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The Olsen phosphorus (Olsen-P) concentration of soil is generally a good indicator for estimating the bioavailability of P and environmental risk in soils. To maintain soil Olsen-P at adequate levels for crop growth and environmental sustainability, the relationship between soil Olsen-P and the P budget (the P input minus the output) as well as the variations of soil Olsen-P and P budget were investigated from three long-term (22 years) experiments in China. Five treatments were selected: (1) unfertilized control (CK); (2) nitrogen and potassium (NK); (3) nitrogen, phosphorous, and potassium (NPK); (4) nitrogen, phosphorous, potassium and straw; (5) nitrogen, phosphorous, potassium and manure. The results showed that without P fertilizers (CK, NK), there was a soil P deficit of 75–640 kg ha-1, and the lowest P deficit (mean of CK and NK) was in Eutric Cambisol. Soil Olsen-P decreased by 0.11–0.39 mg kg-1 year-1 in the order of Luvic Phaeozems > Eutric Cambisol > Calcaric Cambisol. Soil Olsen-P and the P deficit had a significantly (P Luvic Phaeozems > Calcaric Cambisol. Under the P fertilizer treatments (NPK, NPKS, and NPKM), soil Olsen-P showed an obvious surplus (except the NPK and NPKS in Luvic Phaeozems) of 122–2190 kg ha-1, and the largest P surplus was found under the NPKM treatment at each site. The relation between soil Olsen-P and the experimental years could be simulated using quadratic equation of one unknown in Calcaric Cambisol for the lower P input after 14 years of fertilization. And soil Olsen-P increased by 1.30–7.69 mg kg-1 year-1 in the order of Luvic Phaeozems > Eutric Cambisol. The relation between soil Olsen-P and the P surplus could be simulated by a simple linear equation except under NPK and NPKS in Luvic Phaeozems. With 100 kg ha-1 P surplus, soil Olsen-P increased by 3.24–7.27 mg kg-1 in the order of Calcaric Cambisol (6.42 mg kg-1) > Eutric Cambisol (3.24 mg kg-1). In addition, the change in soil Olsen-P with a 100 kg P ha-1 surplus (soil Olsen-P efficiency) was affected by the soil organic matter (SOM), pH, and CaCO3 content, etc. In the practice of fertilization, it’s not necessary to increase the amount of P fertilizers, farmers should take measure to solve the local problem, for adjust the soil pH of Eutric Cambisol and Calcaric Cambisol, and apply more nitrogen in Luvic Phaeozems. In the area of serious soil P surplus, it is encouraged to stop applying P fertilizers for a few years to take advantage of soil accumulated P and make the high Olsen-P content decrease to a reasonable level.

Background and objective Markov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities. Materials and methods The data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results. Results The flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively. Conclusions The flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model.

