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The frequency of percutaneous transluminal angioplasty (PTA) procedures has substantially increased, but its effect on vascular access recreation (VAR) remains inconclusive. We conducted a population-based retrospective analysis of Taiwan hemodialysis (HD) centers from 2004 to 2012. Data was accumulated into center-level characteristics, including patients' demographics, baseline characteristics, PTA procedures, and VAR. Center-level characteristics were summarized annually using appropriate measures. A mixed model assessed the association between PTA frequency and VAR rates, considering within-center correlation and adjusting for potential confounders. A total of 82,005 patients (mean age 62.7 ± 13.9 years, 50.5% male, 48.5% with diabetes mellitus) from 820 HD centers were analyzed. From 2004 to 2012, PTA frequency significantly increased from 1.24 to 3.23 per 1000 HD sessions, while VAR rates did not decline as expected (0.5–0.8 per 1000 HD sessions). Compared with the HD centers of infrequent use of PTA (annual lowest quartile, range 0.39–1.20 per 1000 HD sessions), the ones of frequent use (annual highest quartile, range 2.52–5.10 per 1000 HD sessions) didn't have lower VAR (range 0.54–0.99 vs. 0.50–0.91 per 1000 HD sessions, respectively). After controlling the potential confounders, the HD centers' PTA rates were not significantly associated with lower VAR rates (− 2.6, 95% confidence interval: − 30.3; 25.0, p = 0.85). Frequent use of PTA does not seem to improve VA patency at the center level, with no significant association identified with lower VAR. The indication of PTA in daily practice should be re-evaluated in terms of its efficiency in lowering VAR. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the in vitro tolerance to decentration of biaspheric intraocular lens (IOLs) with refractive phase-ring extended depth-of-focus (EDOF) and diffractive trifocal designs. Methods: This experimental study was carried out at the Department of Optics and Optometry and Vision Science, University of Valencia, Spain. The modulation transfer function (MTF) of the ETLIO130C EDOF and the TFLIO130C trifocal IOLs (AST Products Inc., Billerica, MA, USA) were determined at different levels of decentration for a given wavelength and pupil diameter using the PMTF optical bench (Lambda-X Ophthalmics, Nivelles, Belgium). The modulation transfer function (MTF) curves, the through-focus MTF curves, and the Strehl ratios were measured at 3-mm pupil aperture for 0.25-, 0.50- and 0.75-mm decentration. Results: The optical design of the trifocal TFLIO130C IOL is robust to small decentrations, with virtually no change in MTF response for 0.25 mm decentration. For greater decentration levels, the MTF response is slightly reduced with increasing decentration. The ETLIO130C EDOF design is robust to decentration, as the MTF response is only minimally affected when increasing the decentration up to 0.75 mm. Conclusions: MTF responses are slightly reduced with greater levels of decentration, but the range of focus provided by both trifocal and EDOF designs are preserved. The effects for average levels of decentration reported in the literature are minimum for both IOL designs. [ABSTRACT FROM AUTHOR]

Coral polyps are composed of four tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of tentacles (Te), mesenterial filaments (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. This dataset and new insights into tissue functions will facilitate a deeper understanding of symbiotic biology, immunology, biomineralization, digestive biology, and neurobiology in corals. A draft genome and tissue-specific transcriptome assemblies of the large-polyp coral, Fimbriaphyllia ancora were established. This dataset and new insights into tissue functions will facilitate a deeper understanding of coral biology. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a dynamic process enabling polarized epithelial cells to acquire mesenchymal features implicated in development and carcinoma progression. As our understanding evolves, it is clear the reversible execution of EMT arises from complex epigenomic regulation involving histone modifications and 3-dimensional (3D) genome structural changes, leading to a cascade of transcriptional events. This review summarizes current knowledge on chromatin organization in EMT, with a focus on hierarchical structures of the 3D genome and chromatin accessibility changes. A Mini Review summarizing the current understanding of epithelial-mesenchymal transition (EMT) and 3D genome organization, focusing on the role of chromatin conformation and accessibility changes during the transitional phases of EMT. [ABSTRACT FROM AUTHOR]

