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Background: Subcutaneous immunotherapy (SCIT) is now the only treatment that can modify the natural course of allergic rhinitis (AR). However, not all children with AR benefit from SCIT. Objective: To evaluate the efficacy of SCIT in dust-mites-induced AR children and explore correlative factors predicting treatment response to SCIT. Methods: 225 children aged 4–17 years old with AR were recruited from January 2016 to September 2019, and monitored at baseline, 4, 12, and 24 months after the start of SCIT treatment. The visual-analogue-score (VAS) was used to assess the clinical symptoms. Multivariate binary logistic regression analyses and receiver operating characteristic curves were used to explore correlative factors in predicting the efficacy of SCIT. Results: The significant declines in VAS started after 4 months of SCIT and continued to improve throughout the study compared with baseline. An increase in children’s age (OR=0.688, 95%CI: 0.479–0.988) and those with allergic history (OR=0.097, 95%CI: 0.009–1.095) were negatively associated with the risk of poor efficacy. Polysensitized children were more likely to suffer poor efficacy (OR=15.511 95%CI: 1.319–182.355). The clinical response at month 4 (r=0.707) and month 12 (r=0.925) was related to that at month 24. The area under the curve (AUC) for improvement at month 4 and month 12 was 0.746 and 0.860, respectively. Conclusion: Our study confirmed the clinical efficacy of SCIT in AR children. Children with younger age, negative allergic history, and multiple allergens may predict a worse efficacy. The onset of action and the clinical response to SCIT in the second year can be predicted as early as by month 4.

Xanthomonas oryzae pv. oryzae (Xoo) is a notorious plant pathogen that causes leaf blight of rice cultivars. The pathogenic bacteria possess numerous transcriptional regulators to regulate various biological processes, such as pathogenicity in the host plant. Our previous study identified a new master regulator PXO_RS20790 that is involved in pathogenicity for Xoo against the host rice. However, the molecular functions of PXO_RS20790 are still unclear. Here, we demonstrate that transcriptional regulator Sar (PXO_RS20790) regulates multiple secretion systems. The RNA-sequencing analysis, bacterial one-hybrid assay, and electrophoretic mobility shift assay revealed that Sar enables binding of the promoters of the T1SS-related genes, the avirulence gene, raxX, and positively regulates these genes' expression. Meanwhile, we found that Sar positively regulated the T6SS-1 clusters but did not regulate the T6SS-2 clusters. Furthermore, we revealed that only T6SS-2 is involved in interbacterial competition. We also indicated that Sar could bind the promoters of the T3SS regulators, hrpG and hrpX, to activate these two genes' transcription. Our findings revealed that Sar is a crucial regulator of multiple secretion systems and virulence.

Sulfate radical (•SO4−)-based advanced oxidation processes are widely used for wastewater treatment. This study explored the potential use of UV/persulfate (UV/PS) system for the degradation of 17β-estradiol (E2). The pH of the reaction system can affect the degradation rate of E2 by UV/PS and the optimum pH was 7.0; Br− and Cl− in water can promote the degradation rate, HCO3− has an inhibitory effect on the reaction, SO42− and cations (Na+, Mg2+, K+) have no effect on the degradation rate. The degradation of E2 by UV/PS was a mineralization process, with the mineralization rate reaching 90.97% at 8 h. E2 in the UV/PS system was mainly degraded by hydroxylation, deoxygenation, and hydrogenation. E2 reaction sites were mainly located on benzene rings, mainly carbonylation on quinary rings, and bond breakage between C10 and C5 resulted in the removal of benzene rings and carboxyl at C2 and C3 sites. In the presence of halogen ions, halogenated disinfection by-products were not formed in the degradation process of E2 by UV/PS. E2 in the UV/PS system could inhibit the formation of bromate. The results of this study suggest that UV/PS is a safe and reliable method to degrade E2. HIGHLIGHTS The reaction kinetics, mechanisms and degradation pathways of the UV/PS process in degrading E2 in marine aquaculture water were elucidated.; The fates of E2 in marine aquaculture water were analyzed in the presence of potential interfering factors such as anions (Br−, Cl−, HCO3−, SO42−), cation (Na+, Mg2+, K+) and pH value.; The inorganic disinfection by-products namely bromate of E2 treated by UV/PS was also explored.

