental conditions. In order to develop new solutions for non-intrusive evaluation of local thermal performance, enabling quantitative assessment of thermal properties of buildings and materials, experiments were carried out on a multi-layer pratical scale wall fixed on a caisson placed in a climatic chamber. Six halogen lamps (1.5 kW for each lamp) placed in front of objective wall were used to emulate sunny conditions. The radiative heat flux emitted was monitored and modulated with time according to typical weather data set encountered in France. Both steady state and transient regime heat transfer were studied during these experiments. Contact sensors (thermocouples, heat flux meters, Peltier sensors) and non-contact sensors (thermal IR camera, pyranometer) were used to measure the temperatures and heat flux density evolution. It has to be noticed that the Peltier sensors have been tuned and used with a specific processing to set them compliant for heat flux density measurements. The measured data from different sensors were analysed and compared. The emissivity of wall surface and treated sensor surfaces were evaluated by using an IR camera with an adapted post-processing. Then, convective and radiative heat fluxes, at wall level, were estimated. Finally, the wall thermal properties can be calculated by using the measured temperatures and estimated heat fluxes using a dedicated thermal quadrupoles heat transfer model and an inverse method. This study aims at providing some guidelines for the choice of sensors, measurements protocol and adapted inverse model to be tested in real conditions on pilot situ scale. Aknowledgments : The Authors are very grateful to H2020 Built2Spec project for supporting this work.

The “hygiene hypothesis” is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found that S. japonicum infection downregulated airway hyperresponsiveness. The infiltrating cells, Th17 and Th2 effector cytokines in the bronchoalveolar lavage (BAL) fluids and lungs were significantly reduced in the infected mice. Our findings indicated that S. japonicum infection was able to effectively inhibit host’s allergic airway inflammation, which may be related to the upregulated Treg cells upon infection. To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms.

A series of indolin-2-one analogues were designed and synthesized, and all of them exhibited excellent in vitro potency. The structure and in vivo activity or toxicity relationship (in-vivo SAR) investigation of indolin-2-one structural analogues was carried out. In vivo efficacy studies indicated that 3b significantly suppressed tumor growth in HT-29 and NCI-H460 xenografts without causing significant loss of body weight. Kinase assay showed that compound 3b effectively inhibited the VEGFR-2, VEGFR-3, FLT3, Ret and PDGFR-β kinases, but had little effect on the VEGFR-1 kinase. Besides, 3b showed higher selectivity for VEGFR-2 compared with PDGFR-β. On the basis of its selectivity and safety properties, 3b was identified as a drug candidate for the treatment of cancer.

Heterologous expression is an efficient alternative to conventional extraction to produce a specific Buthus martensii Karsch (BmK) peptide. In this work, BmK1 was successfully expressed in Escherichia coli after genetic codon optimization, but BmK1 content was 13.9% of total protein) was obtained using a stronger promoter, PpJF325. Furthermore, a maximum BmK1 content (>21.7% of total protein) was obtained by combining promoter PpJF325 and three copies of the BmK1 gene. The yield of the purified BmK1 achieved 196.74 mg L−1 in E. coli BL21(DE3) pJF431, which was improved 2.09-fold compared with the control. This was the highest reported production of scorpion peptides in E. coli.

The total reflection of the wave will occur twice and the lightning over-voltage will be increased by 2 times when the lightning wave along the line reached in the disconnect switch are derived through the analysis of the accident 66kV transformer insulation breakdown. This will lead to the switch breakdown and discharge to be grounded. In this case the breaker is between the arrester and the transformer and the transformer will withstand 2 times arrester residual voltage result in the transformer breakdown. Finally, effective preventive measures combined with the practical experience are proposed.

