Search

Background: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. Objective: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. Methods: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. Results: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. Conclusion: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro. [ABSTRACT FROM AUTHOR]

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target. [ABSTRACT FROM AUTHOR]

HMOs (Human milk oligosaccharide) has an impact on maternal and infant health. Colostrum samples of 70 breastfeeding women in China were collected and recorded clinical characteristics. The major oligosaccharides and microbiota were quantitated in colostrum. The concentration of fucosylated HMOs in primipara was higher than that of multipara (p = 0.030). The concentration of N-acetylated HMOs in vaginal delivery milk was less than that of cesarean (p = 0.038). Non-fucosylated HMOs of breastfeeding women were less than that of breast pump (p = 0.038). Meanwhile, the concentration of LNT was positively correlated with Lactobacillus (r = 0.250, p = 0.037). DS-LNT was negatively correlated with Staphylococcus (r = – 0.240, p = 0.045). There was a positive correlation of Streptococcus with LNFP II (r = 0.314, p = 0.011) and 3-SL (r = 0.322, p = 0.009). In addition, there was a negative correlation between 2'-FL and 3-FL (r = – 0.465, p = 0.001). There was a positive correlation between LNT and LNnT (r = 0.778, p = 0.001). Therefore, the concentration of HMOs is related to number of deliveries, delivery mode, lactation mode and perinatal antibiotic. The concentration of HMOs is related to Lactobacillus, Streptococcus and Streptococcus in colostrum. In addition, there are connections between different oligosaccharides in content. The study protocol was also registered in the ClinicalTrails.gov (ChiCTR2200064454) (Oct. 2022). [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL), which can be influenced by various aspects, especially socioeconomic status and lifestyle, has been identified as an important predictor of the prognosis of older adults. Dietary habit, a major part of lifestyle, can affect the nutritional status, which is closely correlated with the development of geriatric syndromes in the elderly. Aims: The aim of the study was to examine the association of HRQoL, socioeconomic status, and lifestyle with the risk and severity of sarcopenia, a geriatric syndrome characterized by progressive loss of skeletal muscle mass, strength and function. Methods: A cross-sectional retrospective study with 2877 participants aged ≥65 years was performed. HRQoL was assessed using EuroQoL Five Dimensions questionnaire. Socioeconomic status was assessed by the educational attainment, occupation, and household income. Lifestyle was assessed using 12 items closely related to Chinese living habits. The information of daily dietary habits including tea, alcohol, type of diet, and volume of drinking water were collected. The associations of HRQoL, socioeconomic status, and lifestyle with the risk of sarcopenia were examined by multivariate regression logistical analysis. The potential causal role of age, body mass index, and waist circumference in the effect of HRQoL on sarcopenia risk was analyzed by causal mediation analysis. Results: High HRQoL [adjusted odds ratio (OR) =0.85, 95% confidence interval (CI) =0.69–0.95, P=0.034] and household income levels (adjusted OR =0.74, 95% CI =0.57–0.95, P=0.019) were inversely associated with the risk of sarcopenia. Meanwhile, more consumption of spicy food (adjusted OR =1.34, 95% CI =1.09–1.81, P =0.037) and occasionally drinking (adjusted OR =1.46, 95% CI =1.07–2.00, P =0.016, as compared to those never drinking) were associated with higher risk of sarcopenia, while skipping breakfast occasionally (adjusted OR =0.37, 95% CI =0.21–0.64, P <0.001, as compared to those eating breakfast every day) and less consumption of salt (adjusted OR =0.71, 95% CI =0.52–0.96, P =0.026, as compared to those consuming high amount of salt) were associated with lower risk of sarcopenia. Further causal mediation analysis aimed to explore how much age, body mass index, and waist circumference might explain the effect of HRQoL on the risk of sarcopenia showed that the estimated proportion that mediated the effect of HRQoL on the risk of sarcopenia by age was 28.0%. Conclusions: In summary, our findings demonstrate that low levels of HRQoL and household income, more intake of salt and spicy food, and occasional intake of alcohol are correlated with higher risk of sarcopenia, while skipping breakfast occasionally is associated with lower risk of sarcopenia in a Chinese population of older adults. [ABSTRACT FROM AUTHOR]