COVID-19 has been a significant global concern due to its contagious nature. In May 2021, Taiwan experienced a severe outbreak, leading the government to enforce strict Pandemic Alert Level 3 restrictions in order to curtail its spread. Although previous studies in Taiwan have examined the effects of these measures on air quality, further research is required to compare different time periods and assess the health implications of reducing particulate matter during the Level 3 lockdown. Herein, we analyzed the mass concentrations, chemical compositions, seasonal variations, sources, and potential health risks of PM1.0 and PM2.5 in Central Taiwan before and during the Level 3 lockdown. As a result, coal-fired boilers (47%) and traffic emissions (53%) were identified as the predominant sources of polycyclic aromatic hydrocarbons (PAHs) in PM1.0, while in PM2.5, the dominant sources of PAHs were coal-fired boilers (28%), traffic emissions (50%), and iron and steel sinter plants (22.1%). Before the pandemic, a greater value of 20.9 ± 6.92 μg/m3 was observed for PM2.5, which decreased to 15.3 ± 2.51 μg/m3 during the pandemic due to a reduction in industrial and anthropogenic emissions. Additionally, prior to the pandemic, PM1.0 had a contribution rate of 79% to PM2.5, which changed to 89% during the pandemic. Similarly, BaPeq values in PM2.5 exhibited a comparable trend, with PM1.0 contributing 86% and 65% respectively. In both periods, the OC/EC ratios for PM1.0 and PM2.5 were above 2, due to secondary organic compounds. The incremental lifetime cancer risk (ILCR) of PAHs in PM2.5 decreased by 4.03 × 10-5 during the pandemic, with PM1.0 contributing 73% due to reduced anthropogenic activities. [ABSTRACT FROM AUTHOR]

Pancreatic fluid collections (PFCs) including pancreatic pseudocyst (PP) and walled-off necrosis (WON) are complications after acute pancreatitis. We aimed to evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided lumen-apposing metal stent (LAMS) placement to manage PFCs. Between June 2019 and May 2023, patients with symptomatic PFCs who underwent EUS-guided electrocautery-enhanced LAMS drainage were enrolled retrospectively from eight tertiary centers in Taiwan. In total, 33 [14 (42.42%) PP and 19 (57.58%) WON] patients were enrolled. Gallstones (27.27%) and abdominal pain (72.73%) were the most common etiology and indication for drainage. The technical and clinical success rates were 100% and 96.97%, respectively, and the mean procedure time was 30.55 (± 16.17) min. Complications included one (3.03%) case of self-limited bleeding; there were no cases of mortality. Seven (21.21%) patients had recurrence. Patients with disconnected pancreatic duct syndrome (DPDS) had a higher recurrence rate than those without (71.43% vs. 38.46%, p = 0.05). After replacing LAMSs with transmural double-pigtail plastic stents (DPSs) in the DPDS patients, the DPS migration rate was higher in the patients with recurrence (100% vs. 33.33%, p = 0.04). In conclusion, drainage of symptomatic PFCs with EUS-guided electrocautery-enhanced LAMS appears to be efficient and safe. Replacing LAMSs with DPSs in DPDS patients was associated with a lower recurrence rate. [ABSTRACT FROM AUTHOR]

Gift-giving consumption is an important part of household consumption and is closely linked to people's welfare, particularly in rural China. By employing data from the China Family Panel Studies, this study investigates whether and how household gift-giving consumption affects subjective well-being in rural China. The findings suggest that such consumption has a significant and positive effect on the subjective well-being of rural residents in China, and social trust mediates the relationship between household gift-giving consumption and subjective well-being. Furthermore, the study conducts a robustness analysis based on various age and income groups, and the results demonstrate that gift-giving consumption has a significant positive effect on the subjective well-being of younger people, but no significant effect on the subjective well-being of middle-aged and elderly people. In addition, household gift-giving consumption significantly improves the subjective well-being of low-income people in rural China, but it does not have a statistically significant effect on high-income people. The findings of this study have some implications for policymakers. [ABSTRACT FROM AUTHOR]