Adduction of a nitric oxide moiety (NO•) to cysteine(s), termed S-nitrosylation (SNO), is a novel mechanism for NO to regulate protein function directly. However, the endothelial SNO-protein network that is affected by endogenous and exogenous NO is obscure. This study was designed to develop a quantitative proteomics approach using stable isotope labeling by amino acids in cell culture for comparing vascular endothelial growth factor (VEGFA)- and NO donor-responsive endothelial nitroso-proteomes. Primary placental endothelial cells were labeled with "light" (L-(12)C6 (14)N4-Arg and L-(12)C6 (14)N2-Lys) or "heavy" (L-(13)C6 (15)N4-Arg and L-(13)C6 (15)N2-Lys) amino acids. The light cells were treated with an NO donor nitrosoglutathione (GSNO, 1 mM) or VEGFA (10 ng/ml) for 30 min, while the heavy cells received vehicle as control. Equal amounts of cellular proteins from the light (GSNO or VEGFA treated) and heavy cells were mixed for labeling SNO-proteins by the biotin switch technique and then trypsin digested. Biotinylated SNO-peptides were purified for identifying SNO-proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Ratios of light to heavy SNO-peptides were calculated for determining the changes of the VEGFA- and GSNO-responsive endothelial nitroso-proteomes. A total of 387 light/heavy pairs of SNO-peptides were identified, corresponding to 213 SNO-proteins that include 125 common and 27 VEGFA- and 61 GSNO-responsive SNO-proteins. The specific SNO-cysteine(s) in each SNO-protein were simultaneously identified. Pathway analysis revealed that SNO-proteins are involved in various endothelial functions, including proliferation, motility, metabolism, and protein synthesis. We collectively conclude that endogenous NO on VEGFA stimulation and exogenous NO from GSNO affect common and different SNO-protein networks, implicating SNO as a critical mechanism for VEGFA stimulation of angiogenesis.

This study aimed to rapidly determine 13 representative sulfonamide (SA) residues in pork by using a surface-modified hydrophilic polystyrene sulfonic acid (PSSA) electrospun nanofibrous membrane as the solid-phase extraction (SPE) pretreatment sorbent, followed by ultra-performance liquid chromatography (UPLC) analysis. The highly hydrophilic nature of PSSA nanofibrous membrane created by vacuum plasma treatment was characterized using Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), water contact angle, and X-ray photoelectron spectroscopy (XPS) measurements. In the pretreatment procedures, 13 SA standards, which were spiked in the fatty pork samples, were extracted, enriched, and purified by the SPE procedure based on the principle of ion exchange with the sulfonic groups on the PSSA chains. Under the optimized conditions, the calibration curves of 13 SA compounds showed good linearities with correlation coefficients (r) of more than 0.99 in the range of 50.0-200 μg kg(-1). The mean recoveries of 13 SAs at the spiked concentrations of 50, 100, and 200 μg kg(-1) were in the range of 70.3-92.5 % with average RSDs (n = 6) of less than 15 % (except for sulfacetamide, 56.9-61.6 %). Compared with other pretreatment methods reported previously, less organic solvent (especially without degreasing the extract with n-hexane) was used in this time-saving SPE procedure, which avoids the possibility of emulsification and therefore enhances the recoveries. The developed and validated analysis method was sensitive, accurate, rapid, convenient, environmentally friendly, and was successfully applied for the detection of 13 SA residues in commercially available pork samples.

