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The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD2 actions in guinea pig out-flow region and the distribution of DP1/ DP2 receptors. The effects of PGD2 on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP1/ DP2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP1/ DP2 receptors. PGD2 in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation ( EFS) and inhibited spontaneous contractions of the proximal urethra. PGD2 was equally (trigone) or slightly less potent (urethra) compared with PGE2. Expression of DP1 and DP2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP1 and DP2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD2 may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground Intrathecal morphine (ITM) has proven to be excellent in reducing postoperative pain. However, its use is associated with the occurrence of postoperative nausea and vomiting (PONV). In this study, we wish to compare the efficacy between the combination therapy of granisetron and dexamethasone versus granisetron alone on the occurrence of postoperative nausea and vomiting (PONV) in parturients undergoing elective Caesarean delivery.Method This is a prospective double-blinded, randomised controlled trial (RCT) involving 126 parturients of American Society of Anesthesiologist (ASA) physical status I and II undergoing elective Caesarean deliveries. Subjects were randomly allocated into 2 groups (n = 63), to either receive a combination of 1 mg intravenous (IV) granisetron plus 4 mg IV dexamethasone (Group A) or to receive 1 mg IV granisetron (Group B). They were assessed at 1, 4, 8, 12 and 24-hour postoperatively. Episodes of nausea, retching, vomiting and the requirement of rescue antiemetics at these time intervals were recorded.Results There are no statistically significant differences in the occurrence of nausea, retching and vomiting between both groups at 1, 4, 8, 12 and 24 h postoperatively. The usage of rescue antiemetics were similar in both groups of subjects.Conclusion The use of granisetron is comparable with the use of granisetron and dexamethasone in the prevention of PONV in parturients receiving intrathecal morphine for elective Caesarean section.

Pornpen Srisawasdi,1 Punyanuch Rodcharoen,1 Somlak Vanavanan,1 Anchalee Chittamma,1 Chonlaphat Sukasem,2 Chalitpon Na nakorn,2 Charungthai Dejthevaporn,3 Martin H Kroll4 1Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Quest Diagnostics, Secaucus, NJ 07094, United States of AmericaCorrespondence: Pornpen Srisawasdi Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Rama VI Road, Ratchathewi, Bangkok 10400, ThailandTel +66-2-201-0008Fax +66-2-354-7266Email srisawasdip@yahoo.comObjective: Patients treated with statins for dyslipidemia may still have a residual risk of atherosclerotic cardiovascular disease (ASCVD). To determine whether genetic variants in the cholesteryl ester transport protein (CETP), rs3764261 (C>A), rs708272 (G>A), and rs12149545 (G>A) affect ASCVD risk, we studied the association of these variants with dyslipidemia in statin-treated patients.Patients and Methods: We included 299 adult Thai patients treated with a statin (95 men and 204 women). Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. We used logistic regression models adjusted for potential confounders of age, body mass index, blood pressure, insulin resistance, and statin dosage to analyze the association between CETP variants and atherogenic lipoprotein patterns.Results: CETP polymorphisms of rs3764261 and rs708272, but not rs12149545, were significantly associated with high-density lipoprotein cholesterol (HDL-C), apoA-I, triglycerides, very low-density lipoprotein (VLDL)-C, and large LDL (LDL1-C) levels as well as mean LDL particle size (all p < 0.020). However, no significant difference was observed in total cholesterol, LDL-C, or apoB levels by CETP variants. Regardless of sex, the combination of rs3764261 (CC genotype) and rs708272 (GG or GA genotypes) showed a stronger association with atherogenic dyslipidemia, including features of decreased HDL-C, elevated triglycerides, and LDL subclass pattern B (odds ratio [OR] =  2.99, 95% confidence interval [CI]: 1.78– 5.02) compared with the single variant rs3764261 (OR =  2.11, 95% CI: 1.27– 3.50) or rs708272 (OR =  2.12, 95% CI: 1.29– 3.49).Conclusion: The polymorphisms of CETP rs3764261 (CC genotype) and rs708272 (GG and GA genotypes) may have a higher susceptibility to atherogenic dyslipidemia. Testing for CETP rs3764261 and rs708272 may serve as a surrogate marker for lipid management in statin-treated patients, which may help individualize treatment for reducing the residual risk of ASCVD.Keywords: residual atherosclerotic risk, statin treatment, cholesteryl ester transport protein, genetic polymorphisms, genetic risk