In this study, the nonlinear second harmonic generation(SHG) and third harmonic generation(THG) in a GaAlAs/GaAs Rosen–Morse quantum well(QW) are studied theoretically. The analytical expressions of the SHG and THG of the Rosen–Morse QW are given systematically by using the density matrix theory and the iterative method. Also, the energy levels and the wave function of the Rosen–Morse QW system are gained with finite difference method. The effects of the structure parameter and applied electric field on energy levels and nonlinear optical properties are discussed in detail. It is found that the nonlinear SHG and THG are closely related to the structure parameter and applied electric field. The result show that the red- and blue-shift of the resonance peaks of the nonlinear SHG and THG of the system can be achieved by adjusting the system parameters, and the optimal system parameter for obtaining the maximum peak intensity are given. [ABSTRACT FROM AUTHOR]

Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation. SARM1 is a key player in axon degeneration. Here, the authors generate a nanobody, which specifically recognizes the NMN-bound state of SARM1 and helps resolve the SARM1 structure in an intermediate state of activation. [ABSTRACT FROM AUTHOR]

Objective: Endogenous adenosine 5′-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. Methods: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. Results: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = − 0.348) and asthma quality of life questionnaire scores (r = − 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. Conclusion: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma. [ABSTRACT FROM AUTHOR]

Topography effect is involved in the liquefiable canyon ground, which will cause variations of canyon slope displacement and liquefaction zone. To capture these salient response characteristics, a series of two-dimensional plane strain finite element models are created with various canyon sizes. Single soil stratum and constant water level are considered in these models, and detailed modeling techniques are presented. Computed static and dynamic results are illustrated and discussed. Effect of canyon size on initial horizontal stress disturbance region is explored. Specific attention should be paid to the remarkable changes in liquefaction location due to variation of canyon size, which can be used to estimate liquefaction zone. Modeling techniques and insights from this study are of significance to foundation design and liquefaction resistance. [ABSTRACT FROM AUTHOR]

African cultivated rice (Oryza glaberrima Steud) contains many favorable genes for tolerance to biotic and abiotic stresses and F1 hybrids between Asian cultivated rice (Oryza sativa L.) show strong heterosis. However, the hybrids of two species often exhibit hybrid sterility. Here, we identified a male sterility locus qHMS4 on chromosome 4 (Chr.4), which induces pollen semi-sterility in F1 hybrids of japonica rice variety Dianjingyou1 (DJY1) and a near-isogenic line (NIL) carrying a Chr.4 segment from Oryza glaberrima accession IRGC101854. Cytological observations indicated that non-functional pollen grains produced by the hybrids and lacking starch accumulation abort at the late bicellular stage. Molecular genetic analysis revealed distorted segregation in male gametogenesis carrying qHMS4 allele from DJY1. Fine-mapping of qHMS4 using an F2 population of 22,500 plants delimited qHMS4 to a region of 110-kb on the short arm of Chr.4. Sequence analysis showed that the corresponding sequence region in DJY1 and Oryza glaberrima were 114-kb and 323-kb, respectively, and that the sequence homology was very poor. Gene prediction analysis identified 16 and 46 open reading frames (ORFs) based on the sequences of DJY1 and O. glaberrima, respectively, among which 3 ORFs were shared by both. Future map-based cloning of qHMS4 will help to understand the underlying molecular mechanism of hybrid sterility between the two cultivated rice species. [ABSTRACT FROM AUTHOR]

Evidence indicates that age-related macular degeneration (AMD) is associated with the prior presence of allergic diseases; however, large-scale studies in the literature are limited. A case–control study was conducted to describe the relationship between premorbid allergic diseases and AMD using Taiwan's National Health Insurance database. Eligibility criteria for inclusion of new adult AMD cases from 2000 to 2013 were set up. We defined the year of diagnosis as the index year. Age-, gender-, index year- matched controls who were drawn from the same database. The case control ratio was 1:4. For all participants, all premorbid conditions staring 1996 to index year were documented. Binary logistic regression was used to describe factors related to AMD occurrence. The AMD group consisted of 10,911 patients, and the comparison group consisted of 43,644 individuals. Patients with AMD showed significant associations with premorbid allergic diseases (aOR 1.54, 95% CI 1.47–1.61), specifically with allergic conjunctivitis (aOR 2.07, 95% CI 1.94–2.20), allergic rhinitis (aOR 1.32, 95% CI 1.25–1.39), asthma (aOR 0.99, 95% CI 0.93–1.06), and atopic dermatitis (aOR 1.04, 95% CI 0.94–1.17). Further analyses indicated that patients with more concurrent allergic diseases have higher associations with AMD than those with fewer concurrent diseases. Patients with more annual medical visits for their allergic diseases also showed higher associations with AMD than those with fewer visits. AMD is significantly associated with premorbid allergic diseases. The underlying mechanisms must be further investigated. [ABSTRACT FROM AUTHOR]