The purposes of measuring the transformer load losses and short-circuit impedance are checking whether they can meet the standard requirements. The traditional transformer short circuit test method were analyzed in theory and combined with engineering practice, how to improve test methods have been researched and explored is this paper. The proposed method can provide a good theoretical basis and experimental evidence for the transformer short circuit test. Introduction In power system, whether transformers are in reliable operation will cause a critical impact on the stability of power system. Short circuit test as the transformer factory, transfer, overhaul and the pilot project after the failure can ensure that the transformer can meet the electricity transmission quality and reliability requirements[1]. In practical engineering, however, due to the large capacity of the test transformer, if in accordance with the test transformer rated current for test, the desired test power capacity, and ancillary test equipment is difficult to meet the requirements, such as the test power supply capacity is not enough. The capacity and size of the regulator, the intermediate transformer and the capacitor are insufficient. Address these issues, this paper studies and discussions on how to improve the traditional transformer short circuit test methods can reduce the capacity of the existing pilot power, and reduce the size and weight of the test equipment [2]. Transformer short circuit test The main contents of the tests of the short circuit test is to test the transformer short-circuit impedance and load loss, which have very close relationship with transformer efficiency, parallel operation, and the system stability. When test equipment capacity is limited, usually field trials can test single-phase power source can have been used in three-phase transformer short circuit test on site. The test steps are as follows: first make the low voltage side leads short-circuit connection, then under rated frequency (50Hz), apply voltage to high side leads (AB, BC, CA) and measure the currents. Short-circuit test parameters have been measured three times when the applied voltage winding current reaches the rated current, and calculate the three-phase short-circuit K P and short-circuit impedance voltage K U . 2 K CA BC AB P P P P + + = (1) % 100 6 ) ( 3 % K × + + = N KCA KBC KAB U U U U U (2) Where, AB P 、 BC P 、 CA P are the two-phase load loss measured each time; N U is single-phase winding rated voltage, KAB U 、 KBC U 、 KCA U are the two-phase winding impedance voltage measured [3]. 4th International Conference on Machinery, Materials and Computing Technology (ICMMCT 2016) © 2016. The authors Published by Atlantis Press 1416 The improved method of transformer short circuit test When tested in accordance with the rated current of the test transformer, the capacity of the pilot power can be calculated as follows: N K K S S × = 100 % U (3) Where, K S is the desired short-circuit test power capacity (kVA); % k U is the percentage of transformer impedance voltage; N S is the test transformer rated capacity (kVA). Test power capacity is very large, so the requirements of large power capacity are unable to be met on site, and the regulator, the middle of the transformer should not meet the requirements either. In order to reduce the required test capacity, the method of parallel compensation capacitor is to be taken. Under the conditions of power frequency, the test transformer is inductive, so the test power is mainly used to provide the inductor current. The inductive current can be compensated by capacitive current. In accordance with the method described above to a large extent reduce the power capacity of the trial, but most likely for each test are more than ten pounds of weight over capacitor not only increased the floor space, transportation, handling, but also the wiring is difficult. Taking into account the relationship between the power frequency and capacity of the capacitor, the frequency of the pilot power can be increased on the basis of the installation of compensation capacitor and the power capacity and the compensation capacitor capacity can be reduced, and the capacitor size and weight can greatly be reduced. If the test transformer has been approximated by a series connection of inductance and resistance, the compensation capacitor and the test transformer form a parallel circuit[4]. 2 2 [ (2 ) ] L C R fL π = + (4) Resistance is very small, the compensation capacitor can be approximated inversely proportional with the power frequency square. When the power frequency is 3 times of the power frequency, the capacitor capacity approximately can be reduced to 1/9, the size and weight of the capacitor decreases [5]. Simulation The Triple-frequency Power test method can be simulated under the PSCAD environment. Figure 1 shows the simulation circuit, where T1 is the test transformer; the rated voltage is 66/11kV, the rated current 0.477/2.86kA; the rated capacity of the transformer is 31.5 MVA, the impedance voltage % K U = 10%, the secondary side of the T1 is shorted. Figure 1 The short circuit test simulation circuit Let the short circuit test be taken under the 50% rated capacitive current, the primary side test current N I1 5 . 0 = 0.2385kA; and at this time the measured primary voltage 1 U is 3.298kV. If all of the current is regarded as inductive, then the compensation capacitive current should also be 0.2385kA, the corresponding capacitor capacity is calculated as follows