Abstract Background Polyglucosan body myopathy 1 (PGBM1) is a type of glycogen storage disease that can cause skeletal muscle myopathy and cardiomyopathy with or without immunodeficiency due to a pathogenic mutation in the RBCK1 gene. PGBM1 has been reported in only 14 European and American families, and no cognitive impairment phenotype was reported. Its prevalence in Asia is unknown. Case presentation: We report a Chinese boy with teenage onset of skeletal muscle myopathy and mild cognitive impairment. Whole-exome sequencing analysis identified a homozygous missense mutation in RBCK1 (c.1411G > A:p.Glu471Lys). A muscle biopsy indicated the accumulation of periodic acid-Schiff-positive material, which could be ubiquitinated by immunohistochemistry with an anti-ubiquitin antibody. In skeletal muscle tissue, HOIL-1 and HOIP protein levels were lower than those in the control, confirming the phenotype of an RBCK1 mutation. MRI revealed abnormal cerebral white matter signals. Immune system and cardiac examination found no abnormalities. The patient was diagnosed with PGBM1 with no effective treatment. Conclusions This case from China with a novel homozygous missense mutation in RBCK1 extends the phenotypic spectrum and geographical distribution of PGBM 1, which may cause cerebral white matter changes and cognitive impairment.

Notch is a cell–cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

Context Abortions damage the endometrium in women. Currently, therapeutic options for endometrial recovery are limited. Zishen Yutai Pill (ZYP) was found to promote endometrial blood supply as a traditional Chinese medicine. However, whether ZYP promotes endometrial recovery post-abortion has not yet been explored. Objective This study evaluated the role of ZYP in rat endometrial recovery after induced abortion and explored its mechanism of action. Materials and methods Sprague–Dawley rats were divided into three groups: no-operation group, control group, and ZYP group. The rats in the control and ZYP group were induced abortion, and then treated with normal saline or ZYPs, respectively, for 1–3 oestrous cycles. Morphological changes in the endometrium were examined. Expression levels of the factors related to endometrial recovery were analyzed. The duration of this study was almost seven months. Results The endometrial thickness (7.3 ± 0.17 mm) and number of glands (5.5 ± 0.20) increased significantly in the ZYP group compared with those in the control group (5.5 ± 0.15 mm and 3.5 ± 0.18; p

To reduce the computational complexity of scalar multiplication, an improved wNAF scalar-multiplication algorithm is proposed by using prime precomputation. It replaces odd number with prime number in the precomputation stage, and makes up the difference between prime and odd by building the tiny multi-base chains. Thanks to the proposed algorithm, the computational complexity, the cost of precomputation and the creation time of addition chains are all reduced. Compared with the wNAF, the computational complexity and the running speed are optimized by 28.37% and 77.38% respectively at the fittest case. Also, lower computational complexity and higher running speed are outstanding features of the introduced algorithm than other existing algorithms.

RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.

For acquisition of accurate aerodynamic parameters of the pipeline suspension bridge, the numerical wind tunnel model for the typical girder section of the oil and gas pipeline suspension bridge was built, and SST k-ε model was used as the numerical wind tunnel turbulence model. The bypass flow pressure field distribution acquired from the numerical wind tunnel shows that the negative pressure area on the upper and lower surfaces of the pipeline is obvious, the largest positive pressure area appears on the windward side of the pipeline, and the pressure difference between the windward side and the leeward side of the truss girder in the inflow direction is particularly obvious. The bypass flow velocity field distribution shows that the pipeline and truss girder exert significant blocking effect on the wind speed, and the flow separation and vortex shedding phenomena occur apparently on the pipeline, windward railings and truss girder. According to the root mean square pressure of the flow field, vortex vibration is most likely to occur in the inflow side truss. Through the analysis of the three component coefficients of different pipeline diameters and different girder widths at the wind attack angles of －3°, 0° and 3°, it is concluded that the girder width has little influence on resistance coefficient and lift coefficient, and the torsion coefficient decreases with the increase of the girder width at －3° wind attack angle. The pipeline diameter definitively influences the three component coefficients, that is, with the increase of pipeline diameter, the resistance coefficient increases gradually, while the lift coefficient and torsion coefficient decrease gradually. The research results are expected to provide wind-resistant data support for the design of suspension bridge deck structure and the piping layout.

Abstract Background Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans histiocytosis. Skeletal structures are affected in over 95% ECD patients. Due to the lack of proper imaging assessment tools, the alteration of bone microarchitecture in ECD has not been well studied. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a newly developed assessment of bone mineral density and bone microarchitecture. Methods We performed a cross-sectional study with 13 patients diagnosed with ECD in Peking Union Medical College Hospital between October 2018 and June 2019. The diagnosis of ECD was based on typical pathological findings in the context of appropriate clinical and radiological manifestations. Bone geometry, volumetric bone mineral density and bone microarchitecture of those ECD patients were assessed using HR-pQCT at the non-dominant distal radius and distal tibia. Those HR-pQCT parameters were then compared to an ongoing population-based database of HR-pQCT for Mainland Chinese. Results As a result, remarkable heterogeneity of osteosclerosis in the HR-pQCT images was found in ECD patients, ranging from apparent normal structure, scattered thickening of trabecula, to homogenous consolidation. In terms of quantitative measurements, total volumetric BMD (383.50 mg/cm3, 1.352 times of normal mean, p = 0.023) of the tibia differed significantly in ECD patients, due to the increased trabecular volumetric BMD (291 mg/cm3, 2.058 times of normal mean, p = 0.003). The increased trabecular volumetric BMD of tibia was associated with remarkably increased number of trabecula (1.7/mm, 1.455 times of normal mean, p = 0.002) and increased thickness of trabecula (0.37 mm, 1.466 times of normal mean, p = 0.003). These differences could be due to the existence of dense bone interposed in the trabecula. Conclusion This study is the first to assess the volumetric bone mineral density and bone microstructure with HR-pQCT in a cohort of ECD patients and indicated that the application of HR-pQCT may help to reveal the nature of bone lesions in the disease.