Background Currently, the prevalence of metabolic syndrome (MS) has attracted widespread public attention. However, there is a war regarding the applicability of the diagnosis in different populations regarding the distinct criteria for the diagnosis of MS. Data about the prevalence rate of MS and its components in Jiangxi Province are limited. Thus, our goals were to compare the consistency rates and applicability of three criteria, i.e., those of the International Diabetes Federation (IDF), the National Cholesterol Education Program Adult Treatment PanelⅢ (ATPⅢ), and the Chinese Diabetes Society (CDS). Methods From September 2013 to March 2014, 5959 residents (age≥18 years) from Jiangxi Province were selected by multistage stratified cluster random sampling methods. The prevalence rate of MS and its components were calculated according to the IDF, ATPⅢ and CDS criteria, and the protocols of the different criteria were measured in terms of consistency with the kappa statistic and Youden's index. Receiver operator characteristic (ROC) curve analysis was used to explore the optimal cut-off points of body mass index (BMI) and waist circumference (WC). Results The mean age of the participants was 50.52±13.92 years among the total of 5959 individuals (2451 male and 3508 female). The standardized prevalence rate of MS was 19.85%, 24.77% and 9.95% according to the IDF, ATPⅢ and CDS criteria, respectively. The order of the prevalence rates of the different components of MS according to the IDF or ATPⅢ criteria from high to low were as follows: elevated blood pressure, central obesity, reduced high density lipoprotein cholesterol (HDL-C), hyperglycemia, and hypertriglyceridemia. The most prevalent component of MS, according to the CDS criterion, was being overweight or obese, followed by elevated blood pressure, dyslipidemia and hyperglycemia. The Youden's index in IDF criterion was higher than which in CDS criterion (0.79 for IDF vs. 0.38 for CDS) referring to the ATPⅢ criterion. The agreement between the IDF and ATPⅢ criteria was good (kappa = 0.85), whereas the agreement of the CDS with the IDF and ATPⅢ criteria was moderate (kappa = 0.46 and 0.46, respectively). The ability to predict MS risk factors clusters was superior when the BMI cut-off point was 24/24kg/m2 (male/female), and the WC cut-off point was 87/80cm (male/female). Among the 18~59 years old male group, BMI was superior to WC in predicting clusters of risk factors for MS; while in the 60 years and above male group and all-age female group, WC was superior to BMI. Conclusion Our results revealed that the prevalence rate of metabolic syndrome among adults was high in Jiangxi Province. BMI and WC had different ability to predict clusters of risk factors for MS in different age groups and gender. Among the three criteria for MS, there was bigger difference in applicability for the adults of Jiangxi Province. The choice of the appropriate criteria should be based on the actual conditions of the site.

PURPOSE:Facial asymmetry often persists even after mandibular deviation corrected by the bilateral sagittal split ramus osteotomy (BSSRO) operation, since the reference facial sagittal plane for the asymmetry analysis is usually set up before the mandibular menton (Me) point correction. Our aim is to develop a predictive and quantitative method to assess the true asymmetry of the mandible after a midline correction performed by a virtual BSSRO, and to verify its availability by evaluation of the post-surgical improvement. PATIENTS AND METHODS:A retrospective cohort study was conducted at the Hospital of Stomatology, Sun Yat-sen University (China) of patients with pure hemi-mandibular elongation (HE) from September 2010 through May 2014. Mandibular models were reconstructed from CBCT images of patients with pre-surgical orthodontic treatment. After mandibular de-rotation and midline alignment with virtual BSSRO, the elongation hemi-mandible was virtually mirrored along the facial sagittal plane. The residual asymmetry, defined as the superimposition and boolean operation of the mirrored elongation side on the normal side, was calculated, including the volumetric differences and the length of transversal and vertical asymmetry discrepancy. For more specific evaluation, both sides of the hemi-mandible were divided into the symphysis and parasymphysis (SP), mandibular body (MB), and mandibular angle (MA) regions. Other clinical variables include deviation of Me point, dental midline and molar relationship. The measurement of volumetric discrepancy between the two sides of post-surgical hemi-mandible were also calculated to verify the availability of virtual surgery. Paired t-tests were computed and the P value was set at .05. RESULTS:This study included 45 patients. The volume differences were 407.8±64.8 mm3, 2139.1±72.5 mm3, and 422.5±36.9 mm3; residual average transversal discrepancy, 1.9 mm, 1.0 mm, and 2.2 mm; average vertical discrepancy, 1.1 mm, 2.2 mm, and 2.2 mm (before virtual surgery). The post-surgical volumetric measurement showed no statistical differences between bilateral mandibular regions. CONCLUSIONS:Mandibular asymmetry persists after Me point correction. A 3D quantification of mandibular residual asymmetry after Me point correction and mandible de-rotation with virtual BSSRO sets up a true reference mirror plane for comprehensive asymmetry assessment of bilateral mandibular structure, thereby providing an accurate guidance for orthognathic surgical planning.