Objective: ALK is a tyrosine kinase belonging to the insulin receptor super-family. The constitutively active ALK fusions are oncogenic and linked with multiple types of human cancer. The EML4-ALK fusion has been proven to be the driver of approximately 5% of NSCLC patients. We disclose here for the first time a novel ALK inhibitor WX-0593 and its preclinical evaluation data in preclinical models of ALK driven NSCLC. Method: The enzyme activities of WX-0593 for ALKWT, ALKL1196M, ALKC1156Y and EGFRL858R/T790M were measured with corresponding kinase assays. The anti-proliferative activity was evaluated in Karpas-299, Ba/F3, Ba/F3 (EML4-ALK-WT), Ba/F3 (EML4-ALK-L1196M), Ba/F3 (EML4-ALK-C1156Y), and NCI-H1975 cell lines. The specific effect (PD) of WX-0593 on ALK signaling was analyzed in NCI-H3122 cells. Antitumor activity of WX-0593 was evaluated in three patient-derived xenograft (PDX) models of NSCLC (LU-01-0015, LU-01-0319, and crizotinib resistant LU-01-0319R) and one cell-derived xenograft (CDX) model of NSCLC (NCI-H3122). PKPD was assessed by western blot analysis of the treated tumor tissues for p-ALK (Tyr1604), p-STAT3 (Tyr705), p-STAT5 (Tyr694), p-AKT, and p-ERK. Result: WX-0593 displayed potent enzymatic activities for ALKWT, ALKL1196M, ALKC1156Y and EGFRL858R/T790M with IC50 of 5.38, 9.26, 9.28, and 16.74 nM respectively. It also showed expected anti-proliferative activity in six cell lines, Karpas-299, Ba/F3, Ba/F3 (EML4-ALK-WT), Ba/F3 (EML4- ALK-L1196M), Ba/F3 (EML4-ALK-C1156Y), and NCI-H1975, with IC50 of 4.5, 2208, 4, 9.5, 9, and 508 nM, respectively. Western blot study in NCI-H3122 cells showed that WX-0593 could fully inhibit p-ALK, p-ERK,p-STAT5 at 11.1 nM and p-AKT at 100 nM. WX-0593 significantly inhibited tumor growth at all doses tested (P Conclusion: We have identified a potent orally active second generation ALK inhibitor, WX-0593. It can inhibit the activity of both wide type and crizotinib resistant ALK and showed strong antitumor activity in in vitro and in vivo preclinical models. These results are considered highly promising and warrant moving the compound forward to clinical investigation. Citation Format: Liu Xile, Charles Z Ding, Weifeng Mao, Yuxin Qin, Shansong Zheng, Yingying Yang, Qingmei Zheng, Long Zhang, Shuyong Zhao. Preclinical evaluation of WX-0593, a potent orally active ALK inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4794.

Sugarcane borer is the most common and harmful pest in Chinese sugarcane fields, and can cause damage to the whole plant during the entire growing season. To improve borer resistance in sugarcane, we constructed a plant expression vector pGcry2A0229 with the bar gene as the marker and the cry2A gene as the target, and introduced it into embryogenic calli of most widely cultivated sugarcane cultivar ROC22 by particle bombardment. After screening with phosphinothricin in vitro and Basta spray, 21 resistance-regenerated plants were obtained, and 10 positive transgenic lines harboring the cry2A gene were further confirmed by conventional PCR detection. Reverse transcription quantitative PCR (RT-qPCR) analysis showed that the copy number of the cry2A gene varied among different transgenic lines but did not exceed four copies. Quantitative ELISA analysis showed that there was no linear relationship with copy number but negatively correlated with the percentage of borer-infested plants. The analysis of industrial and agronomic traits showed that the theoretical sugar yields of transgenic lines TR-4 and TR-10 were slightly lower than that of the control in both plant cane and ratoon cane, nevertheless, TR-4 and TR-10 lines exhibited markedly lower in frequency of borer-infested plants in plant cane and in the ratoon cane compared to the control. Our results indicate that the introduction of the cry2A gene via bombardment produces transgenic lines with obviously increased stem borer resistance and comparable sugar yield, providing a practical value in direct commercial cultivation and crossbreeding for ROC22 has been used as the most popular elite genitor in various breeding programs in China.

