Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia.

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

Reducing postoperative hypothermia in infants: Quality improvement in China.

BACKGROUND: Unintended postoperative hypothermia in infants is associated with increased mortality and morbidity. We noted consistent hypothermia postoperatively in more than 60% of our neonatal intensive care (NICU) babies. Therefore, we set out to determine whether a targeted quality improvement (QI) project could decrease postoperative hypothermia rates in infants. OBJECTIVES: Our SMART aim was to reduce postoperative hypothermia (<36.5°C) in infants from 60% to 40% within 6 months. METHODS: This project was approved by IRB at Guangzhou Women and Children's Medical Center, China. The QI team included multidisciplinary healthcare providers in China and QI experts from Children's Hospital of Philadelphia, USA. The plan-do-study-act (PDSA) cycles included establishing a perioperative-thermoregulation protocol, optimizing the transfer process, and staff education. The primary outcome and balancing measures were, respectively, postoperative hypothermia and hyperthermia (axillary temperature < 36.5°C, >37.5°C). Data collected was analyzed using control charts. The factors associated with a reduction in hypothermia were explored using regression analysis. RESULTS: There were 295 infants in the project. The percentage of postoperative hypothermia decreased from 60% to 37% over 26 weeks, a special cause variation below the mean on the statistical process control chart. Reduction in hypothermia was associated with an odds of 0.17 (95% CI: 0.06-0.46; p <.001) for compliance with the transport incubator and 0.24 (95% CI: 0.1-0.58; p =.002) for prewarming the OR ambient temperature to 26°C. Two infants had hyperthermia. CONCLUSIONS: Our QI project reduced postoperative hypothermia without incurring hyperthermia through multidisciplinary team collaboration with the guidance of QI experts from the USA.

From electronic structure to model application for alkyl cyclohexane combustion chemistry: H-atom abstraction reactions by HȮ2 radical.

Chemical kinetic studies of hydrogen atom abstraction reactions by hydroperoxyl (HȮ2) radical from six alkyl cyclohexanes of methyl cyclohexane (MCH), ethyl cyclohexane (ECH), n-propyl cyclohexane (nPCH), iso-propyl cyclohexane (iPCH), sec-butyl cyclohexane (sBCH), and iso-butyl cyclohexane (iBCH) are carried out systematically through high-level ab initio calculations. Geometry optimizations and frequency calculations for all species involved in the reactions are performed at the M06-2X/6-311++G(d,p) level of theory. Electronic single-point energy calculations are calculated at the UCCSD(T)-F12a/cc-pVDZ-F12 level of theory, with zero-point energy corrections. High-pressure limit rate constants for the reactions of alkyl cyclohexanes + HȮ2, in the temperature range of 500-2000 K, are calculated using conventional transition state theory taking asymmetric Eckart tunneling corrections and the one-dimensional hindered rotor approximation into consideration. Elementary reaction rate constants and branching ratios for each alkyl cyclohexane species were investigated, and rate constant rules of primary, secondary, and tertiary sites on the side-chain and the ring are provided here. Additionally, temperature-dependent thermochemical properties for reactants and products were also obtained in this work. The updated kinetics and thermochemistry data are used in the alkyl cyclohexane mechanisms to investigate their effects on ignition delay time predictions of shock tube and rapid compression machine data, and species concentrations from a jet-stirred reactor. It is found that these investigated reactions promote ignition delay times in the temperature range of 800-1200 K and also improve the prediction of cyclic olefin species formation which stems from the decomposition of fuel radicals.

[Effect of strontium in drinking water on blood pressure and inflammatory function in hypertension mice].