Due to the features of light weight, high flexibility, and slight damping, large-scale spatial structures are very sensitive to wind load. Thus, special attention must be paid to wind effect on large-scale spatial structures. A wind pressure field measurement was carried out to characterize the actual wind pressure of a large-span spatial structure. Meanwhile, it is also intended to provide reliable full-scale measurements for verification of wind tunnel test results widely used in the design and construction of structure. In this study, both wind tunnel test and field measurement are utilized to investigate the properties of the wind pressure acting on a typical large-scale spatial structure. Specifically, wind pressure coefficients, spatial distribution, probability density distribution (PDF), non-Gaussian characteristics, and power spectral density (PSD) are fully compared and discussed based on the results of the wind tunnel test and long-term field measurement. The comparison results show that generally the results of the wind tunnel test have good agreement with those of the field measurement. In the meanwhile, the discrepancies between them are also observed. This study aims to fully investigate the wind effects on large-scale spatial structure and enhance the understanding of wind loads. [ABSTRACT FROM AUTHOR]

Species diversity exhibit a close relationship with ecosystem services, and making clear the relationship can help us understand the service value and functional mechanism of ecosystems and take measures to promote human well-being. Here, we used species survey data and multi-source habitat factors to simulate the spatial distribution of species richness and four types of ecosystem services (water production, net primary productivity, carbon storage, and habitat quality) in Sanjiangyuan National Park located in Qinghai Province, China. We also analyzed the spatial distribution pattern and explored the spatial relationship between species richness and ecosystem services through GeoDetector analyses. We found that high species richness in Sanjiangyuan National Park was shown to be mainly distributed in areas with high vegetation growth on both sides of rivers. The effect of climate on the spatial distribution of species richness in the park is the highest among all the selected environmental variables. For the relationship between species diversity and ecosystem services, the relative correlation strength of single ecosystem service varied among the three main ecosystems (grassland, meadow, and wetland) and all relations are positive. [ABSTRACT FROM AUTHOR]

Proper deformation process is essential for forming the shape of cable net structures during construction. This highlights the importance of identifying uneven and excessive deformation when building large-scale cable net structures. As such, the deformation of large-scale cable net structures should be accurately monitored in a real-time manner during the construction process. This study is to develop a laser-based displacement monitoring system for tracing the real-time deformation of large-scale spatial structures. The developed displacement monitoring system combines wireless sensor networks (WSN) and laser ranging technology. The laser-based displacement monitoring system is implemented on the National Speed Skating Oval (NSSO), which is a large-scale cable net structure, to obtain the relative displacement change between the cable net structure and the supporting system. On the other hand, the finite element (FE) model of the NSSO is established to simulate the deformation process. Then, the measured displacement results are compared with the FE model-derived counterparts. It is shown that the simulated and measured results have a good agreement, which indicates the effectiveness of the laser-based displacement monitoring system. [ABSTRACT FROM AUTHOR]

Wind speed and wind direction are two important factors to describe the wind properties. The statistical probability model of wind speed and wind direction is widely used to characterize the uncertainty of wind field around the structures. Considering the correlation between the wind speed and wind direction, they should be modeled simultaneously, which highlights the importance of using joint probability density function (JPDF) to describe the wind properties. An angular–linear (AL) model is employed to construct the JPDF of wind speed and wind direction based on long-term monitoring data. The finite mixture (FM) Gumbel distribution, which models the wind speed, and the FM von Mises distribution, which models the wind direction, are proposed to formulate the AL model. Expectation–maximization (EM) and genetic algorithm (GA) are adopted to estimate the AL model parameters. For the EM method, the analytical expressions for calculating the AL model parameters are derived. For the GA method, the analytical fitness functions are derived. These derived analytical expressions facilitate the implementation of the EM and GA methods. One-year wind monitoring data collected by structural health monitoring (SHM) system installed on Jiubao Bridge is employed to demonstrate the feasibility of the AL model-based method in evaluating the wind properties. The results show that the AL model formulated by the FM Gumbel distribution and FM Von Mises distribution is effective for establishing JPDF for joint modeling of the wind speed and wind direction. In the AL model, the EM method is more effective for estimating the parameters of the FM von Mises distribution, whereas the GA methods is more powerful for estimating the parameters of the FM Gumbel distribution. [ABSTRACT FROM AUTHOR]