Kalopanax septemlobus is a deciduous medicinal tree species belonging to the family Araliaceae. It contains a number of triterpenoid saponins primarily constituted of hederagenin aglycones. Here, we presented de novo comparative transcriptome analysis using 454 pyrosequencing technology between embryogenic (EC) and nonembryogenic callus (NEC) of K. septemlobus. A total of 372,229 high-quality reads were generated by combining 168,065 EC reads and 204,164 NEC reads, which were then assembled into 80,280 and 63,128 unigenes, respectively. A comparative analysis of transcription profiles showed that 13,766 genes were differentially expressed between EC and NEC. Moreover, functional enrichment analysis revealed that a number of genes involved in the proteolysis and embryogenesis were highly expressed in EC, whereas oxidative stress-responsible genes were overpresented in NEC. Interestingly, the expression levels of genes involved in saponin biosynthesis, such as squalene epoxidase, cytochrome P450s, and glycosyl transferase, were also higher in NEC than in EC, suggesting that their expression is stress-inducible. In this study, we characterized the K. septemlobus transcriptome profiles involved in somatic embryogenesis (SE), which might enhance knowledge of SE process and provide a useful molecular resource for further study of K. septemlobus.

Objective To investigate the differences of spinal curvature, thoracic sagittal mobility, and respiratory strength between patients with chronic neck pain (CNP) and people without cervical pain, and to determine the correlation between respiratory strength and thoracic mobility in CNP patients. Methods A total of 78 participants were finally included in this study, of whom 30 had no cervical pain and 48 had CNP. The Neck Disability Index (NDI), cervical lordotic curvature, thoracic kyphotic curvature, thoracic sagittal range of motion (ROM), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured and analyzed. Results In males, thoracic sagittal ROMMEP-MIP and MEP showed a significant difference between the no cervical pain group and the CNP group. In females, thoracic kyphotic curvature, thoracic sagittal ROMMEP-MIP, MIP, and MEP were significantly different between the no cervical pain group and the CNP group. Thoracic kyphotic curvature was significantly correlated with MEP and MIP in all population groups, and significantly correlated with NDI in the female group. Thoracic sagittal ROMMEP-MIP had a significant linear relationship with NDI, MEP, and MIP in all population groups. Conclusion The thoracic mobility during forced respiration was reduced in patients with CNP and was correlated with respiratory strength. Changes in the biomechanics of the cervicothoracic spine and rib cage due to CNP may contribute to impairment of respiratory strength.

The aim of this study was to determine the effects of six common commercial lactic acid bacteria (LAB) additives [A1, Lactobacillus plantarum, L. buchneri, and Enterococcus faecalis; A2, L. plantarum and L. casei; A3, L. plantarum and L. buchneri; A4, L. plantarum, L. buchneri, L. casei, and Pediococcus acidilactici; A5, L. plantarum (producing feruloyl esterase); and A6, L. buchneri, P. acidilactici, β-glucanase, and xylanase] on the bacterial community and fermentation quality of alfalfa silage. Alfalfa was harvested at the squaring stage, wilted in the field for 24 h, and ensiled without any additives (Control) or with A1, A2, A3, A4, A5, or A6. Microbial counts, bacterial community, fermentation parameters, and nutritional composition were determined after ensiling for 90 days. The total abundance of LAB genera on alfalfa pre-ensiling was 0.38% in bacterial community. The abundances of Lactobacillus, Enterococcus, and Pediococcus in the Control silage were 42.18, 40.18, and 8.09% of abundance, respectively. The abundances of Lactobacillus in A1-, A2-, A3-, A4-, and A5-treatments were 89.32, 92.93, 92.87, 81.12, and 80.44%, respectively. The abundances of Pediococcus and Lactobacillus in A6-treatment were 70.14 and 24.86%, respectively. Compared with Control silage, LAB-treated silage had lower pH and less ammonia nitrogen and water-soluble carbohydrates concentrations (p < 0.05). Further, the A5- and A6-treatments contained lower neutral detergent fiber, acid detergent fiber, and hemicellulose than other treatments (p < 0.05). Overall, LAB genera were presented as minor taxa in alfalfa pre-ensiling and as dominant taxa in alfalfa silage. Adding LAB additives improved the fermentation quality and altered the bacterial community of alfalfa silage. The main bacterial genera in Control silage were Lactobacillus, Enterococcus, and Pediococcus. Lactobacillus dominated the bacterial communities of A1-, A2-, A3-, A4-, and A5-treatments, while Pediococcus and Lactobacillus were dominant bacterial genera in A6-treatment. Inoculating A5 and A6 degraded the fiber in alfalfa silage. It is necessary to ensile alfalfa with LAB inoculants.