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) mediates vascular endothelial growth factor (VEGF)-stimulated endothelial cytoskeleton remodeling and migration; however, the underlying mechanisms are elusive. Covalent adduction of a NO moiety (NO(•)) to cysteines called S-nitrosylation (SNO) is a key NO signaling pathway. The small actin-binding protein cofilin-1 (CFL1) is essential for actin cytoskeleton remodeling. We investigated whether S-nitrosylation regulates CFL1 function and endothelial cytoskeleton remodeling and migration upon VEGF stimulation. VEGF rapidly stimulated S-nitrosylation of CFL1, which was blocked by NO Synthase inhibition and eNOS knockdown by specific eNOS-siRNA. Cys80 and Cys139 were identified as the major SNO-sites in CFL1 by LC-MS/MS. The actin severing activity of recombinant SNO-mimetic CFL1 (C80/139A DMA-CFL1), but not SNO-deficient CFL1 (C80/139S DMS-CFL1), was significantly greater than that of wild-type CFL1 (wt-CFL1). When wt-CFL1 and its mutants were overexpressed in endothelial cells, basal actin bound wt-CFL1 was undetectable but significantly increased by VEGF; basal actin bound DMA-CFL1 was readily high and basal actin bound DMS-CFL1 was detectable but low, and both were unresponsive to VEGF. Treatment with VEGF significantly increased filamentous (F-) actin and filopodium formation and cell migration in endothelial cells. Overexpression of wt-CFL1 inhibited VEGF-induced F-actin formation. Overexpression of DMA but not DMS CFL1 decreased basal but not VEGF-stimulated F-actin formation. Overexpression of DMA but not DMS CFL1 suppressed VEGF-stimulated filopodium formation and migration in endothelial cells. Thus, S-nitrosylation of CFL1 provides a novel signaling pathway post-NO biosynthesis via eNOS-derived NO for endothelial cytoskeleton remodeling and migration upon VEGF stimulation.

Through several examples, describes the harmonic distribution network and its equipment hazards. Harmonics can cause distribution transformers demonstration power loss and additional loss increases, resulting in reduced aging transformer oil and insulation properties, triggering a distribution transformer discharge breakdown or burn accidents; harmonics is amplified in a capacitor bank, and cause the capacitor bank fuse group burst, tripping and other accidents; harmonics cause the motor to reverse, vibration, noise and temperature; harmonic electromagnetic voltage transformer prone to occur ferromagnetic resonance over-voltage; harmonics resulting in increased distribution network line losses. Awareness and understanding harmonics, harmonic provide for effective governance scientific theory. Introduction Nonlinear load and impact load when produce can produce harmonics, and the distribution of injection, if is the injection of harmonic frequency (50 Hz) 2, 3, 5, 7 times the size of an integer, is the high frequency[1-3]. If the injection of harmonic frequency (50 Hz) 1/2, 1/3, several times, 2/3, 2/5, 1/5 is the frequency division; Harmonic pollution to the power system is not allow to ignore, because electric furnace, electric arc furnace, electrolytic furnace, intermediate frequency furnace and other commonly used straight in 10 kV power distribution net, so the nonlinear load and as the direct input to the distribution of harmonic sources, will cause the current, voltage waveform distortion, distribution network harmonic generation. Harmonic produces serious pollution to power network, and even equipment in distribution network transformer, capacitor Banks, motor, voltage transformer, such as destructive, and lead to distribution network line loss increase[4, 5]. Figure 1 The 10kV substation system wiring diagram Harmonic harm to distribution transformer (1)Accident cases Figure 1 is for a 10 kV substation system wiring diagram, Oriental carbon factory main production machinery: crusher, milling machine, calcinations furnace, vibrating screen, press

We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies.