Background: Immune checkpoint inhibitors (ICIs) have transformed the prognosis of patients with advanced lung squamous cell carcinoma (SCC). As the use of checkpoint inhibitors increases in a variety of malignancies, immune-related adverse effects will become more common.Case report: Here, we present a case of a 64-year-old man with advanced stage lung SCC who developed hyponatremia and hypophysitis after treatment with ipilimumab and nivolumab. The patient underwent effective treatment with steroids, hyperosmolar therapy, and fluid restriction.Conclusion: This case highlights the potentially life-threatening complications of ICIs, and it shows that early recognition and complete evaluation are critical in clinical practice.

PCa is a disease with a wide range of tissue patterns and this adds to its classification difficulty. Moreover, the data source heterogeneity, i.e. inconsistent data collected using different machines, under different conditions, by different operators, from patients of different ethnic groups, etc., further hinders the effectiveness of training a generalized PCa classifier. In this paper, for the first time, a Generative Adversarial Network (GAN)-based three-player minimax game framework is used to tackle data source heterogeneity and to improve PCa classification performance, where a proposed modified U-Net is used as the encoder. Our dataset consists of novel high-frequency ExactVu ultrasound (US) data collected from 693 patients at five data centers. Gleason Scores (GSs) are assigned to the 12 prostatic regions of each patient. Two classification tasks: benign vs. malignant and low- vs. high-grade, are conducted and the classification results of different prostatic regions are compared. For benign vs. malignant classification, the three-player minimax game framework achieves an Area Under the Receiver Operating Characteristic (AUC) of 93.4%, a sensitivity of 95.1% and a specificity of 87.7%, respectively, representing significant improvements of 5.0%, 3.9%, and 6.0% compared to those of using heterogeneous data, which confirms its effectiveness in terms of PCa classification.

The prevalence of malnutrition is high among oncology patients in Northern China. Malnutrition is related to the longer hospital stay, and it can be used to predict the prognostic outcome of patients. This work focused on investigating the relationship of nutritional condition with the length of hospital stay (LOS) in Northern Chinese patients with lung adenocarcinoma (LUAD). The Patient-Generated Subjective Global Assessment (PG-SGA), Nutritional Risk Screening 2002 (NRS 2002) score, recent weight loss and BMI were assessed in a probabilistic sample of 389 LUAD patients without epidermal growth factor receptor (EGFR) mutations. This study collected the demographic and clinical features of patients in a prospective manner. Then, we examined the association of nutritional status with LOS among the population developing LUAD. According to the PG-SGA, 63 (16·3 %), 174 (44·7 %) and 78 (20·1 %) patients were at risk for undernutrition, moderate undernutrition and severe undernutrition, respectively. Nutritional risk was found in 141 (36·2 %) patients based on the NRS 2002. The average LOS for tumour patients in Northern China was 12·5 d. At admission, a risk of undernutrition or undernutrition according to the PG-SGA (P < 0·001), NRS 2002 (P < 0·001) and latest weight loss (P < 0·001) predicted the longer LOS. LOS was related to nutritional status and hospitalisation expenses (P < 0·001). LUAD patients who stayed in the ICU had a poorer nutritional status and a longer LOS (P < 0·001). In Northern Chinese patients with LUAD, a risk for undernutrition evaluated by the PG-SGA, the NRS 2002 and recent weight loss, but not BMI, could predict a longer LOS.

The effects of water matrices on the reaction kinetics and transformation products of roxithromycin (ROX) with sodium hypochlorite (NaClO) were investigated. It was found that the removal efficiency of ROX was dependent on the type of disinfected water. For simulated fresh water, marine culture water and seawater, the reaction rate constant was 0.0521 min−1, 0.0757 min−1 and 0.106 min−1, respectively. The bromide ions in seawater and marine culture water not only promoted the reaction of ROX with NaClO but also caused the generation of brominated DBPs (Br-DBPs). Four DBPs including one chlorinated DBP (Cl-DBP) and three Br-DBPs were identified. The cladinose moiety and C14 atom were the main reaction centers which were easily attacked by disinfectant in fresh water. The desosamine moiety was also broken away from the parent compound ROX in the simulated marine culture water and seawater. Adsorbable organic halogen (AOX) analysis demonstrated that the Br-DBPs in water samples containing bromide ions were generally more carcinogenic than the Cl-DBPs formed in fresh water.