Objectives Our study aimed to investigate the relationship between the severity of frailty and the long-term care (LTC) needs of older adults from Chinese communities.Design A cross-sectional study.Setting Three Chinese community health centres. All data were collected by trained researchers through face-to-face collection.Participants We surveyed a total of 540 older residents who aged 60 or older from community in Guangzhou, China.Measures The Chinese version of the Tilburg frailty indicator was used to assess the frailty status of participants. LTC needs was evaluated by Integrated Home Care Services Questionnaire. Using non-adjusted and multivariate adjusted logistic regression analysis to evaluate frailty and LTC needs, then smoothed plots, threshold effect analysis and P for trend were used to further investigate the relationship between them.Results The prevalence of frailty was 45.2% among the 540 older adults enrolled (aged 70.4±8.3 years; 65.7% females). 27% had higher LTC needs, which increased to 65.1% for individuals with frailty. Logistic regression analysis showed that frailty was strongly associated with LTC needs (OR 3.06, 95% CI 2.06 to 4.55, p

A 47-year-old female with cardiac dysfunction and lymphadenopathy underwent 18FDG PET/CT and 68Ga-FAPI-04 imaging for tumor screening. Mild uptake in the left ventricular wall was detected on the oncology 18FDG PET/CT. True myocardiac-involvement could not be distinguished with physiological uptake. The following 68Ga-FAPI-04 showed intense heterogeneous uptake in the left ventricular wall, particularly in the septum and apex area, corresponding with the late gadolinium enhancement regions shown by cardiac MR. Intense uptake was also noted in the mediastinal and bilateral hilar lymph nodes. Endomyocardial biopsy demonstrated sarcoidosis.

This study aimed to reveal the bacterial community and fermentation quality of Leymus chinensis silage during the fermentation process. L. chinensis was harvested at the heading stage, and ensiled with lactic acid bacteria (LAB, L), water (W), or a combination of both (LW) in vacuum-sealed plastic bags. As a control silage, untreated L. chinensis silage was also assessed. The samples were taken at 0, 5, 15, 35, and 60 days after ensiling. The bacterial community structure was assessed by plate cultivation and Illumina sequencing, and the fermentation parameters were also analyzed. Fresh L. chinensis contained low moisture (509 g/kg) and LAB (3.64 log colony-forming units/g fresh weight). Control silage displayed higher pH and lower lactic acid (LA) than other treatments during ensilage (p < 0.05); moreover, LW-treatment had lower pH from 5 to 35 days and greater LA at 5 days than L- and W-treatments (p < 0.05). During the fermentation process, Lactobacillus in L- and LW-treatments was the most dominant bacterial genus (>97%), had higher abundance than that in control silage and W-treatment (p < 0.05), and correlated negatively with other main genera and pH, and positively with LA and acetic acid (p < 0.05). Moreover, Lactobacillus had considerable abundance in W-treatment from 5 to 15 days (81.38–85.86%). Enterobacteriaceae had the most abundance among bacteria in control silage during ensiling (49.31–69.34%), and in W-treatment from 35 to 60 days (47.49–54.15%). The L-, W-, and LW-treatments displayed the aggregated bacterial community at 5 and 15 days, with W-treatment diverging from L- and LW-treatments at 35 and 60 days. Overall, the low moisture and/or insufficient LAB in fresh L. chinensis led to Enterobacteriaceae dominating bacterial community and contributing to the high pH and low LA in control silage during the fermentation process. Applying L, W, or LW contributed to Lactobacillus succession, LA production, and pH reduction during early stage of fermentation; moreover, treating with L and LW displayed more efficiency. Lactobacillus dominated the entire ensilage process in L- and LW-treatments and the early stage of fermentation in W-treatment, and contributed to the satisfactory fermentation quality of L. chinensis silage. The L- and LW-treatments displayed a similar pattern of bacterial succession during ensiling.