OBJECTIVE: To explore the effect of strontium in drinking water on blood pressure in hypertensive mice and its possible mechanism. METHODS: Establishment of mouse model of high blood pressure by drinking 2 mg/mL N'nitro-L-arginine methyl eater hydrochloride(L-NAME) for 4 weeks. One hundred ICR mice were randomly divided into normal control group(n=20) and model group(n=80) according to systolic blood pressure. Eighty hypertensive mice were randomly divided into model control group(n=20), 2.5 mg/L strontium water group(n=20), 5.0 mg/L strontium water group(n=20) and 10.0 mg/L strontium water group(n=20). The body weight and blood pressure of mice were measured every week. After 10 weeks, serum sodium(Na), potassium(K), calcium(Ca), magnesium(Mg), Chlorine(Cl), nitric oxide(NO), renin, angiotensin II(Ang II), aldosterone(ALD), endothelial nitric oxide synthase(eNOS), intercellular cell adhesion molecule-1(ICAM-1), heart interleukin-6(IL-6), interleukin-1 beta(IL-1ß) and tumor necrosis factor-α(TNF-α) were determined. RESULTS: After 10 weeks of intervention, the systolic blood pressure in the low, medium and high strontium water groups(129.60±4.90 mmHg vs.127.33±6.35 mmHg vs.124.70±3.91 mmHg) was significantly lower than that of the model control group(141.84±5.34 mmHg)(P<0.05). The diastolic blood pressure in the high strontium water group(84.74±5.49 mmHg) was significantly lower than that of the model control group(92.21±10.08 mmHg). The contents of serum potassium, calcium and magnesium in medium strontium gourp(8.06±0.80 mmol/L vs.2.34±0.13 mmol/L vs.0.57±0.12 mmol/L) and high strontium group(9.59±0.58 mmol/L vs. 2.37±0.17 mmol/L vs.0.58±0.09 mmol/L) were significantly higher than those in normal control group(6.64±0.57 mmol/L vs.2.07±0.15 mmol/L vs.0.46±0.10 mmol/L) and model control group(6.62±0.53 mmol/L vs.2.09±0.11 mmol/L vs.0.48±0.09 mmol/L)(P<0.05). Compared with model control group, the contents of renin(24.08±6.65 ng/mL vs.15.24±3.88 ng/mL), AngII(263.30±61.66 pg/mL vs.203.31±54.95 pg/mL), ALD(102.41±22.39 pg/mL vs. 60.31±10.83 pg/mL), ICAM-1(367.17±120.08 ng/mL vs.224.45±46.86 ng/mL), IL-6(5.90±0.66 ng/mL vs.3.88±1.08 ng/mL), IL-1ß(6.37±1.83 ng/mL vs.3.44±1.28 ng/mL) and TNF-α(9.35±1.41 ng/mL vs.5.68±2.11 ng/mL) in high strontium group were significantly decreased(P<0.05). CONCLUSION: Strontium can reduce the blood pressure of hypertensive mice by regulating the eNOS/NO pathway and reducing the production of inflammatory factors.

Development of a fan-beam TDLAS-based tomographic sensor for rapid imaging of temperature and gas concentration.

This work aims to develop a fan-beam tomographic sensor using tunable diode lasers that can simultaneously image temperature and gas concentration with both high spatial and temporal resolutions. The sensor features three key advantages. First, the sensor bases on a stationary fan-beam arrangement, by which a high spatial resolution is guaranteed because the distance between two neighboring detectors in a view is approximately reduced to the size of a photodiode. Second, fan-beam illumination from five views is simultaneously generated instead of rotating either the fanned beams or the target, which significantly enhances the temporal resolution. Third, a novel set of optics with the combination of anamorphic prism pair and cylindrical lens is designed, which greatly improves the uniformity of the planar beams, and hence improves the reconstruction fidelity. This paper reports the tomographic model, optics design, numerical simulation and experimental validation of the sensor. The sensor exhibits good applicability for flame monitoring and combustion diagnosis.

Irrelevance of USF2 rs916145 polymorphism with the risk of biliary atresia susceptibility in Southern Chinese children.