Long-term manure application is recognized as an efficient management practice to enhance soil organic carbon (SOC) accumulation and nitrogen (N) mineralization capacity. A field study was established in 1979 to understand the impact of long-term manure and/or chemical fertilizer application on soil fertility in a continuous maize cropping system. Soil samples were collected from field plots in 2012 from 9 fertilization treatments (M0CK, M0N, M0NPK, M30CK, M30N, M30NPK, M60CK, M60N, and M60NPK) where M0, M30, and M60 refer to manure applied at rates of 0, 30, and 60 t ha(-1) yr(-1), respectively; CK indicates no fertilizer; N and NPK refer to chemical fertilizer in the forms of either N or N plus phosphorus (P) and potassium (K). Soils were separated into three particle-size fractions (2000-250, 250-53, and 250-53 μm > 53 μm fraction, whereas the amount of C and N mineralization followed the reverse order. In the

Non-viral gene delivery system with many advantages has a great potential for the future of gene therapy. One inherent obstacle of such approach is the uptake by endocytosis into vesicular compartments. Receptor-mediated gene delivery method holds promise to overcome this obstacle. In this study, we developed a receptor-mediated gene delivery system based on a combination of the Pseudomonas exotoxin A (PE), which has a receptor binding and membrane translocation domain, and the hyperthermophilic archaeal histone (HPhA), which has the DNA binding ability. First, we constructed and expressed the rPE-HPhA fusion protein. We then examined the cytotoxicity and the DNA binding ability of rPE-HPhA. We further assessed the efficiency of transfection of the pEGF-C1 plasmid DNA to CHO cells by the rPE-HPhA system, in comparison to the cationic liposome method. The results showed that the transfection efficiency of rPE-HPhA was higher than that of cationic liposomes. In addition, the rPE-HPhA gene delivery system is non-specific to DNA sequence, topology or targeted cell type. Thus, the rPE-HPhA system can be used for delivering genes of interest into mammalian cells and has great potential to be applied for gene therapy.

Objective Pain management is a huge challenge in the treatment of rheumatoid arthritis (RA), and central sensitization is reportedly involved in the development of pain. The current study was undertaken to explore the possible role of N-methyl-D-aspartate receptors (NMDARs) in the spinal mechanism of central sensitization in RA using a collagen-induced arthritis (CIA) model. Methods Mechanical hypersensitivity was assessed in C57BL/6 mice, before and after the induction of CIA via administration of chick type II collagen. Analgesic drugs, receptor antagonist, and kinase inhibitor were administrated intrathecally in the spinal cord. Protein expression and phosphorylation changes were detected via immunoblotting. Results CIA mice developed significant mechanical hypersensitivity, and spinal administration of the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (D-APV) effectively attenuated peripheral pain hypersensitivity. There was specific enhancement of synaptic NR2B-containing NMDAR (NR2BR) expression in the spinal dorsal horns of the mice. Both the increased total protein expression of NR2B subunit and the enhanced total phosphorylation level of NR2B subunit at 1472 tyrosine promoted the synaptic expression of NMDAR in the mice. Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472. Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol. Conclusion Specific enhancement of NR2BR in the spinal dorsal horn may be vital for central sensitization in the CIA model of RA. The NR2BR/ERK2 pathway may be a promising target for pain management in RA patients.

On 20 June 2015, a cholera outbreak affecting more than 30 people was reported in a fishing village, Katwe, in Kasese District, south-western Uganda. We investigated this outbreak to identify the mode of transmission and to recommend control measures. We defined a suspected case as onset of acute watery diarrhoea between 1 June and 15 July 2015 in a resident of Katwe village; a confirmed case was a suspected case with Vibrio cholerae cultured from stool. For case finding, we reviewed medical records and actively searched for cases in the community. In a case-control investigation we compared exposure histories of 32 suspected case-persons and 128 age-matched controls. We also conducted an environmental assessment on how the exposures had occurred. We found 61 suspected cases (attack rate = 4.9/1000) during this outbreak, of which eight were confirmed. The primary case-person had onset on 16 June; afterwards cases sharply increased, peaked on 19 June, and rapidly declined afterwards. After 22 June, eight scattered cases occurred. The case-control investigation showed that 97% (31/32) of cases and 62% (79/128) of controls usually collected water from inside a water-collection site "X" (ORM-H = 16; 95% CI = 2.4-107). The primary case-person who developed symptoms while fishing, reportedly came ashore in the early morning hours on 17 June, and defecated "near" water-collection site X. We concluded that this cholera outbreak was caused by drinking lake water collected from inside the lakeshore water-collection site X. At our recommendations, the village administration provided water chlorination tablets to the villagers, issued water boiling advisory to the villagers, rigorously disinfected all patients' faeces and, three weeks later, fixed the tap-water system.

Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ(+)CD3(+) T cells and IL-17(+)CD4(+) T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus.

PurposeTo evaluate prevalence and associated factors for myopia in high school students in Beijing.MethodsGrade 10 and 11 high school students were randomly selected from nine randomly selected districts of Beijing. The students underwent non-cylcoplegic auto-refractometry and an interview.ResultsOut of 4798 eligible students, 4677 (93.4%) students (mean age:16.9±0.7years;range:16-18 years) participated. Mean refractive error of right eyes and left eyes was -2.78±2.29 diopters and -2.59±2.50 diopters, respectively. Prevalence of myopia (defined as ≤ -1.00 diopters in the worse eye) was 80.7% (95% Confidence Interval (CI): 79.6-81.8%). Out of 3773 students with myopia, 1525 (40.4%) wore glasses daily. In multiple logistic regression analysis, a higher prevalence of myopia was associated with female sex (odds ratio (OR) = 1.31;95%CI:1.11-1.55), Han ethnicity (OR = 1.64;95%CI:1.28-2.11), attending key schools (OR = 1.48;95%CI:1.24,1.77), higher family income (OR = 1.37;95%CI:1.09-1.71), longer time spent for near work (OR = 1.43;95%CI:1.06-1.93), shorter near work distance (OR = 1.87;95%CI:1.55-2.26), lower frequency of active rest during studying (OR = 1.40;95%CI:1.16-1.70), and parental myopia (OR = 2.28;95%CI:1.80-2.87). The interaction between distance from near work and time spent for near work was statistically (P = 0.03) significant. In multiple logistic regression analysis, higher prevalence of high myopia (≤-6.0 diopters) was associated with studying in key schools (OR = 1.38;95%CI:1.05,1.81), lower frequency of active rest during studying (OR = 1.40;95%CI:1.09,1.79), and a higher number of myopic parents (OR = 2.66;95%CI:2.08,3.40).ConclusionsA prevalence of about 80% for myopia and a prevalence of about 10% for high myopia in students aged 16 to 18 years and attending classes of grade 10 and 11 in a Chinese metropolitan region is another example of the high prevalence of moderate and high myopia in metropolitan areas of China. With this young myopic generation getting older, myopia as cause for visual impairment and blindness may further increase in importance. Future studies may address whether active rests during studying with looking into the distance are preventive against myopia development or progression.