Background: Zishen Guchong Pill (ZGP), a traditional oriental herbal medicine, has been applied broadly in the treatment of threatened or recurrent miscarriages in clinics, but little is known about its developmental toxicity.Aim of the study: This study aimed to investigate the potential toxicity of ZGP and its mechanisms.methods: We investigated the developmental toxicity of ZGP using a zebrafish model. Zebrafish embryos at 4 hours post-fertilization (hpf) were exposed to 25, 50, 100, and 200 µg/mL ZGP until 120 hpf. The zebrafish morphology, organ development, reactive oxygen species (ROS) content, oxidative stress-related enzyme activity, and mRNA levels of oxidative stress and apoptosis-related genes were measured.Results: Our results demonstrated that ZGP had no toxicity at 50 µg/mL ZGP but induced phenotypic defects and decreased the hatching rate and body length at more than 50 µg/mL ZGP (high dose). High doses of ZGP caused severe heart failure, including a significant increase in the sinus venosus (SV) and bulbus arteriosus (BA) distance and pericardial area, and reduced heart rate and numbers of red blood cells. In addition, high doses of ZGP caused liver atrophy and decreased the length of dopamine ganglia and neurovascular. High doses of ZGP elicited the generation of ROS and elevated malondialdehyde levels, but reduced the activity of superoxide dismutase (SOD) and catalase (CAT). Real-time PCR data showed the downregulation of oxidative stress-related genes (sod and cat) and the activation of Nrf2 (nrf2, keap1, ho-1, nqo1, gclc, and gclm) and P53 (p53, bcl-2, and bax) signal pathway genes after high ZGP exposure.Conclusions: Taken together, our results indicate that ZGP has no developmental toxicity under 50 µg/mL ZGP but induced developmental toxicity in zebrafish embryos at more than 50 µg/mL ZGP, and oxidative stress contributed to the toxic response. • ZGP is safe and reliable in clinical use. • ZGP (high does) caused an increase in ROS, which induced oxidative stress, leading to apoptosis and developmental toxicity. • The Nrf2 signaling pathway is impaired during the early stages of ZGP-induced developmental toxicity.

Microtubules play a fundamental role in plant development, morphogenesis, and cytokinesis; they are assembled from heterodimers containing an α-tubulin (TUA) and a β-tubulin (TUB) protein. However, little research has been conducted on the TUA and TUB gene families in hexaploid wheat (Triticum aestivum L.). In this study, we identified 15 TaTUA and 28 TaTUB genes in wheat. Phylogenetic analysis showed that 15 TaTUA genes were divided into two major subfamilies, and 28 TaTUB genes were divided into five major subfamilies. Mostly, there were similar motif compositions and exon-intron structures among the same subfamilies. Segmental duplication of genes (WGD/segmental) is the main process of TaTUA and TaTUB gene family expansion in wheat. It was found that TaTUA and TaTUB genes presented specific temporal and spatial characteristics based on the expression profiles of 17 tissues during wheat development using publicly available RNA-seq data. It was worth noting, via qRT-PCR, that two TaTUA and five TaTUB genes were highly expressed in fertile anthers compared to male sterility. These were quite different between physiological male sterile lines and S-type cytoplasmic male sterile lines at different stages of pollen development. This study offers fundamental information on the TUA and TUB gene families during wheat development and provides new insights for exploring the molecular mechanism of wheat male sterility.

Near-infrared-excited upconversion nanoparticles (UCNPs) have multicolor emissions, a low auto-fluorescence background, a high chemical stability, and a long fluorescence lifetime. The fluorescent probes based on UCNPs have achieved great success in the analysis of different samples. Here, we presented the research results of UCNPs probes utilized in analytical applications including environment, biology, food and medicine in the last five years; we also introduced the design and construction of upconversion optical sensing platforms. Future trends and challenges of the UCNPs used in the analytical field have also been discussed with particular emphasis.

Background: Dyspnea is a multidimensional experience similar to pain and is one of the most common clinical presentations in patients with respiratory diseases. Accurately evaluating the experience of dyspnea allows nurses and physicians to deliver better medical services to patients. The multidimensional dyspnea profile emphasizes the psychosocial factors of dyspnea and assesses immediate discomfort, sensory qualities, and the emotional responses of patients with dyspnea. At present, the validity, reliability, and test–retest reliability of the multidimensional dyspnea profile in patients with respiratory diseases in China are unclear. Objectives: The aim of this study was to investigate the validity, reliability, and test–retest reliability of the Chinese version of the multidimensional dyspnea profile and to assess the convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale. Methods: The factorial construct, intraclass correlations, internal consistency, and convergent validity of the Chinese version of the multidimensional dyspnea profile was evaluated using data from 231 inpatients with dyspnea from the respiratory department of a hospital. In the principal component analysis stage, 131 inpatients were evaluated. In the test–retest reliability analysis stage, 50 out of the 131 patients responded to the questionnaire again. In the confirmatory factor analysis, 100 inpatients from an independent sample were assessed. Results: The principal component analysis showed that the Chinese version of the multidimensional dyspnea profile had a two-factor structure: the immediate perceptual-related problem factor (6 items) and the emotional response-related problem factor (5 items). The convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale was significant and acceptable based on the average variance extracted (r = .56, p