Loxoprofen (LOXO) is a non-steroidal anti-inflammatory drug. Repeated oral administrations induce gastrointestinal side effects. Patches are a promising alternative.The aim of this study was to investigate the effects of organic amines on the skin permeation of LOXO and finally design a patch with a comparable permeation profile and pharmacodynamic effects to the commercial LOXONA® plaster.The effects of organic amines were assessed by flux values of LOXO from isopropyl myristate (IPM), using horizontal diffusion cell and rabbit skin. FTIR spectroscopy was used to confirm ion-pair formation. Anti-inflammatory and analgesic activity assessments were performed in the adjuvant arthritis rat model and acetic acid-induced writhing syndrome in mouse, separately.Results showed that triethylamine (TEA) was the most potential candidate in IPM, with the highest flux of 499.75 ± 32.40 µg/cm(2)/h. In patch, the highest flux of 369.37 ± 34.32 µg/cm(2)/h was still obtained by LOXO-TEA. Combined with penetration enhancers, the cumulative amounts were further increased in presence of 5% IPM, which exhibited a flux of 840.04 ± 66.38 µg/cm(2)/h as two times of the commercial one. Ultimately, anti-inflammatory and analgesic activity assessment presented that a comparable pharmacodynamic activity with the commercial one could be obtained by the patch we designed. Additionally, we also found that LOXO patch applied topically exerted a systemic effect, and the effect was dose-dependent.It was feasible for LOXO patch design by combination of ion-pair technology and chemical enhancers.

During the process of laser propagation in free space, energy attenuation is brought by atmospheric medium. One of the major problems about laser propagation is that atmospheric component does not remain constant within the whole altitude band. So working out the relatively accurate attenuation coefficient is a research interest of many researches for several years. On this basis of analysis of the atmospheric component distributing characteristic, simple and practical simulate approach was given to meet the needs of laser rangefinder. The main work is the research on 1.06μm YAG laser transmission characteristics in the atmosphere, and the atmosphere loss of the mathematical model is investigated. The paper discussed the influence of atmospheric attenuation on ranging ability of laser rangefinder and analyzed the atmospheric attenuation theoretical. It showed that when the attenuation coefficient γ increases the detectable distance decreases rapidly. In the condition of three transmission modes, which are ground-to-ground mode, ground-to-air mode and air-to-air mode, the relationships between atmospheric transmittance and different visibility, different zenith angle were analyzed. Minimal detectable power of laser rangefinder represents ranging ability in above-mentioned three different modes was formulated with atmospheric transmittance. Based on the results, we can adjust the experimental parameters and achieve more desirable results. It has positive influence for the design of laser rangefinder.

In this paper, we investigated the characteristic of radar target, the spherical and the pyramidal missile warheads, and compared the RCS and performance of the targets with and without the cover of the plasma metamaterials. Numerical simulation is obtained by the numerical calculation Finite-difference time-domain method (FDTD). The parameters of plasmonic structures as a metamaterial cloak was designed and optimized. The relationship between the parameters of the cloak and the corresponding electromagnetic characteristic of the target are analyzed by the simulation and discussion in broadband radar signals. After optimization, the plasma cover could attenuate 40 dBsm of the radar cross section (RCS) of the targets maximally. The result shows that the anomalous phenomenon of cloaking and stealth effects induced by plasma materials for the radar target, which might have potential application of military affairs.

To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs.

Elimination of aberrantly folded polypeptides from the endoplasmic reticulum (ER) by the ER-associated degradation (ERAD) system promotes cell survival under stress conditions. This quality control mechanism requires movement of misfolded proteins across the ER membrane for targeting to the cytosolic proteasome, a process facilitated by a "holdase" complex, consisting of Bag6 and the cofactors Ubl4A and Trc35. This multiprotein complex also participates in several other protein quality control processes. Here, we report SGTA as a component of the Bag6 system, which cooperates with Bag6 to channel dislocated ERAD substrates that are prone to aggregation. Using nuclear magnetic resonance spectroscopy and biochemical assays, we demonstrate that SGTA contains a noncanonical ubiquitin-like-binding domain that interacts specifically with an unconventional ubiquitin-like protein/domain in Ubl4A at least in part via electrostatics. This interaction helps recruit SGTA to Bag6, enhances substrate loading to Bag6, and thus prevents the formation of nondegradable protein aggregates in ERAD.