Purpose To introduce a practical method of subretinal injection in mice and evaluate injection-induced retinal detachment (RD) and damage using a dynamic imaging system, electrophysiology, and histology. Methods After full dilation of a 2-month-old C57BL/6J mouse pupil, the cornea near the limbus was punctured with a 30 ½-gague disposable beveled needle. A 33 ½-gauge blunt needle was inserted through the corneal perforation into the anterior chamber, avoiding the lens before going deeper into the vitreous cavity, and penetrating the inner retina to reach the subretinal space. The mice were divided into four groups: in group 1, about 80–100% of the retina was filled with subretinally injected solution; in group 2, approximately 50–70% of the retina was filled with injected solution; in group 3, the procedures were stopped before solution injection; and non-injected eyes were used as the negative control in group 4. An optical coherence tomography (OCT) imaging system was used to monitor retinal reattachment during the first three days following the injections. Histological and functional changes were examined by light microscopy and electroretinography (ERG) at five weeks post-injection. Results After a short-term training, a 70% success rate with 50% or more coverage (i.e., retinal blebs occupied 50% or more retinal area and filled with the injected solution) with minimal injection-related damages can be achieved. Bleb formation was associated with retinal detachment (RD) between the neuroretina and the retinal pigment epithelium (RPE) layer. Partial RD could be observed at post-injection day 1, and by day 2 most of the retina had reattached. At 5 weeks post-injection, compared to uninjected control group 4, the b-wave amplitudes of ERG decreased 22% in group 1, 16% in group 2, and 7% in group 3; the b-wave amplitudes were statistically different between the uninjected group and the groups with either 50–70% or 80–100% coverage. The subretinal injection-induced RD reattached and became stable at five weeks post-injection, although some photoreceptor damage could still be observed in and around the injection sites, especially in 80–100% coverage group. Conclusions Trans-corneal subretinal injection is effective and practical, although subretinal injection-related damages can cause some morphological and functional loss.

The Olsen phosphorus (P) concentration of a soil is a key index that can be used to evaluate the P supply capacity of the soil and to estimate the optimal P fertilization rate. A study of the relationship between the soil Olsen P concentration and the P balance (P input minus P output) and their variations among different fertilization patterns will help to provide useful information for proper management of P fertilization. In this paper, the two investigated long-term experiments were established on black soils in the northeast region of China. Six fertilization treatments were selected: (1) unfertilized (CK); (2) nitrogen only (N); (3) nitrogen and potassium (NK); (4) nitrogen and phosphorus (NP); (5) nitrogen, phosphorus, and potassium (NPK); and (6) nitrogen, phosphorus, potassium and manure (NPKM). The results showed that the average Olsen P concentrations in the black soils at Gongzhuling and Harbin (16- and 31-year study periods, respectively), decreased by 0.49 and 0.56 mg kg-1 a-1, respectively, without P addition and increased by 3.17 and 1.78 mg kg-1 a-1, respectively, with P fertilization. The changes in soil Olsen P concentrations were significantly (P

Human APOBEC3G (hA3G) is a cytidine deaminase that restricts replication of certain viruses. We have previously reported that hA3G was a host restriction factor against hepatitis C virus (HCV) replication, and hA3G stabilizers showed a significant inhibitory activity against HCV. However, the molecular mechanism of hA3G against HCV remains unknown. We show in this study that hA3G’s C-terminal directly binds HCV non-structural protein NS3 at its C-terminus, which is responsible for NS3’s helicase and NTPase activity. Binding of hA3G to the C-terminus of NS3 reduced helicase activity, and therefore inhibited HCV replication. The anti-HCV mechanism of hA3G appeared to be independent of its deamination activity. Although early stage HCV infection resulted in an increase in host hA3G as an intracellular response against HCV replication, hA3G was gradually diminished after a long-term incubation, suggesting an unknown mechanism(s) that protects HCV NS3 from inactivation by hA3G. The process represents, at least partially, a cellular defensive mechanism against HCV and the action is mediated through a direct interaction between host hA3G and HCV NS3. We believe that understanding of the antiviral mechanism of hA3G against HCV might open an interesting avenue to explore hA3G stabilizers as a new class of anti-HCV agents.

Objective C-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, whereas its role in coronary artery disease (CAD) has not been clarified, especially in diabetics with differing body mass indices (BMIs). Design and Methods This cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese) based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group. Results The patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C) and lower estimated glomerular filtration rate (eGFR). Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005), insulin treatment (OR=1.832, p=0.027) hypertension (OR=1.987, p=0.016) and hyperlipidemia (OR=4.159, p