A novel wideband filtering dumbbell-shaped slot antenna with improved frequency selectivity for both band-edges is proposed in this paper. The filtering slot antenna is composed of a dumbbell-shaped slot, two parasitic patches, eight slot-stubs and a feeding line with a pair of step impedance resonator (SIR) stubs. An additional resonance is generated to increase the bandwidth and a gain null is produced at the upper band-edge to improve the frequency selectivity by loading parasitic patches in the dumbbell-shaped slot. Eight slot-stubs adjacent to the dumbbell-shaped slot are etched to enhance the impedance matching. In addition, the bandwidth is further broadened and two gain nulls are realized at both band-edges by adding a pair of SIR stubs. Moreover, the gain nulls can be adjusted individually by the length of parasitic patches or SIR stubs. As a result, the gain curve of the proposed filtering slot antenna has good flatness and the frequency selectivity for both band-edges is significantly improved. A prototype has been manufactured and measured to verify the validity of the design. The measured impedance bandwidth of |S11|

Brown adipose tissue (BAT) is important in monitoring energy homeostasis and cancer cachexia. Different from white adipose tissue, BAT is characterized by the presence of a large number of mitochondria in adipocytes. Translocator protein 18 kDa (TSPO), a critical transporter, is expressed in the outer membrane of mitochondria. We speculated that [18F]DPA714, a specific TSPO tracer, may monitor BAT activity in tumor-bearing mice in vivo. We first analyzed the radioactive uptake of positron emission tomography (PET) tracers in BAT of CT26 xenograft mice with 18F-fluorodeoxyglucose ([18F]FDG) and [18F]DPA714. We also studied the BAT uptake of [18F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [18F]FDG is quite variable among animals, even in mice of the same tumor model (%ID/g-mean: mean ± SDM, 8.61 ± 8.90, n = 16). Contrarily, [18F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [18F]DPA714 in BAT was significantly higher on day 26 than that on day 7 in CT26 xenograft model. Taken together, these results strongly indicate the potential feasibility of [18F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.

Background: The increasing amount of sewage sludge (SS) and more legislative regulation of its disposal have stimulated the need for developing new technologies including gamma irradiation to recycle SS efficiently. Objective: To evaluate the effects of gamma irradiated and non-irradiated SS (SSGI and SSNI, respectively) on essential oil (EO) content and composition of Ocimum basilicum L. Methods: A greenhouse experiment was conducted with 15, 30, and 60 g kg-1 of SS irradiated with absorbed doses of 5, 10, and 20 kGy gamma-ray and soil without SS and irradiation as the control treatment. The essential oil was isolated by hydro-distillation and analyzed by Gas chromatography and Gas chromatography-mass spectrometry techniques. Results: The applications of SSGI and SSNI at all levels except 15 g kg-1 significantly enhanced EO content compared to the control. The using of 60 g kg-1 SS in each absorbed dose significantly reduced EO yield relative to the control, while it was significantly increased under 15 and 30 g kg-1 SSNI and SSGI. Also, in 60 g SS kg-1, the restriction effects on EO yield were mitigated with increasing the absorbed dose of gamma-ray, but it was insignificant with increasing absorbed dose to 10 and 20 relative to 5 kGy. The methyl chavicol as a major constituent of EO was significantly increased in SSGI and SSNI as compared with the control. However, the increment in the methyl chavicol content was not significant between the treatments ≥ 30 g kg-1 SSGI or SSNI and 15 g kg-1 SS at absorbed dose of ≥10 kGy. 98 Conclusion: To improve essential oil content and composition, application of ≤ 30 g kg-1 sewage sludge with 5 kGy absorbed dose of gamma-ray can be suggested at similar conditions.