EP300-ZNF384 fusion is a rare recurrent cytogenetic abnormality associated with B cell acute lymphoblastic leukemia (B-ALL), which was rarely studied in Chinese patient cohort. Here, we used a customized RNA fusion gene panel to investigate gene fusions in 56 selected acute leukemia patients without conventional genetic abnormalities. Two EP300-ZNF384 fusion forms were detected in ten cases, which were in-frame fusions of EP300 exon 6 fused with exon 3 or 2 of ZNF384. The fusions led to the lack of most functional domains of EP300. We firstly reported EP300-ZNF384 fusion in a mixed-phenotype acute leukemia (MPAL) patient whose CD33 and CD13 were negative. The rest nine B-ALL patients with EP300-ZNF384 fusion expressed CD33 and/or CD13. Fifty-six percent of B-ALL patients (5/9) with EP300-ZNF384 fusion were positive with CD10. After the diagnosis of EP300-ZNF384 fusion, 70% of the patients achieved remission after chemotherapy. Our observations indicated that EP300-ZNF384 fusion consists of a distinct subgroup of B-ALL with a characteristic immunophenotype. These patients are sensitive to current chemotherapy regimen and have an excellent outcome. [ABSTRACT FROM AUTHOR]

The accurate and reliable fruit detection in orchards is one of the most crucial tasks for supporting higher level agriculture tasks such as yield mapping and robotic harvesting. However, detecting and counting small fruit is a very challenging task under variable lighting conditions, low-resolutions and heavy occlusion by neighboring fruits or foliage. To robustly detect small fruits, an improved method is proposed based on multiple scale faster region-based convolutional neural networks (MS-FRCNN) approach using the color and depth images acquired with an RGB-D camera. The architecture of MS-FRCNN is improved to detect lower-level features by incorporating feature maps from shallower convolution feature maps for regions of interest (ROI) pooling. The detection framework consists of three phases. Firstly, multiple scale feature extractors are used to extract low and high features from RGB and depth images respectively. Then, RGB-detector and depth-detector are trained separately using MS-FRCNN. Finally, late fusion methods are explored for combining the RGB and depth detector. The detection framework was demonstrated and evaluated on two datasets that include passion fruit images under variable illumination conditions and occlusion. Compared with the faster R-CNN detector of RGB-D images, the recall, the precision and F1-score of MS-FRCNN method increased from 0.922 to 0.962, 0.850 to 0.931 and 0.885 to 0.946, respectively. Furthermore, the MS-FRCNN method effectively improves small passion fruit detection by achieving 0.909 of the F1 score. It is concluded that the detector based on MS-FRCNN can be applied practically in the actual orchard environment. [ABSTRACT FROM AUTHOR]

Voxel-based morphometry (VBM) is a popular non-invasive magnetic resonance imaging technique to investigate brain gray matter (GM) differences between groups. Recently, two VBM studies in migraine have been published in The Journal of Headache and Pain. Reviewing the two and those previous published VBM studies, we found considerable variations of the results. Spatially diverse brain regions with decreased and increased GM alterations and null findings have been reported. It is interesting to know whether there is a reliable brain morphological signature for migraine. Coordinate-based meta-analysis (CBMA) is increasingly used to quantitatively pool individual neuroimaging studies to identify consistent and reliable findings. Several CBMA have been conducted, however, their results were inconsistent. The algorithms for CBMA have evolved and more eligible VBM studies in migraine have been published. We therefore conducted an updated CBMA using the latest algorithms for CBMA, seed-based d mapping with permutation of subject images (SDM-PSI). The present CBMA of 32 VBM studies (41 datasets comprising 1252 patients and 1025 healthy controls) found no evidence of consistent GM alterations in migraine. Sensitivity analysis, subgroup meta-analyses, and meta-regression analyses revealed that the result was robust. This negative result indicates that there is no reliable brain morphological signature for migraine. VBM investigations in migraine remain a heterogeneous field. Many potential confounding factors, such as underpowered sample sizes, variations in demographic and clinical characteristics, and differences in MRI scanners, head coils, scanning parameters, preprocessing procedures, and statistical strategies may cause the inconsistences of the results. Future VBM studies are warranted to enroll well-characterized and homogeneous subtype samples with appropriate sample sizes, comprehensively assess comorbidities and medication status, and use well-validated and standardized imaging protocols and processing and analysis pipelines to produce robust and replicable results in migraine. [ABSTRACT FROM AUTHOR]