The phosphorus activation coefficient (PAC, the ratio of available P to total P) is an important indicator of soil P availability and the transformation of P fractions. Understanding the details of the PAC is useful to estimate soil available P status and to provide P management guidance. In this research, soils from five long-term (23 years) fertilization treatments in three croplands were selected to examine the relationships between the PAC and P fractions and to analyse the influencing factors. PAC was affected by both soil types and fertilization treatments. Compared to the unfertilized control (CK) treatment, long-term P application significantly increased the PAC, all of the inorganic P (Pi) fractions and most of the organic P (Po) fractions in all the three soils, particularly in chemical fertilizer combined with manure treatment (NPKM). The PAC was significantly correlated to all of the Pi fractions proportions (P

Recent spatiotemporal report demonstrated that epidermal stem cells have equal potential to divide or differentiate, with no asymmetric cell division observed. Therefore, how epithelial stem cells maintain lifelong stem-cell support still needs to be elucidated. In mouse blood and bone marrow, we found a group of large cells stained strongly for eosin and containing coiled-tubing-like structures. Many were tightly attached to each other to form large cellular clumps. After sectioning, these large cell-clumps were composed of not cells but numerous small particles, however with few small "naked" nuclei. The small particles were about 2 to 3 μm in diameter and stained dense red for eosin, so they may be rich in proteins. Besides the clumps composed of small particles, we identified clumps formed by fusion of the small particles and clumps of newly formed nucleated cells. These observations suggest that these small particles further fused and underwent cellularization. E-cadherin was expressed in particle-fusion areas, some "naked" nuclei and the newly formed nucleated cells, which suggests that these particles can form epithelial cells via fusion and nuclear remodeling. In addition, we observed similar-particle fusion before epithelial cellularization in mouse kidney ducts after kidney ischemia, which suggests that these particles can be released in the blood and carried to the target tissues for epithelial-cell regeneration. Oct4 and E-cadherin expressed in the cytoplasmic areas in cells that were rich in protein and mainly located in the center of the cellular clumps, suggesting that these newly formed cells have become tissue-specific epithelial stem cells. Our data provide evidence that these large particle-producing cells are the origin of epithelial stem cells. The epithelial stem cells are newly formed by particle fusion.

Hemocyanins (Hcs) of arthropods and mollusks function not only as oxygen transporters, but also as phenoloxidases (POs). In invertebrates, PO is an important component in the innate immune cascade, where it functions as the initiator of melanin synthesis, a pigment involved in encapsulating and killing of pathogenic microbes. Although structures of Hc from several species of invertebrates have been reported, the structural basis for how PO activity is triggered by structural changes of Hc in vivo remains poorly understood. Here, we report a 6.8 A cryo-electron microscopy (cryo-EM) structure of the isomeric form of hemocyanin, which was isolated from Abalone Shriveling syndrome-associated Virus (AbSV) infected abalone (Halitotis diversicolor), and build a pseudoatomic model of isomeric H. diversicolor hemocyanin 1 (HdH1). Our results show that, compared with native form of HdH1, the architecture of isomeric HdH1 turns into a more relaxed form. The interactions between certain functional units (FUs) present in the native form of Hc either decreased or were totally abolished in the isomeric form of Hc. As a result of that, native state Hc switches to its isomeric form, enabling it to play its role in innate immune responses against invading pathogens.

Previous studies mostly investigate player's cooperative behavior as affected by game time-scale or individual diversity. In this paper, by involving both time-scale and diversity simultaneously, we explore the effect of stochastic heterogeneous interaction. In our model, the occurrence of game interaction between each pair of linked player obeys a random probability, which is further described by certain distributions. Simulations on a 4-neighbor square lattice show that the cooperation level is remarkably promoted when stochastic heterogeneous interaction is considered. The results are then explained by investigating the mean payoffs, the mean boundary payoffs and the transition probabilities between cooperators and defectors. We also show some typical snapshots and evolution time series of the system. Finally, the 8-neighbor square lattice and BA scale-free network results indicate that the stochastic heterogeneous interaction can be robust against different network topologies. Our work may sharpen the understanding of the joint effect of game time-scale and individual diversity on spatial games.