A novel amino-functionalized hydrothermal biochar modified with nitric acid and nicotinamide (NMSH) was prepared and applied to remove heavy metal in different systems. The study of batch adsorption found that NMSH had different adsorption behaviors for Cr(VI) and Sb(V), and different concentrations of heavy metal ions exhibited different coadsorption behaviors in mixed system. NMSH had great anti-interference ability to coexisting inorganic ion and humic substance. The maximum adsorption capacity of NMSH was 132.74 mg/g for Cr(VI), and 241.92 mg/g for Sb(V). Moreover, different interfering ions and matter had different effects on adsorption. The mechanism study found that the adsorption mechanism of NMSH involved multiple interactions, and the mechanisms were different. Some O-containing functional groups of NMSH could reduce Cr(VI) to Cr(III), but not Sb(V). NMSH had great removal efficiency and reusability performance, which suggested that NMSH had prospects for practical wastewater treatment.

Zr/CTAB/BAC was prepared by bamboo activated carbon (BAC) functionalised by zirconia chloride octahydrate (ZrOCl2·8H2O) and Cetyltrimethylammonium bromide (CTAB). The effects of temperature, time, Zr dosage and CTAB concentration on removing phosphate and nitrate (H2PO4− and NO3−) in wastewater were investigated. The structure of Zr/CTAB/BAC was characterized by SEM, BET, FTIR, XRD and TG, and the kinetics and thermodynamics of adsorption were discussed. The optimum preparation conditions were as follows: the modification temperature was 25 °C, the modification time was 4 h, the mass of the modifier Zr added was 0.40 g, and the concentration of the modifier CTAB was 0.6 mM. When the dosage of Zr/CTAB/BAC was in the range of 0.1 g–1.0 g, the removal efficiency of phosphate in simulated wastewater was between 59.32% and 99.42%, and the removal efficiency of nitrate was between 34.08% and 93.70%. Using NaOH as a regenerant, after four times adsorption and desorption experiments, the removal efficiency of phosphate and nitrate by Zr/CTAB/BAC can still reach more than 70%. The chemical adsorption was the primary cause of the adsorption, and the adsorption process was endothermic. Zr/CTAB/BAC had an obvious removal effect on phosphate and nitrate in water, which could be promoted to treat other anionic salts in sewage.

In this work, a novel sludge biochar/Zn–Al layered double hydroxide composite (SL) was synthesized in a facile co-precipitation method, and it was used to simultaneously remove benzotriazole (BTA) and lead ion (Pb(II)). Batch adsorption experiments demonstrated that composites with sludge content of 1.0 g (SL-1.0) had a great adsorption performance for BTA and Pb(II). The maximum adsorption capacities of SL-1.0 for BTA and Pb(II) were 239.6 and 226.1 mg g−1, respectively. There was preferential adsorption of BTA in BTA and Pb(II) binary system. The adsorption mechanism analysis indicated that the BTA and Pb(II) adsorption involved electrostatic attraction and chemical bonding with surface functional groups on SL-1.0. Specifically, hydrogen bonding and π-π interaction were mainly ascribed to BTA adsorption, while complexation with surface function groups dominated Pb(II) adsorption. With the advantages of facile synthesis and excellent adsorption capacity, SL-1.0 possesses great potential for simultaneously removing of BTA and Pb(II) from wastewaters.