A deep learning-based single image deraining algorithm is proposed in this work. Instead of modeling a rain layer as a linear function between the rain image and its clear version as previous works do, we directly formulate the clear image as the result of a non-linear mapping of thrain image. We construct a coarse deraining convolutional network and a refinement convolutional network to learn this non-linear mapping function. The coarse deraining network is trained to detect the rain streaks with different directions, and restore a raw derained result. The refinement network aims at refining the result according to the raw derained image and the original rain image. By combining the two networks, we are able to well-restore the rain-free image. Experimental results demonstrate that the proposed deraining method can produce high-quality clear images from both synthetic and real-world rain images, outperforming the state-of-the-art methods qualitatively and quantitatively. [ABSTRACT FROM AUTHOR]

Background: The current study followed-up site-specific cancer risks in an unique cohort with 30 years' follow-up after long-term low-dose-rate radiation exposure in Taiwan.Methods: Six thousand two hundred and forty two Taiwanese people received extra exposure in residential and school buildings constructed with Co-60-contaminated steel from 1982 until informed and relocated in early 1990s. The additional doses received have been estimated. During 1983-2012, 300 cancer cases were identified through the national cancer registry in Taiwan, 247 cases with minimum latent periods from initial exposure. The hazard ratios (HR) of site-specific cancers were estimated with additional cumulative exposure estimated individually.Results: Dose-dependent risks were statistically significantly increased for leukaemia excluding chronic lymphocytic leukaemia (HR100mSv 1.18; 90% CI 1.04-1.28), breast cancers (HR100mSv 1.11; 90% CI 1.05-1.20), and all cancers (HR100mSv 1.05; 90% CI 1.0-1.08, P=0.04). Women with an initial age of exposure lower than 20 were shown with dose response increase in breast cancers risks (HR100mSv 1.38; 90% CI 1.14-1.60; P=0.0008).Conclusions: Radiation exposure before age 20 was associated with a significantly increased risk of breast cancer at much lower radiation exposure than observed previously. [ABSTRACT FROM AUTHOR]

Background Optimization of the area under the concentration-time curve (AUC) of busulfan, an essential component of conditioning regimens, improves the outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT). Traditional sampling methods for calculating AUC require multiple sampling. Objective To establish a limited sampling strategy for predicting the AUC0-12 of intravenous busulfan for Chinese adult patients prior to HSCT. Methods The pharmacokinetics of twice-daily intravenous busulfan was studied in forty-five Chinese adult patients. Limited sampling models were established by the multiple linear regression analysis. The prediction error (PE) and the absolute prediction error (APE) were calculated to evaluate predictive accuracy. The agreement between the predicted and actual AUC0-12 was investigated by the Bland-Altman analysis. The accuracy and robustness of the models was validated by the bootstrap analysis. Results The AUC0-12 values of the 1st and 7th doses of busulfan were 1491 ± 403.7 and 1908 ± 518.5 μmol L-1 min, respectively. The 2-sample model suggested that the predicted AUC0-12 of twice-daily intravenous busulfan could be calculated using the following equation: AUC0-12 = 40.017 + 0.955 × C3 + 1.088 × C6 with r2 = 0.919. The mean PE and APE of the model were 0.52 ± 7.67 and 6.32 ± 4.27%, respectively. Conclusion The 2-sample model is an effective and reliable approach to predict the AUC0-12 of twice-daily intravenous busulfan in Chinese adult patients. [ABSTRACT FROM AUTHOR]