Apichaya Puangpetch,1 Pornpen Srisawasdi,2 Weerapon Unaharassamee,3 Napa Jiratjintana,3 Somlak Vanavanan,2 Suweejuk Punprasit,2 Chalitpon Na Nakorn,1 Chonlaphat Sukasem,1 Martin H Kroll41Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Psychiatry, Somdet Chaopraya Institute of Psychiatry, Bangkok, Thailand; 4Quest Diagnostics, Secaucus, NJ 07094, USAObjective: To determine whether genetic polymorphisms related to pharmacodynamics with metabolic adverse effects, namely leptin promoter (LEP) rs7799039, leptin receptor rs1137101, dopamine D2 rs4436578, serotonin 5-HT2A rs6313, and serotonin 5-HT2C rs518147 and rs12836771, are associated with hyperglycemia induced by risperidone or clozapine in adult Thai patients with psychosis.Methods: A total of 180 patients treated with risperidone-based (n=130) or clozapine-based (n=50) regimens were included in this study. Blood samples were analyzed for genotyping of the candidate genes and biochemical testing. Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis.Results: The prevalence of hyperglycemia was higher in patients receiving clozapine (64.0%) than in those receiving risperidone (30.8%). Among the candidate genes, only the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia (χ2=9.879, P=0.008) in patients treated with risperidone; patients with the AA genotype had the highest risk (41.1%), followed by those with AG (20.8%) and GG (0%) genotypes. Using the recessive genetic model (AA vs AG + GG), the odds ratio and 95% CI were 3.28 and 1.44 −7.50, respectively. None of the genes were associated with hyperglycemia in patients treated with clozapine. A binary logistic regression revealed that the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia, independent of body-mass index (BMI) in patients receiving risperidone; the odds ratio (95% CI) was 3.188 (1.399–7.262), P=0.006. By contrast, none of the pharmacodynamic genetic factors, except for BMI, were significantly associated with hyperglycemia in patients receiving clozapine.Conclusion: The risk of type 2 diabetes mellitus is associated with the LEP rs7799039 polymorphism in Thai adults receiving risperidone but not in those receiving clozapine. Clarifying underlying mechanisms and risk of hyperglycemia provides an opportunity to prevent impaired glucose metabolism in patients receiving risperidone or clozapine.Keywords: atypical antipsychotics, leptin promoter, leptin receptor, dopamine D2, serotonin 5-HT2A, serotonin 5-HT2C, diabetes mellitus

Abstract Background DUOII is a multi-ovary wheat (Triticum aestivum L.) line with two or three pistils and three stamens in each floret. The multi-ovary trait of DUOII is controlled by a dominant gene, whose expression can be suppressed by the heterogeneous cytoplasm of TeZhiI (TZI), a line with the nucleus of common wheat and the cytoplasm of Aegilops. Crosses between female DUOII plants and male TZI plants resulted in multi-ovary F1s; whereas, the reciprocal crosses resulted in mono-ovary F1s. Although the multi-ovary trait is inherited as single trait controlled by a dominant allele in lines with a Triticum cytoplasm, the mechanism by which the special heterogeneous cytoplasm suppresses the expression of multi-ovary is not well understood. Results Observing the developmental process, we found that the critical stage of additional pistil primordium development was when the young spikes were 2–6 mm long. Then, we compared the quantitative proteomic profiles of 2–6 mm long young spikes obtained from the reciprocal crosses between DUOII and TZI. A total of 90 differentially expressed proteins were identified and analyzed based on their biological functions. These proteins had obvious functional pathways mainly implicated in chloroplast metabolism, nuclear and cell division, plant respiration, protein metabolism, and flower development. Importantly, we identified two key proteins, Flowering Locus K Homology Domain and PEPPER, which are known to play an essential role in the specification of pistil organ identity. By drawing relationships between the 90 differentially expressed proteins, we found that these proteins revealed a complex network which is associated with multi-ovary gene expression under heterogeneous cytoplasmic suppression. Conclusions Our proteomic analysis has identified certain differentially expressed proteins in 2–6 mm long young spikes, which was the critical stage of additional primordium development. This paper provided a universal proteomic profiling involved in the cytoplasmic suppression of wheat floral meristems; and our findings have laid a solid foundation for further mechanistic studies on the underlying mechanisms that control the heterogeneous cytoplasm-induced suppression of the nuclear multi-ovary gene in wheat.

Abstract Studies have shown that a normal circadian rhythm is crucial to learning and memory. Circadian rhythm disturbances that occur at early stages of Alzheimer’s disease (AD) aggravate the progression of the disease and further reduce learning and memory in AD patients. The novel, dual GLP-1R/GIPR agonist DA-JC1 has been found to exert a stronger hypoglycemic effect than a GLP-1R agonist alone and has been shown to exert neuroprotective effects. However, it is not clear whether DA-JC1 improves the Aβ31–35-induced decline in learning and memory ability by restoring disrupted circadian rhythms. In the present study, we carried out a mouse wheel-running experiment and Morris water maze test (MWM) and found that DA-JC1 could effectively improve the decline of learning and memory and circadian rhythm disorders induced by Aβ31–35. After downregulating Per2 expression via lentivirus-shPer2 in the hippocampus and the hippocampal HT22 cells, we found that circadian rhythm disorders occurred, and that DA-JC1 could not improve the impaired learning and memory. These results suggest that DA-JC1 improves damage to learning and memory by antagonizing circadian rhythm disorders induced by Aβ31–35. The outcome of this ongoing study may provide a novel therapeutic intervention for AD in the future.

Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery of resveratrol was achieved by conjugating resveratrol to triphenylphosphonium (TPP). The anti-cancer effects of TPP-resveratrol were studied in the murine breast cancer 4T1 and the human breast cancer MDA-MB-231 cell lines. Flow cytometry was used to study apoptosis induction, cell cycle arrest, and mitochondrial membrane potential loss. The morphological changes in the mitochondria in MDA-MB-231 cells after TPP-resveratrol treatments were examined using transmission electron microscopy. Moreover, the changes in MDA-MB-231 cell metabolism after resveratrol and TPP-resveratrol treatments were studied using metabolomic analysis. We demonstrate that TPP-resveratrol significantly improved cytotoxicity in 4T1 cells and MDA-MB-231 cells by inducing apoptosis and mitochondrial membrane potential loss. Swollen and vacuolated mitochondria were observed after the TPP-resveratrol treatment. Meanwhile, TPP-resveratrol treatment down-regulated amino acid and energy metabolism and caused the dysfunction of purine and pyrimidine metabolism. Our results provide evidence supporting the targeted delivery of resveratrol to mitochondria and suggest that TPP-resveratrol may be an effective agent for breast cancer treatment.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, “Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial.” Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

The study was aimed to investigate the effect of moisture content on microbial communities, metabolites, fermentation quality, and aerobic stability during aerobic exposure in whole-plant corn silages preserved long time to improve the quality and aerobic stability of the silage during feed-out. Corn plants with two different moisture levels (high-moisture content, 680 g/kg; low-moisture content, 620 g/kg) were harvested at one-third and two-thirds milk-line stages, respectively, ensiled in laboratory-scale silos, and then sampled at 350 day after ensiling and at 2 and 5 day after opening to investigate bacterial and fungal communities, metabolites, and aerobic stability. High-moisture content increased aerobic stability and pH and decreased lactic acid and microbial counts in silages (P < 0.05). During aerobic exposure, the low-moisture silages had higher pH and lactic acid bacterial count and lower lactic acid than the high-moisture silages (P < 0.05); Acinetobacter sp. was the most main bacterial species in the silages; Candida glabrata and unclassified Candida had an increasing abundance and negatively correlation with aerobic stability of high-moisture silages (P < 0.05), while C. glabrata, Candida xylopsoci, unclassified Saccharomycetaceae, and unclassified Saccharomycetales negative correlated with aerobic stability of low-moisture silages (P < 0.05) with a rising Saccharomycetaceae; the silages had a reducing concentration of total metabolites (P < 0.05). Moreover, the high-moisture silages contained greater total metabolites, saturated fatty acids (palmitic and stearic acid), essential fatty acids (linoleic acid), essential amino acids (phenylalanine), and non-essential amino acids (alanine, beta-alanine, and asparagine) than the low-moisture silages at 5 day of opening (P < 0.05). Thus, the high-moisture content improved the aerobic stability. Acinetobacter sp. and Candida sp. dominated the bacterial and fungal communities, respectively; Candida sp. resulted in the aerobic deterioration in high-moisture silages, while the combined activities of Candida sp. and Saccharomycetaceae sp. caused the aerobic deterioration in low-moisture silages. The greater aerobic stability contributed to preserve the palmitic acid, stearic acid, linoleic acid, phenylalanine, alanine, beta-alanine, and asparagine during aerobic exposure.

BackgroundHyperhomocysteinemia (HHcy) causes cardiovascular diseases via regulating inflammatory responses. We investigated whether and how the epithelial sodium channel (ENaC), a recently identified ion channel in endothelial cells, plays a role in HHcy-induced endothelial dysfunction.MethodsCell-attached patch-clamp recording in acute split-open aortic endothelial cells, western blot, confocal imaging, and wire myograph combined with pharmacological approaches were used to determine whether HHcy-mediated inflammatory signaling leads to endothelial dysfunction via stimulating ENaC.ResultsThe data showed that 4 weeks after L-methionine diet the levels of plasma Hcy were significantly increased and the ENaC was dramatically activated in mouse aortic endothelial cells. Administration of benzamil, a specific ENaC blocker, ameliorated L-methionine diet-induced impairment of endothelium-dependent relaxation (EDR) and reversed Hcy-induced increase in ENaC activity. Pharmacological inhibition of NADPH oxidase, reactive oxygen species (ROS), cyclooxygenase-2 (COX-2)/thromboxane B2 (TXB2), or serum/glucocorticoid regulated kinase 1 (SGK1) effectively attenuated both the Hcy-induced activation of endothelial ENaC and impairment of EDR. Our in vitro data showed that both NADPH oxidase inhibitor and an ROS scavenger reversed Hcy-induced increase in COX-2 expression in human umbilical vein endothelial cells (HUVECs). Moreover, Hcy-induced increase in expression levels of SGK-1, phosphorylated-SGK-1, and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (p-Nedd4-2) in HUVECs were significantly blunted by a COX-2 inhibitor.ConclusionWe show that Hcy activates endothelial ENaC and subsequently impairs EDR of mouse aorta, via ROS/COX-2-dependent activation of SGK-1/Nedd4-2 signaling. Our study provides a rational that blockade of the endothelial ENaC could be potential method to prevent and/or to treat Hcy-induced cardiovascular disease.

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47phox, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell–expressed developmentally downregulated protein 4–2 (p-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß-, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H2S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.