During chlorine disinfection process, reactions between the disinfectant and 17β-estradiol (E2) lead to the formation of halogenated disinfection byproducts (DBPs) which can be a risk to both ecosystem and human health. The degradation and transformation products of E2 in sodium hypochlorite (NaClO) disinfection processes of different water samples were investigated. The reaction kinetics research showed that the degradation rates of E2 were considerably dependent on the initial pH value and the types of water samples. In fresh water, synthetic marine aquaculture water and seawater, the reaction rate constant was 0.133 min−1, 2.067 min−1 and 2.592 min−1, respectively. The reasons for the above phenomena may be due to the different concentrations of bromide ions (Br−) in these three water samples which could promote the reaction between NaClO and E2. Furthermore, Br− could also cause the formation of brominated DBPs (Br-DBPs). The main DBPs, reaction centers and conceivable reaction pathways were explored. Seven halogenated DBPs have been observed including three chlorinated DBPs (Cl-DBPs) and four Br-DBPs. The active sites of E2 were found to be the pentabasic cyclic ring and the ortho position of the phenol moiety as well as C9-C10 position. The identified Cl/Br-DBPs were also confirmed in actual marine aquaculture water from a shrimp pond. The comparison of bio-concentration factors (BCF) values based on calculation of EPI-suite showed that the toxicities of the Br-DBPs were stronger than that of their chloride analogues. The absorbable organic halogens (AOX) analysis also suggested that the DBPs produced in the marine aquaculture water were more toxic than that in the fresh water system.

The fates of the antibiotic sulfamethoxazole (SMX) in the chlorination of fresh water, simulated brackish marine culture water, and marine water were investigated. SMX was oxidized by sodium hypochlorite (NaClO) at different reaction rates in the different samples. The oxidation of SMX followed pseudo-first-order kinetics, and the rate constant was the largest in marine water (3.44 min−1), as Br− ions promote the oxidation reaction. Moreover, the kinds of disinfection byproducts (DBPs) were also affected by Br− ions. Br-DBPs were found in the simulated brackish marine culture water and marine water disinfection systems. The structures of the DBPs indicated that S-C cleavage, polymerization, S-N hydrolysis, chlorine/bromine substitution, and desulfonation reactions occurred on SMX during the disinfection process. EPI (Estimation Programs Interface) Suite™ and absorbable organic halogen (AOX) analysis were used to evaluate the toxicity of the DBPs. The results suggested that DBPs in the simulated brackish marine culture water and marine water systems were more toxic than those in the fresh water system.

Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs, however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly up-regulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease. Notably, intratracheal administration with SHH- neutralizing antibody or cyclopamine robustly attenuates goblet cell phenotypes in mouse models with allergic airway disease. Finally, we identify that Muc5AC gene encoding MUC5AC mucin serves as a direct target of GLI transcriptional factors in response to SHH, whereas the SAM pointed domain-containing ETS transcription factor and Forkhead box A2, critical transcriptional factors for goblet cell phenotypes, both function as the effectors of GLIs in response to SHH stimulation. Together, the up-regulation of SHH expression in allergic bronchial epithelia contributes to goblet cell metaplasia; thus, blockage of SHH signaling is a rational approach in a therapeutic intervention of epithelial remodeling in chronic airway diseases.

The two-component signal transduction system PhoBR regulates the adaptation to phosphate limitation and the virulence of many animal bacterial pathogens. However, PhoBR in phytopathogens has rarely been investigated. In this study, we found that PhoBR in Xanthomonas oryzae pv. oryzae (Xoo), the pathogen of rice bacterial leaf blight, also regulates the adaptation to phosphate starvation. Unexpectedly, rice leaves infected by the phoBR-deleted mutant and wild-type PXO99A showed similar lesions, indicating that PhoBR is unnecessary for the virulence of Xoo. phoBR was found to be silenced during host infection, whereas artificially constitutive PhoBR expression attenuated virulence on host rice and growth in phosphate-rich media. RNA-sequencing (RNA-seq) was then performed to investigate the global effect caused by constitutive PhoBR activation. RNA-seq and further experiments revealed that the PhoBR regulon in Xoo comprised a wide range of genes. Nutrient transport and metabolism readjustments that resulted from PhoBR regulon activation may be responsible for growth attenuation. Our findings suggest that growth reduction regulated by PhoBR is a fitness cost of adaptation to phosphate starvation. PhoBR in Xoo is activated under phosphate-limited conditions, which could exist in epiphytic and saprophytic surviving phases, and is strictly repressed within phosphate-rich host plants to minimize fitness costs.