Blood pressure variability has a great effect on the progression of arterial stiffness, which has increasingly become a hot research topic recently. In this study, beat-to-beat recordings of blood pressure (BP), heart rate, cardiac output, total peripheral resistance, and left ventricular ejection time during the cold pressor test (CPT) were analyzed together. We recruited 101 young Chinese subjects (aged 21-33) with no known history of high BP into the study. We found that the mean level of beat-to-beat BP and the average real variability and successive variation of beat-to-beat diastolic BP variability in the CPT showed significant correlations with pulse wave velocity (PWV) ( r = 0.22-0.34, P < 0.05). In addition, we also found correlations between beat-to-beat heart rate and heart rate variability indices and PWV in each phase of the CPT. At the same time, the standard deviation of the R-R intervals and square root of the mean squared difference of successive R-R intervals in the cold stimulus phase also showed significant correlations with PWV ( r = 0.23-0.24, P < 0.05). In conclusion, the level and variability of beat-to-beat BP have a strong influence on arterial stiffness. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). Methods: Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using the Bayesian estimator. Comparisons of mean values were analyzed using SPSS 11.0. Results: The average daily dose of vancomycin was 15.0 ± 3.7 mg/kg (q 12 h). Sixty-seven trough concentrations were collected. Compared with the recommended standard vancomycin trough concentration (15 mg/L), SAP patients had significantly lower vancomycin trough concentrations (6.1 ± 3.0 mg/L; p < 0.0001) while the volume of distribution (Vd) and clearance (CL) of vancomycin were significantly increased. Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age and albumin but also with the duration from SAP onset to vancomycin therapy ( p < 0.0001). Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration ( r = 0.456). The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin therapeutic drug monitoring (TDM) within or over 4 weeks. Early group had much lower trough concentrations compared to late group, and the CL was also significantly increased in the early group. Of these 67 patients, 24 patients made vancomycin dosage adjustment (increased to 18.5 ± 3.9 mg/kg, q 12 h) and the average trough concentrations increased to 12.6 ± 3.8 mg/L. Conclusions: The serum trough concentration of vancomycin was significantly reduced in SAP patients. Higher dosage regimens are needed to ensure the clinical effect. [ABSTRACT FROM AUTHOR]

Phenylpropanoids are widely used in food supplements, pharmaceuticals, and cosmetics with diverse benefits to human health. Trans-cinnamic acid or p-coumaric acid is usually used as the starting precursor to produce phenylpropanoids. Synthetic bioengineering of microbial cell factories offers a sustainable and flexible alternative method for obtaining these compounds. In this study, a constitutive expression system consisting of Rhodotorula glutinis phenylalanine/tyrosine ammonia lyase was developed to produce a phenylpropanoic acid precursor in Escherichia coli. To improve trans-cinnamic acid and p-coumaric acid production, BioBrick optimization was investigated, causing a 7.2- and 14.2-fold increase in the yield of these compounds, respectively. The optimum strain was capable of de novo producing 78.81 mg/L of trans-cinnamic acid and 34.67 mg/L of p-coumaric acid in a shake flask culture. The work presented here paves the way for the development of a sustainable and economical process for microbial production of a phenylpropanoic acid precursor. [ABSTRACT FROM AUTHOR]

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM ( n = 247), MTX and SSZ ( n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, ( P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, ( P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, ( P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects. [ABSTRACT FROM AUTHOR]

This paper proposes a game theoretic approach for concurrent tolerance design considering the practical manufacturing process and assembly process, to achieve lower manufacturing cost and good product assemblability. The optimization objectives and constraints for concurrent tolerance design for manufacture and assembly are discussed, and the key technologies for concurrent tolerance design with game theory are investigated, including the strategy set division, payoff calculation, and Nash equilibrium evolution. An optimization algorithm is proposed to achieve concurrent tolerance design with a game theoretic approach, and the genetic algorithm is used to conclude the Nash equilibrium of the game for manufacture and assembly. Finally, a case study is given to verify the proposed approach. [ABSTRACT FROM AUTHOR]

Two 5,10,15,20-tetraphenylporphyrins with one phenyl group anchored to a rhodanine-terminated side chain, RhD–TPP and RhDCOOH–TPP, were designed and synthesized, and their protein photocleavage activities were investigated using bovine serum albumin (BSA) as a model protein. Both porphyrins exhibit similar absorption spectra, fluorescence spectra, fluorescence quantum yields, and singlet oxygen (1O2) quantum yields in organic solvents due to their structure similarity. They also show similar binding affinities and binding sites toward BSA. However, RhD–TPP is nearly inactive in protein photocleavage while RhDCOOH–TPP can lead to distinct photocleavage of BSA under the same experimental conditions. Such a difference may be attributed to the different binding modes of the two porphyrin derivatives toward BSA, though the apparent binding affinities and the binding sites are similar, and consequently a great difference in the 1O2 quantum yields of the two porphyrins bound on BSA. The presence of the COOH group in RhDCOOH is proposed to play an important role, leading to less hydrophobic character and additional interactions towards BSA. [ABSTRACT FROM AUTHOR]