As information technology develops rapidly and network information becomes more and more transparent, it is urgent for airlines to increase their flight carrying rates through marketing to maximize profits before take-off. While the seat bidding strategy has been one of the business models adopted by many airlines in recent years, it has not been implemented yet in Taiwan's airlines. In order to understand the seat bidding behavior of passengers, this study adopted the double-hurdle model to explore the factors affecting passengers' participation in seat bidding and calculated the prices they were willing to pay. Moreover, this study investigated the effects of long and short flight distances on passengers' participation in seat bidding and the prices they were willing to pay for either flight distance. According to the results, the factors affecting the participation of passengers in seat bidding were different for long-distance and short-distance trips, while a common factor between them was that young people and passengers with preliminary knowledge of such activities were more willing to participate. According to the analysis on the prices people were willing to pay, the price difference that passengers of long-haul flights and short-haul flights were willing to pay for upgrades was about 55 and 24% of the reference price, respectively. The information obtained in this study can serve as a reference for future research or for airlines. [ABSTRACT FROM AUTHOR]

Acetone is solvent widely used in laboratories and factories. Serious problems will occur when it is exposed to the environment. Therefore, a new design for a bimetallic metal functional group catalyst that can convert acetone into carbon dioxide and water within 250 °C was prepared, in order to effectively treat acetone and reduce the required energy. Hydrophobic Y type zeolite adsorption and low-temperature catalytic combustion were used to continuously treat acetone, and the effect of different operating parameters (including different metal loads, metal content, transformation temperature, pollutant concentration, and space velocity) on the efficiency of acetone treatment was discussed in this study. The isothermal adsorption model, kinetics, and thermodynamic model analysis were also used to establish the reaction mechanism, and to explore the factors affecting the catalyst reaction rate. The results show that the acetone conversion rate of 10-Fe1Mn1-USY reaches 90% at 400 ppm, 20,000 h−1 space velocity, and 227 °C. The kinetic behavior of the reaction between 10-Fe1Mn1-USY and acetone is more suited to the Power-rate Law model. Arrhenius equation analysis results show that the required activation energy for the reaction between 10-Fe1Mn1-USY and acetone is 70.2 kJ mol−1, and the collision frequency factor is 2.81 × 105 s−1. This reaction is an endothermic reaction, and the main reaction mechanism is surface metal oxidation. A new design for a bimetallic metal functional group catalyst that can convert acetone into carbon dioxide and water within 250 ℃ was prepared, in order to effectively treat acetone and reduce the required energy. Hydrophobic Y type zeolite adsorption and low-temperature catalytic combustion were used to continuously treat acetone, and the effect of different operating parameters on the efficiency of acetone treatment was discussed in this study. Result shown that the redox reaction between the adsorbed acetone and the active oxygen on the surface of the catalyst to generate CO2 and H2O. [ABSTRACT FROM AUTHOR]

Due to the ecological importance of mutualism between reef-building corals and symbiotic algae (Family Symbiodiniaceae), various transcriptomic studies on coral-algal symbiosis have been performed; however, molecular mechanisms, especially genes essential to initiate and maintain these symbioses remain unknown. We investigated transcriptomic responses of Acropora tenuis to inoculation with the native algal symbiont, Symbiodinium microadriaticum, during early life stages, and identified possible symbiosis-related genes. Genes involved in immune regulation, protection against oxidative stress, and metabolic interactions between partners are particularly important for symbiosis during Acropora early life stages. In addition, molecular phylogenetic analysis revealed that some possible symbiosis-related genes originated by gene duplication in the Acropora lineage, suggesting that gene duplication may have been the driving force to establish stable mutualism in Acropora, and that symbiotic molecular mechanisms may vary among coral lineages. Investigation of the transcriptomic responses of Acroporatenuis to inoculation with the native algal symbiont identifies genes that may support coral-algal symbiosis during early life stages of corals. [ABSTRACT FROM AUTHOR]