BACKGROUNDS: Biliary atresia (BA) is a very rare neonatal disease, however, it has been the most common cause of obstructive jaundice in infancy. The complex pathogenesis of BA is not entirely clear and a lot of possible pathogenic mechanisms have been proposed to explain the etiology of BA, including genetic, inflammatory, environmental and developmental abnormalities. As a transcription factor, USF2 gene rs916145 polymorphism has been shown to be related to the risk of BA. METHODS: We examined the USF2 rs916145 genotype in a large case-control study consisting of 506 BA patients and 1473 healthy controls, using the MassARRAY iPLEX Gold system (Sequenom). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the USF2 gene rs916145 polymorphism and BA susceptibility. RESULTS: The frequency of different genotypes showed no statistical significance (GG/GC, OR: 1.09, P=0.470, 95% CI: 0.87-1.35; GG/CC, OR: 0.86, P=0.378, 95% CI: 0.62-1.20). No obvious association was revealed between the USF2 gene rs916145 polymorphism and BA susceptibility. CONCLUSION: USF2 rs916145 polymorphism may not be the best predictor of BA.

Metabolite signatures of diverse Camellia sinensis tea populations.

The tea plant (Camellia sinensis) presents an excellent system to study evolution and diversification of the numerous classes, types and variable contents of specialized metabolites. Here, we investigate the relationship among C. sinensis phylogenetic groups and specialized metabolites using transcriptomic and metabolomic data on the fresh leaves collected from 136 representative tea accessions in China. We obtain 925,854 high-quality single-nucleotide polymorphisms (SNPs) enabling the refined grouping of the sampled tea accessions into five major clades. Untargeted metabolomic analyses detect 129 and 199 annotated metabolites that are differentially accumulated in different tea groups in positive and negative ionization modes, respectively. Each phylogenetic group contains signature metabolites. In particular, CSA tea accessions are featured with high accumulation of diverse classes of flavonoid compounds, such as flavanols, flavonol mono-/di-glycosides, proanthocyanidin dimers, and phenolic acids. Our results provide insights into the genetic and metabolite diversity and are useful for accelerated tea plant breeding.

Defensive Responses of Tea Plants (Camellia sinensis) Against Tea Green Leafhopper Attack: A Multi-Omics Study.

Tea green leafhopper [Empoasca (Matsumurasca) onukii Matsuda] is one of the most devastating pests of tea plants (Camellia sinensis), greatly impacting tea yield and quality. A thorough understanding of the interactions between the tea green leafhopper and the tea plant would facilitate a better pest management. To gain more insights into the molecular and biochemical mechanisms behind their interactions, a combined analysis of the global transcriptome and metabolome reconfiguration of the tea plant challenged with tea green leafhoppers was performed for the first time, complemented with phytohormone analysis. Non-targeted metabolomics analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS), together with quantifications by ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QqQ MS), revealed a marked accumulation of various flavonoid compounds and glycosidically bound volatiles but a great reduction in the level of amino acids and glutathione upon leaf herbivory. RNA-Seq data analysis showed a clear modulation of processes related to plant defense. Genes pertaining to the biosynthesis of phenylpropanoids and flavonoids, plant-pathogen interactions, and the biosynthesis of cuticle wax were significantly up-regulated. In particular, the transcript level for a CER1 homolog involved in cuticular wax alkane formation was most drastically elevated and an increase in C29 alkane levels in tea leaf waxes was observed. The tea green leafhopper attack triggered a significant increase in salicylic acid (SA) and a minor increase in jasmonic acid (JA) in infested tea leaves. Moreover, transcription factors (TFs) constitute a large portion of differentially expressed genes, with several TFs families likely involved in SA and JA signaling being significantly induced by tea green leafhopper feeding. This study presents a valuable resource for uncovering insect-induced genes and metabolites, which can potentially be used to enhance insect resistance in tea plants.