We developed a novel approach to determine formamidopyrimidine DNA glycosylase (FPG) activity by taking advantage of target-induced self-primed rolling circle amplification (RCA) and magnetic nanoprobes. Herein, a unique nick (8-oxoguanine, 8-oxoG) was positioned in duplex DNA containing P-circle and P1, which together serve as a FPG substrate, RCA template, and RCA primer probe. The presence of FPG specifically binds 8-oxoG and cleaves the P-circle into two parts, producing 5'-phosphoryl termini. A phosphodiester bond between the 5'-phosphoryl and 3'-hydroxyl termini was formed with the addition of T4 DNA ligase, producing an unnicked circular strand. Using the unnicked strand as the RCA template, the P1 hybridized with the circle probe as a primer will trigger the RCA process. The RCA reaction produces amounts of long tandem-repeat DNA tiles with multiple recognizing regions for the FAM modified DNA probes (FP) and biotin-modified DNA probes (BP). With the streptavidin-biotin interaction, the BPs and FPs can be easily immobilized on the surface of streptavidin-modified magnetic microbeads (MBs). Due to the RCA enhanced and highly-concentrated fluorescence accumulation on the MBs, an ultralow detection limit of 1.033 U mL-1 for FPG was obtained. Combined with the high tolerance capability of human blood serum owing to magnetic isolation, the FPG assays in human blood serum were also obtained using fluorescence and confocal laser scanning microscopy. These results indicate that this robust self-primed RCA combined with magnetic nanoprobes is an excellent candidate for quantitatively monitoring the FPG activity responsible for DNA oxidative damage-related clinical diagnosis and therapy.

Histopathology of Hematoxylin and Eosin (H&E)-stained tissue obtained from biopsy is commonly used in prostate cancer (PCa) diagnosis. Automatic PCa classification of digitized H&E slides has been developed before, but no attempts have been made to classify PCa using additional tissue stains registered to H&E. In this paper, we demonstrate that using H&E, Ki67 and p63-stained (3-stain) tissue improves PCa classification relative to H&E alone. We also show that we can infer PCa-relevant Ki67 and p63 information from the H&E slides alone, and use it to achieve H&E-based PCa classification that is comparable to the 3-stain classification. Reported improvements apply to classifying benign vs. malignant tissue, and low grade (Gleason group 2) vs. high grade (Gleason groups 3,4,5) cancer. Specifically, we conducted four classification tasks using 333 tissue samples extracted from 231 radical prostatectomy patients: regression tree-based classification using either (i) 3-stain features, with a benign vs malignant area under the curve (AUC = 92.9%), or (ii) real H&E features and H&E features learned from Ki67 and p63 stains (AUC = 92.4%), as well as deep learning classification using either (iii) real 3-stain tissue patches (AUC = 94.3%) and (iv) real H&E patches and generated Ki67 and p63 patches (AUC = 93.0%) using a deep convolutional generative adversarial network. Classification performance was assessed with Monte Carlo cross validation and quantified in terms of the Area Under the Curve, Brier score, sensitivity, and specificity. Our results are interpretable and indicate that the standard H&E classification could be improved by mimicking other stain types.

A novel cost-effective hydrochar composite (MgSi-HC) prepared by a simple one-step process using waste sawdust, inexpensive silicate and magnesium salts as raw materials was used to remove Cu(II), Zn(II), and tetracycline (TC) from aqueous solution. The novel hydrochar material was characterized by SEM, TEM, XRD, BET specific surface area, ATR-FTIR spectra, and X-ray photoelectron spectroscopy. The values of surface area (107.7 m2/g) and pore volume (0.489 cc/g) of MgSi-HC indicated that it had a large specific surface area and well-developed pore structure. Adsorption isotherm showed that the maximum adsorption capacity of MgSi-HC for Cu(II), Zn(II), and TC was 214.7 mg/g, 227.3 mg/g, and 361.7 mg/g, respectively. In addition, the effects of heavy metals and tetracycline on each other in binary adsorption systems were different. Meanwhile, the study of mechanism indicated that various interactions might be involved in the adsorption process, and the adsorption mechanisms of heavy metal and TC were different. The potential of MgSi-HC for practical environmental remediation was evaluated, the result demonstrated that MgSi-HC still had high performance after 5 adsorption-desorption cycles, and it had stable adsorption ability in different water samples (150.2–156.2 mg/g for Cu, 159.6–167.4 mg/g for Zn, and 183.9–189.8 mg/g for TC), implying that the novel hydrochar could be a promising adsorbent for removal of heavy metal and antibiotics from real wastewater. This work provided a reference on the coadsorption of heavy metal and antibiotics, and indicated the potential application of MgSi-HC in complex pollutant adsorption.