Dysfunction of renin-angiotensin system (RAS) contributes to the pathogenesis of diabetic retinopathy (DR). Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (pro) renin receptor ((P)RR). Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (P) RR blocker handle-region peptide (HRP) on diabetic retinopathy in streptozotocin (STZ)-induced diabetic transgenic (mRen2)27 rats (a model with high plasma prorenin levels) as well as prorenin stimulated cytokine expression in cultured Muller cells. Adult (mRen2)27 rats were randomly divided into the following groups: (1) non-diabetic; (2) diabetic treated with vehicle; (3) diabetic treated with aliskiren (10 mg/kg per day); and (4) diabetic treated with aliskiren+HRP (1 mg/kg per day). Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen2)27 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen2)27 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Muller cells, prorenin significantly increased the expression levels of IL-1 alpha and TNF-alpha, and this was completely blocked by aliskiren or HRP, their combination, (P)RR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (P)RR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular effects of prorenin in vitro, argue against the combined application of (P)RR blockade and renin inhibition in diabetic retinopathy.

Background Multilocus PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) is a new strategy for pathogen identification, but information about its application in fungal identification remains sparse. Methods One-hundred and twelve strains and isolates of clinically important fungi and Prototheca species were subjected to both rRNA gene sequencing and PCR/ESI-MS. Three regions of the rRNA gene were used as targets for sequencing: the 5′ end of the large subunit rRNA gene (D1/D2 region), and the internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions). Microbial identification (Micro ID), acquired by combining results of phenotypic methods and rRNA gene sequencing, was used to evaluate the results of PCR/ESI-MS. Results For identification of yeasts and filamentous fungi, combined sequencing of the three regions had the best performance (species-level identification rate of 93.8% and 81.8% respectively). The highest species-level identification rate was achieved by sequencing of D1/D2 for yeasts (92.2%) and ITS2 for filamentous fungi (75.8%). The two Prototheca species could be identified to species level by D1/D2 sequencing but not by ITS1 or ITS2. For the 102 strains and isolates within the coverage of PCR/ESI-MS identification, 87.3% (89/102) achieved species-level identification, 100% (89/89) of which were concordant to Micro ID on species/complex level. The species-level identification rates for yeasts and filamentous fungi were 93.9% (62/66) and 75% (27/36) respectively. Conclusions rRNA gene sequencing provides accurate identification information, with the best results obtained by a combination of ITS1, ITS2 and D1/D2 sequencing. Our preliminary data indicated that PCR/ESI-MS method also provides a rapid and accurate identification for many clinical relevant fungi.

ObjectiveTo identify the risk factors and source of infection leading to human infections with the Influenza A(H7N9) virus in urban and rural areas.MethodsWe conducted a case-control investigation to identify potential exposures and risk factors. Controls were randomly selected from the same community as the cases using random digit dialing. We used exact conditional logistic regression to evaluate the exposures and risk factors, stratified by urban and rural residence.ResultsBuying live or freshly slaughtered poultry from a market was significantly associated with illness onset among both urban [48% of 25 case-patients and 12% of 125 control-persons, adjusted odds ratio (AOR) = 19, 95% CI: 2.3-929] and rural (33% of 18 case-patients and 8.9% of 90 control-persons, AOR = 13, 95% CI:1.5-∞) residents. In rural area, tending to home-raised poultry (56% of 18 case-patients and 10% of 90 control-persons, AOR = 57, 95% CI: 7.5-∞) and existence of a poultry farm in the vicinity of the residence (28% of 18 case-patients and 5.6% of 90 control-persons, AOR = 37, 95% CI: 3.8-∞) were also significantly associated with disease onset. Presence of underlying medical conditions was a significant risk factor for urban residents (76% of 25 case-patients and 13% of 125 control-persons, AOR = 49, 95% CI: 7.1-2132).ConclusionsBuying live or freshly slaughtered poultry from a market is a risk factor for both urban and rural residents, tending to home-raised poultry and existence of a poultry farm in the vicinity of the residence are risk factors unique for rural residents. The virus might have been in stealth circulation in the poultry population before infecting humans. We recommend strict poultry market management and multisectoral collaboration to identify the extent of poultry infection in China.