Tunable diode laser absorption spectroscopy-based tomography system for on-line monitoring of two-dimensional distributions of temperature and H2O mole fraction.

To monitor two-dimensional (2D) distributions of temperature and H2O mole fraction, an on-line tomography system based on tunable diode laser absorption spectroscopy (TDLAS) was developed. To the best of the authors' knowledge, this is the first report on a multi-view TDLAS-based system for simultaneous tomographic visualization of temperature and H2O mole fraction in real time. The system consists of two distributed feedback (DFB) laser diodes, a tomographic sensor, electronic circuits, and a computer. The central frequencies of the two DFB laser diodes are at 7444.36 cm(-1) (1343.3 nm) and 7185.6 cm(-1) (1391.67 nm), respectively. The tomographic sensor is used to generate fan-beam illumination from five views and to produce 60 ray measurements. The electronic circuits not only provide stable temperature and precise current controlling signals for the laser diodes but also can accurately sample the transmitted laser intensities and extract integrated absorbances in real time. Finally, the integrated absorbances are transferred to the computer, in which the 2D distributions of temperature and H2O mole fraction are reconstructed by using a modified Landweber algorithm. In the experiments, the TDLAS-based tomography system was validated by using asymmetric premixed flames with fixed and time-varying equivalent ratios, respectively. The results demonstrate that the system is able to reconstruct the profiles of the 2D distributions of temperature and H2O mole fraction of the flame and effectively capture the dynamics of the combustion process, which exhibits good potential for flame monitoring and on-line combustion diagnosis.

Associations Between Sleep Quality and Migraine Frequency: A Cross-Sectional Case-Control Study.

Migraine has been associated with sleep disturbances. Relationship between sleep quality and migraine frequency is yet to be determined. The present study aimed to investigate sleep disturbances among low-frequency, moderate-frequency, high-frequency, and chronic migraineurs, with and without auras, with well-controlled confounding variables.This cross-sectional controlled study included 357 subjects from an outpatient headache clinic in Taiwan. Standardized questionnaires were utilized to collect demographic, migraine, sleep, depression, anxiety, and restless leg syndrome characteristics in all participants. According to frequency of migraine attacks, patients were divided into 4 groups: with 1 to 4 migraine days per month, 5 to 8 migraine days in a month, 9 to 14 migraine days in a month, and >14 migraine days per month. The Pittsburgh Sleep Quality Index (PSQI) and subgroup items were used to evaluate sleep quality. The association between migraine frequency and sleep quality was investigated using multivariable linear regression and logistic regression.The PSQI total score was highest in patients with high frequent migraine (10.0 ±â€Š3.4) and lowest in controls (7.0 ±â€Š3.4) with a significant trend analysis (P for trend = 0.006). Migraine frequency had an independent effect on the items "Cannot get to sleep within 30 minutes" (P < 0.001), "Wake up in the middle of the night or early morning" (P < 0.001), "Bad dreams" (P = 0.001), "Pain" (P = 0.004), and "Quality of sleep" (P < 0.001). The result showed the effect of migraine frequency in both the aura-present (P for trend = 0.008) and the aura-absent subgroups (P for trend = 0.011).High migraine frequency correlates with poor sleep quality and a higher prevalence of poor sleepers. These associations occur in migraine with aura and without aura.

[Retroperitoneal lymph node metastasis in epithelial cancer of the ovary: a report of 58 cases].

OBJECTIVE: To analyze the retroperitoneal lymph node metastasis in epithelial cancer of the ovary and offer scientific indications for lymph node radical dissection. METHODS: Fifty-eight patients with ovarian cancer treated from January 1990 to December 2000 were retrospectively reviewed. Single-factor and multifactor analysis with Logistic regression model were performed by SPSS 10.0 statistic software. RESULTS: The metastasis rates of overall lymph nodes, pelvic nodes and para-aortic nodes were 48.3%, 37.9% and 25.9% respectively, among which no significant difference was noted (P > 0.05). Single-factor analysis showed that tumor location, ascitic condition, clinical stage and the size of residual tumor were associated with retroperitoneal lymph node metastasis. Multifactor analysis revealed that clinical stage and size of residual tumor were independent risk factors for metastasis of retroperitoneal lymph nodes. CONCLUSION: For early ovarian cancer patients, it is extremely important to perform radical dissection of the retroperitoneal lymph nodes. For advanced or residual lesions, radical dissection of pelvic nodes and para-aortic nodes could be considered in the second exploration.

Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples.

Human papillomavirus (HPV) DNA tests tend to show high sensitivity, but poor specificity in detecting high-grade cervical lesions. This study aimed to explore the clinical performance of QuantiVirus(®) HPV E6/E7 mRNA in identifying ≥Grade 2 cervical intraepithelial neoplasia. Thin-prep(®) liquid based cytology test (LBC) samples were collected from October 2009 to October 2011 from women who underwent outpatient hospital-based gynecological screening. LBC samples were processed for E6/E7 mRNA detection and HPV DNA detection. Of 335 patients, 135 (40.3%) were HPV E6/E7 mRNA positive for high-risk HPV subtypes. The positivity rate of HPV E6/E7 mRNA increased with the severity of cytological and histological evaluation. An optimal cut-off value of ≥567copies/ml was determined using receiver operating characteristic (ROC) curve, and positive predictive value and negative predictive value of cut-off value (≥567copies/ml) were higher than those of E6/E7 mRNA positivity only, but not significant. QuantiVirus(®) HPV E6/E7 mRNA testing may be a valuable tool in triage for identifying ≥Grade 2 cervical intraepithelial neoplasia. A high specificity and a low positivity rate of E6/E7mRNA testing as a triage test in HPV DNA-positive women can be translated into a low referral for colposcopy. Studies composed of large population-based samples of women and with rigorous disease ascertainment, are needed to establish the optimal cut-off point based on ROC curve analysis.

Epidemiology of hospitalized traumatic pelvic fractures and their combined injuries in Taiwan: 2000-2011 National Health Insurance data surveillance.

BACKGROUND: From the viewpoint of prehospital emergency medicine, a greater proportion of pelvic fractures not of a life-threatening status but combined with other injuries need more comprehensive recognition. METHODS: A 12-year nationwide health database of inpatients was reviewed. All cases diagnosed as pelvic fractures were enrolled. The associated injuries classified into 20 categories were further analyzed. RESULTS: During 2000-2011, the hospitalized incidence of pelvic fractures in Taiwan ranged from 17.17 to 19.42 per 100,000, and an increasing trend with age was observed. The mean case-fatality rate was 1.6% for females and 2.1% for males; male patients with pelvic fractures had a significantly higher risk of death than female patients after adjusting for other covariates. 74.2% of these cases were combined with other injuries. The most common associated injuries in an identified body region were other orthopedic fractures of the lower limbs (21.50%), spine/trunk (20.97%), or upper limbs (18.18%), followed by significant head injuries (17.59%), intra-abdominal injuries (11.00%), and thoracic injuries (7.20%). CONCLUSION: The incidence of hospitalized pelvic fractures in Taiwan was low and the case-fatality rate was lower than those of other countries. Concurrently, coexistence of major combined injuries with pelvic fractures was easily treated at medical centers.

[Biodegradation mechanism of DDT and chlorpyrifos using molecular simulation].

In order to explore the microscopic degradation mechanism of organic pesticides degrading enzymes, we used molecular docking method to investigate the binding modes of DDT to laccase and chlorpyrifos to organophosphorus hydrolase, and obtained the corresponding complex structures. According to the principle of minimum scoring, the results showed that the MolDock scores were -103.134 and -111.626, re-rank scores were -72.858 and -80.261, respectively. And we used LPC/CSU server search the interactions between organic pesticides and their degrading enzymes. Our results showed that hydrophobic interaction was the strongest contacts in DDT-laccase complex, and both hydrogen bonds and hydrophobic interactions were the strongest contacts when chlorpyrifos-organophosphorus hydrolase complex. The amino acid residues Tyr224 in laccase and Arg254 in organophosphorus hydrolase were detected to play significant roles in catalytic processes.