The −159C/T polymorphism in the CD14 gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study is to investigate the association between the −159C/T polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on April 20, 2010). Statistical analysis was performed by using the softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17 articles (4,246 cases and 3,631 controls) were included in this meta-analysis. There was no association between this polymorphism and asthma risk in combined analyses (odds ratio (OR) = 0.86 and 95% confidence interval (95% CI) = 0.72-1.02, P = 0.09 for TC + TT vs. CC). In the subgroup analysis by age, ethnicity, and atopic status, no significant associations of asthma risks were obtained from age groups, ethnic groups, and atopic groups for TC + TT vs. CC comparison. For atopic population, significant decreased atopic asthma risks were found among Asian population (OR = 0.69, 95% CI 0.52-0.92, P = 0.01) and children population (OR = 0.69, 95% CI 0.54-0.89, P = 0.0004) for TC + TT vs. CC comparison. This meta-analysis suggests that CD14 is a candidate gene for atopic asthma susceptibility. The −159C/T polymorphism may be a protective factor for atopic asthma in Asian and children. More studies are needed to validate these associations. [ABSTRACT FROM AUTHOR]

Based on experimental results, the transformation kinetics and cooling characteristics of low-carbon steel were analyzed and modeled to quantitatively link the operational parameters of a process with the properties. From the continuous cooling transformation results, comparisons of the start temperature of austenite-ferrite transformation among three models were analyzed, and the optimal ln k and n, which are the parameters in the Avrami equation, were determined by applying two regression models at different cooling rates. The transformation kinetics during continuous cooling was determined. Furthermore, reasonable agreements between experimental results and predictions were obtained, which can demonstrate the rationality of the established models. [ABSTRACT FROM AUTHOR]

Through fine tuning of synthesis conditions, we successfully synthesized three types of carbon nanofiber (CNF) (herring-bone carbon nanofiber, platelet carbon nanofiber, and cup-stacked carbon nanofiber) by the thermal decomposition of a mixture of poly(ethylene glycol) (PEG) and nickel chloride (NiCl2). A series of experimental results demonstrated that the key factors for the selective synthesis of these CNFs were the (1) NiCl2/PEG ratio, (2) drying time of the polymeric mixture, (3) state of PEG (liquid or solid) before temperature rising, and (4) temperature profile during the thermal decomposition. Changes in these conditions contributed to the formation of Ni catalyst particles from the catalyst NiCl2 with different morphology, thereby resulting in the growth of different types of CNF or amorphous carbon products according to the catalyst particle’s shape. Also, we found that the mechanism of CNF growth in this synthesis method was fundamentally the same as that in chemical vapor deposition (CVD). [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of biophysical parameters retrieved from remotely sensing data, a new algorithm was presented by using spatial contextual to estimate canopy variables from high-resolution remote sensing images. The developed algorithm was used for inversion of leaf area index (LAI) from Enhanced Thematic Mapper Plus (ETM+) data by combining with optimization method to minimize cost functions. The results show that the distribution of LAI is spatially consistent with the false composition imagery from ETM+ and the accuracy of LAI is significantly improved over the results retrieved by the conventional pixelwise retrieval methods, demonstrating that this method can be reliably used to integrate spatial contextual information for inverting LAI from high-resolution remote sensing images. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Rates of protein synthesis (lCPS) along the entire rostral to caudal extent of the hypoglossal nucleus were determined in adult, female rats with the quantitative autoradiographic l-[1-C]leucine method two and five weeks after unilateral hypoglossal axotomy with and without chronic treatment with testosterone. Rates of protein synthesis were increased on the axotomized side, and the increases were greater in the rostral portion of the nucleus at both time points examined. The effects of axotomy on lCPS were less at five weeks post-axotomy than at two weeks. In spite of the fact that testosterone has been shown to accelerate both the rate of outgrowth of regenerating cranial motor nerves (Kujawa et al., J. Neurosci. 11∶3898-3906, 1991) and the recovery of function (Kujawa et al., Exp. Neurol. 105∶80-85, 1989) and to attenuate the loss of neurons (Yu et al., Exp. Neurol. 80∶349-360, 1983) there were no effects of testosterone on 1CPS in the hypoglossal nucleus in either sham-operated or axotomized rats. [ABSTRACT FROM AUTHOR]