Background The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis. Objective To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population. Methods In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays. Results In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2-4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49-0.90). Conclusions Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.

Arthroscopic lavage and arthrocentesis, performed with different inner-diameter lavage needles, are the current minimally invasive techniques used in temporomandibular joint disc displacement (TMJ-DD) for pain reduction and functional improvement. In the current study, we aimed to explore the biomechanical influence and explain the diverse clinical outcomes of these two approaches with computational fluid dynamics. Data was retrospectively analyzed from 78 cases that had undergone arthroscopic lavage or arthrocentesis for TMJ-DD from 2002 to 2010. Four types of finite volume models, featuring irrigation needles of different diameters, were constructed based on computed tomography images. We investigated the flow pattern and pressure distribution of lavage fluid secondary to caliber-varying needles. Our results demonstrated that the size of outflow portal was the critical factor in determining irrigated flow rate, with a larger inflow portal and a smaller outflow portal leading to higher intra-articular pressure. This was consistent with clinical data suggesting that increasing the mouth opening and maximal contra-lateral movement led to better outcomes following arthroscopic lavage. The findings of this study could be useful for choosing the lavage apparatus according to the main complaint of pain, or limited mouth opening, and examination of joint movements.

Fixed vestibular appliances decrease the "self-cleansing" action of saliva and promote aggregation of dental plaque by disturbing the salivary flow field on tooth surfaces, leading to a higher prevalence of enamel demineralization and periodontal diseases. In the current study, we investigated the salivary dynamic characteristics of plaque retention and periodontal status around appliances during orthodontic treatment. By reconstructing lower central incisors and orthodontic appliances, we simulated saliva flow on the tooth surface and then characterized and quantified the salivary flow pattern surrounding the bracket and archwire. In parallel, we tested the total peri-bracket bacterial counts and periodontal status to assess interrelations. Our results demonstrate that orthodontic appliances disturb the salivary flow field on tooth surfaces and can lead to a decrease in salivary velocity and an increase in bacterial numbers. Local vortexes forming in the areas gingival to the bracket, together with the narrow space limitation, contributed to the periodontal inflammatory response. This study confirms that changes in salivary flow are an obvious predisposing factor for bacterial accumulation, and advances the ability to replicate, in vitro, the salivary characteristics of plaque retention and periodontal status around appliances during orthodontic treatment.

OBJECTIVES: To quantitatively analyze placental perfusion in a rat model at different gestation time and different portions of placenta by real-time contrast-enhanced ultrasound (CEUS) and parametric imaging analysis. MATERIALS AND METHODS: Sixty pregnant rats at different gestation time (15 dys,17 days and 20 days) were injected intravenously with microbubbles (5×10(5) microbubbles /ml, 1.0 ml/kg), and cadence contrast pulse sequencing (transmission frequency of 7 MHz, mechanical index 0.18) was performed. Dynamic enhancement changes in placenta at different gestation time and different portions of placenta were measured and enhancement parameters analyzed with software. Correlation between enhancement parameters and average area densities of placenta vascular compartment was compared. RESULTS: The pattern and real-time sequence of enhancement in uterus and placenta were clearly depicted by CEUS. The time-to-peak enhancement was earlier in central portion than that in peripheral portion (12.30±6.33s vs 36.26±10.65 s, p = 0.005), and peak intensity of enhancement is much higher in central portion than that in peripheral portion (30.20±2.85 dB vs 20.95±6.25 dB, p = 0.000). The peak intensity of enhancement at day 15 (27.70±4.47 dB) was lower than that at day 17 (30.20±2.85 dB, p = 0.042) and at day 20 (31.85±4.41 dB, p = 0.015) of gestation. Significant correlation between average area densities of vascular compartment and the peak intensity of enhancement was identified in placenta at different gestation time (p

Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.