Compound microsatellites in complete Escherichia coli genomes.

Compound microsatellites consisting of two or more repeats in close proximity have been found in eukaryotic genomes. So far such compound microsatellites have not been investigated in any prokaryotic genomes. We have therefore examined compound microsatellites in 22 complete genomes of Escherichia coli, which is one of the ideal model organisms to analyze the nature and evolution of prokaryotic compound microsatellites. Our results indicated that about 1.75-2.85% of all microsatellites could be accounted as compound microsatellites with very low complexity, and most compound microsatellites were composed of very different motifs. Compound microsatellites were significantly overrepresented in all surveyed genomes. These results were dramatically different from those in eukaryotes. We discussed the possible reasons for the observed divergence.

Morphology of the tibial organs of acrididae: Comparison of subgenual and distal organs in fore-, mid-, and hindlegs of Schistocerca gregaria (Acrididae, Catantopinae) and Locusta migratoria (Acrididae, Oedipodinae).

The structure of the complex tibial organs in the fore-, mid-, and hindlegs of two grasshopper species, Schistocerca gregaria (Acrididae, Catantopinae) and Locusta migratoria (Acrididae, Oedipodinae), is described. In each leg the tibial organs consist of two scolopale organs: the subgenual organ and the distal organ. Both organs are located in the hemolymph channel. The subgenual organ has a sail-like structure, and its scolopidia are oriented perpendicular to the long axis of the leg. The number of scolopidia in the subgenual organs is lower in Locusta migratoria than in Schistocerca gregaria. The scolopidia of the distal organ are clearly spearated from those of the subgenual organ and lie parallel with the long axis of the legs. They insert distally on an attachment plate that lies in the hemolymph channel. The subgenual organs and the distal organs are smaller in the hindlegs than in the fore- and midlegs, and this difference is especially pronounced in Locusta migratoria. The complex tibial organ of Locusta and Schistocerca is very similar in structure and cellular composition with that of Periplaneta (Blattidae). In tettigoniids and gryllids the distal organ is differentiated into an intermediate organ and the crista acoustica. © 1995 Wiley-Liss, Inc. © 1995 Wiley-Liss, Inc.

Complex tibial organs in fore-, mid-, and hindlegs of the bushcricket Gampsocleis gratiosa (Tettigoniidae): Comparison of morphology of the organs.

The structure of the complex tibial organs in the fore-, mid-, and hindlegs of the East Asian bushcricket Gampsocleis gratiosa (Tettigoniidae, Decticinae) is described comparatively. In each leg the tibial organs consist of three scolopale organs: the subgenual organ, the intermediate organ, and the crista acoustica. Only in the forelegs are the tibial organs differentiated as tympanal organs, and sound transmitting structures (acoustic trachea, tympana, and tympanal covers) are present. The morphology of the tracheae in the mid- and hindlegs is significantly different from that found in the forelegs. The number of scolopidia in the subgenual organ is highest in the midleg and lowest in the foreleg; in the intermediate organ the number is also highest in the midleg, and the fore- and hindleg contain 40% fewer scolopidia. In the crista acoustica, the number of scolopidia decreases from, the fore- to the mid- and hindlegs. The morphology and the dimensions of the scolopidia and the attachment structures within the crista acoustica of the mid- and hindlegs differ strongly from those in the foreleg. The results indicate that, in addition to the presence of a sound transmitting system, the specific differentiations within the crista acoustica are important for the high auditory sensitivity of the tibial organs in the forelegs. © 1994 Wiley-Liss, Inc.