Sulfate radical (SO4 −) based advanced oxidation processes are effective for the removal of antibiotics including sulfonamides from freshwater. However, few studies were focused on the degradation of sulfonamides in marine aquaculture water and seawater, as well as the impact of transformation products on seafood such as fishes. In this work, sulfamethoxazole (SMX) was treated with UV/persulfate (UV/PS) system in different water samples. Chloride ions (Cl−) had an inhibitory effect possibly due to the consumption and mutual quenching of reactive radicals. A slight promotion by bromide ions (Br−) was observed and should be related not only to the transformation of Br , but also to the properties of the SMX itself. Bicarbonate ions (HCO3–) significantly inhibited degradation as it is a scavenger of SO4 − and HO in UV/PS. Sulfate ions (SO42−) showed a negligible impact on SMX degradation. The active sites of SMX were calculated to be the N1 and C7 atoms of the isoxazole ring, as well as the C9, C13 and N3 atoms of the benzene ring. Seven organic transformation products were identified by LC-MS/MS. Bromate (BrO3−) and chloromethane as the potential human carcinogens were not detected from the reaction system of UV/PS with SMX in marine aquaculture water and seawater. Preliminary analysis of toxicity by the EPI Suite model, absorbable organic halogen (AOX) analysis and growth inhibition of Chlorella vulgaris proved that the UV/PS process could be used as a new disinfection method and it is relatively safer than traditional UV/NaClO disinfection.

We have integrated shear wave elasticity, Doppler flow imaging, and photoacoustic tomography into the SonixEm-brace automated breast ultrasound scanner (ABUS). This system can acquire a multimodal volumetric scan of the entire breast in under ten minutes. We present here a series of phantom studies demonstrating the capabilities of this combined system for the first time. We imaged a commercially available elastography training phantom, measuring the stiffness of the background material to be 17.5 ± 0.1 kPa and the stiffness of the inclusions to be 32.3 ± 0.3 kPa, as compared to the manufacturer's provided values of 20 ± 5 kPa and ~40 kPa, respectively. We imaged a knotted tube phantom, demonstrating the computation and scan conversion of volumetric Doppler flow data. Finally, we developed and imaged a multimodal phantom incorporating inclusions which are uniquely visible in either elasticity or photoacoustic imaging.

The antibacterial agent norfloxacin (NOR) and sodium hypochlorite (NaClO), which are both widely used in marine culture, react with each other to form the halogenated disinfection byproducts (X-DBPs). The effects of the water characteristics and iodide concentration on the reaction kinetics were investigated. The results showed that the reaction rate of NOR with NaClO increases from 0.0586 min−1 to 0.1075 min−1 when the iodide concentration was changed from 0 μg−1 to 50 μg−1. This demonstrated the enhancement of NOR oxidation in the presence of iodide ions. Four novel iodinated DBPs (I-DBPs) were identified in the marine culture water. Iodine substitutions occurred at the C3 and C8 positions of NOR. The formation mechanisms of X-DBPs in the marine culture water were proposed based on the intermediate and final products. NOR may undergo a ring-opening reaction, a de-carbonyl reaction and substitution to form intermediates and finally generate the X-DBPs. Furthermore, the predicted logKOW and logBCF values of the I-DBPs were higher than that of the Br-DBPs and Cl-DBPs. The AOX concentration in the synthetic water samples decreased in the following order: seawater (8.49 mg L−1) > marine culture water (4.05 mg L−1) > fresh water (1.89 mg L−1). The amount of AOX also increased with the increase in iodide concentration. These results indicated that the I-DBPs were more toxic than their brominated and chlorinated analogues.