In Taiwan, the prevalence of myopia in children between 6 and 18 years old is over 80%, and high myopia accounts for over 20%, which turned out to be in the leading place worldwide. Orthokeratology and low-dose atropine are proven treatments to reduce myopia progression, though the potential corneal disturbances remain an issue in young populations. The alteration of the tear film is widely discussed but there is no consensus to date, so we aim to investigate the tear film spatial instability in children with myopia control using atropine or orthokeratology. Thirty-eight treatment-naïve participants and 126 myopic children under treatments were enrolled. The ocular surface homeostasis, spatial distribution of tear break-up, and high-order aberrations (HOAs) of the corneal surface were assessed. We found out that myopic children treated with either atropine or orthokeratology showed ocular surface homeostasis similar to that in treatment-naïve children. Nevertheless, children treated with orthokeratology presented higher HOAs (p < 0.00001) and a tendency of the first tear break-up zone at the inner half of the cornea (p = 0.04). This unique spatial instability of the tear film associated with myopia treatment might provide a more focused way of monitoring the pediatric tear film instability. [ABSTRACT FROM AUTHOR]

Fluid overload is a potential complication of hysteroscopic procedures with the possibility of dangerous electrolyte changes. This prospective randomized controlled trial aimed to compare perioperative outcomes and changes in electrolytes after hysteroscopic procedures between the manual infusion (MI) and the pump infusion (PI) methods for distending media infusion. One hundred consecutive women who had hysteroscopic procedures between December 2013 and February 2017 were recruited and randomly allocated to either the MI or PI group. The PI group was associated with an increased volume of infused fluid and collected fluid compared with the volumes of the MI group. Almost all serum electrolyte levels differed significantly between the baseline and postoperative values in both groups; however, no significant differences were noted between the groups. The change in potassium level was positively correlated with the volume of fluid deficit (Spearman's rho = 0.24, P = 0.03), whereas the change in calcium level was negatively correlated with the volume of fluid deficit (Spearman's rho = −0.26, P = 0.046). With no between-group differences in the changes in the other perioperative parameters and electrolytes, the MI method can be a good alternative for delivering distending media for hysteroscopic procedures. [ABSTRACT FROM AUTHOR]

Background: Although many epidemiological studies have presented road traffic injuries (RTIs) according to the victim’s mode of transport, very few have mentioned the mode of transport of the victim’s counterparts. We sought to use matrix frame to present the pattern of RTIs based on the International Classification of Diseases, Tenth Revision (ICD-10) codes.Methods: Patients admitted to Hualien Tzu Chi Hospital, Taiwan, for RTIs from January 1, 2013 to December 31, 2016 were included. The numbers and proportions of various crash types of RTIs were presented using a matrix frame. The row margin of the matrix is the second character of ICD-10 codes V00-V79 (victim’s mode of transport), and the column margin of the matrix is the third character of ICD-10 codes V00-V79 (mode of transport of victim’s counterpart), constituting a 80-cell grid.Results: In total, 2727 patients were included. The cell with the highest proportion in the matrix grid was ICD-10 code V23 “motorcycle rider injured in collision with car, pick-up truck or van” (27.0%, 737/2727), followed by that of V27 “motorcycle rider injured in collision with fixed or stationary object” (12.5%, 342/2727) and V28 “motorcycle rider injured in noncollision transport accident” (12.2%, 334/2727). The matrix pattern of RTIs differed with sex and age.Conclusions: By using the matrix frame, we can easily understand the RTI pattern for different demographic groups and identify the priority crash types. [ABSTRACT FROM AUTHOR]

Proper intracellular Ca[sup2+] signaling is essential for cell functions. However, the significance of intracellular calcium concentration ([Ca[sup2+]][subi]) regulated by Ca[sup2+] release from endoplasmic reticulum (ER) during early developmental stage of myocytes and neuronal cells have not yet been fully understood. It is believed that endoplasmic reticulum (ER)-function is rudimentary in the fetal heart and embryonic stem cell (ESC) derived cardiomyocytes (ESCMs). Also it remains unclear whether intracellular Ca[sup2+] mobilization from type 2 ryanodine receptor (RyR2) is required in the activity-dependent neurogenesis. Using murine ESCs as an in vitro model of cardiomyogenesis and neurogenesis, we demonstrate that functional RyR2 are essential to the rapid upstroke and frequency of Ca[sup2+] transients, which regulate contractions with the differentiation of ESCMs; and neurogenesis induced by activation of GABA[subA] receptors and L-type Ca[sup2+] channels depends critically on the functional RyR2. These results reveal that ESCMs have the potential to form a functional ER that is necessary for eventual therapeutic viability. An intimate cooperation of L-type Ca[sup2+] channels with RyR2 is crucial for the activity-dependent neurogenesis induced by paracrine and/or autocrine GABA signaling. [ABSTRACT FROM AUTHOR]