Surface tension and specular neutron reflectivity measurements have been used, for the first time to systematically study both the interfacial structure and composition of monolayers of the soluble surfactant, sodium dodecyl sulfate containing a low-dose, poorly water soluble drug, testosterone enanthate. Modelling of the specular neutron reflectivity data suggests that the hydrophobic testosterone enanthate was adsorbed in the C12 hydrophobic tail region of the surfactant monolayer, regardless of the concentration of surfactant at the interface and whether or not additional drug was added to the interface. The location of the hydrophobic drug in the tail region of the surfactant monolayer is supported by the results of classical, large-scale molecular dynamics simulations. The thickness of the surfactant monolayer obtained, in the presence and absence of drug, using molecular dynamics simulations was in good agreement with the corresponding values obtained from the specular neutron reflectivity measurements. The stoichiometry of surfactant:drug at the air-water interface at sodium dodecyl sulfate concentrations above the critical micelle concentration was determined from specular neutron reflectivity measurements to be approximately 3 : 1, and remained constant after the spreading of further testosterone enanthate at the interface. Significantly, this stoichiometry was the same as that obtained in the micelles from bulk solubilisation studies. Important insights into the preferred location of drug in surfactant monolayers at the air-water interface as well as its effect on the structure of the monolayer have been obtained from our combined use of experimental and simulation techniques.

The two‐component signal transduction system PhoBR regulates the adaptation to phosphate limitation and the virulence of many animal bacterial pathogens. However, PhoBR in phytopathogens has rarely been investigated. In this study, we found that PhoBR in Xanthomonas oryzae pv. oryzae (Xoo), the pathogen of rice bacterial leaf blight, also regulates the adaptation to phosphate starvation. Unexpectedly, rice leaves infected by the phoBR‐deleted mutant and wild‐type PXO99(A) showed similar lesions, indicating that PhoBR is unnecessary for the virulence of Xoo. phoBR was found to be silenced during host infection, whereas artificially constitutive PhoBR expression attenuated virulence on host rice and growth in phosphate‐rich media. RNA‐sequencing (RNA‐seq) was then performed to investigate the global effect caused by constitutive PhoBR activation. RNA‐seq and further experiments revealed that the PhoBR regulon in Xoo comprised a wide range of genes. Nutrient transport and metabolism readjustments that resulted from PhoBR regulon activation may be responsible for growth attenuation. Our findings suggest that growth reduction regulated by PhoBR is a fitness cost of adaptation to phosphate starvation. PhoBR in Xoo is activated under phosphate‐limited conditions, which could exist in epiphytic and saprophytic surviving phases, and is strictly repressed within phosphate‐rich host plants to minimize fitness costs.

The quality of the project depends firstly on the design. Selected excellent design units can help the owner to realize the projects quality, cost and schedule target. The principles of the evaluation in design bidding were discussed in this paper. The design quality, design fees quotation, design teams service commitments, design teams ability, design institutions strength, and design institutions reputation were given as the six aspects of evaluation index system. last, the organization of evaluator was discusses.

A variety of vasoactive stimuli induce endothelial permeability through Rac1, a membrane of Rho small GTPases. Here, we determine whether tumor-secreted vasoactive stimulant through Rac1 inducing permeability contributes to hematogenous metastasis. Activation of Rac1 was assayed in human umbilical vein endothelial cells (HUVEC), transendothelial passages were measured by Transwell chambers, and hematogenously metastatic mouse model was generated by intravenous injection with Lewis lung carcinoma cells (LLC). LLC secreted abundant vascular endothelial growth factor (VEGF) in the culture media and sera of mice bearing LLC xenografts or metastatic LLC, and VEGF activated Rac1 through VEGF receptors/PI3Kβ signaling cascade, resulting in hyperoxidative stress and consequent hyperpermeability in HUVEC. Moreover, in co-culture of LLC and HUVEC, significant increases in endothelial permeability and transendothelial migration of LLC were robustly attenuated by either anti-VEGF neutralizing antibody or Rac1 knockdown in HUVEC. Finally, in metastatic mouse model, deletion of one copy of Rac1 in endothelium not only significantly attenuated LLC-induced vascular permeability, but robustly reduced the metastasis of LLC to lungs. This study supports that tumor-secreted vasoactive stimuli activate Rac1 to induce permeability and consequent transendothelial migration of tumor cells, and that loss of Rac1 function in endothelium is an effective therapeutic intervention for hematogenous metastasis.