Leisure time physical activity (LTPA) has been frequently reported as a method of improving happiness. However, the effects of LTPA sufficiency and age differences in adults have been less discussed in the literature. The aim of this study was to examine the relationship between LTPA sufficiency and happiness based on an age stratification perspective. A total of 16,412 data observations from the Taiwanese Physical Activity Annual Survey (PAAS) were used for this study. Multivariate logistic regression analyses were applied to examine the odds ratio of the LTPA-sufficient population on happiness. The odds of happiness were 2.5–3 times higher among LTPA-sufficient young adults (25–29 years old) than among the insufficient group. However, unexpectedly, a negative association was observed between sufficient LTPA and happiness in 35- to 39-year-old men. Intrapersonal differences (e.g., achievement goals and motivational level) and the environment (social context) might play a fundamental role in the LPTA-happiness relationship. Sufficient LTPA was associated with increased happiness among Taiwanese adults. However, the relationships between sufficient LTPA and happiness were not consistent when stratified by age. Further research on the relevant mechanism underlying this phenomenon is warranted. Trial registration: This study was approved by the Institutional Review Board of Chung Shan Medical University Hospital (CRREC-104-015), registered on 18 October 2016. [ABSTRACT FROM AUTHOR]

AXL is a receptor tyrosine kinase that is often overexpressed in cancers. It contributes to pathophysiology in cancer progression and therapeutic resistance, making it an emerging therapeutic target. The first-in-class AXL inhibitor bemcentinib (R428/BGB324) has been granted fast track designation by the U.S. Food and Drug Administration (FDA) in STK11-mutated advanced metastatic non-small cell lung cancer and was also reported to show selective sensitivity towards ovarian cancers (OC) with a Mesenchymal molecular subtype. In this study, we further explored AXL's role in mediating DNA damage responses by using OC as a disease model. AXL inhibition using R428 resulted in the increase of DNA damage with the concurrent upregulation of DNA damage response signalling molecules. Furthermore, AXL inhibition rendered cells more sensitive to the inhibition of ATR, a crucial mediator for replication stress. Combinatory use of AXL and ATR inhibitors showed additive effects in OC. Through SILAC co-immunoprecipitation mass spectrometry, we identified a novel binding partner of AXL, SAM68, whose loss in OC cells harboured phenotypes in DNA damage responses similar to AXL inhibition. In addition, AXL- and SAM68-deficiency or R428 treatment induced elevated levels of cholesterol and upregulated genes in the cholesterol biosynthesis pathway. There might be a protective role of cholesterol in shielding cancer cells against DNA damage induced by AXL inhibition or SMA68 deficiency. In an ovarian cancer model, AXL inhibition results in a DDR response and sensitivity to ATR inhibition, and the AXL binding partner SAM68 shows DNA damage phenotypes upon loss, similar to AXL inhibition. [ABSTRACT FROM AUTHOR]

Varroa destructor, an ectoparasite of Apis cerana (the Eastern honeybee), has attained global notoriety following the decimation caused by its host shift to Apis mellifera. Previous studies indicated that Varroa mites have geographic and host-specific mitochondrial haplotypes (mitotypes) in A. mellifera colonies, suggesting that only a few genetic strains (i.e., Korean and Japanese mitotypes) can effectively infest A. mellifera. However, growing evidence indicates that native mite populations of A. cerana can hybridize with the mites imported with A. mellifera colonies. This raises the possibility for continuous host shifts of Varroa mites and the consequential hybridizations among mites from different localities, leading to erasure of host specificity among mites of different mitotypes. We compared mitochondrial sequence data with restriction site-associated DNA sequencing (RAD-seq) to test the veracity of the patterns indicated by mitochondrial data and to clarify the genetic differentiation of Varroa mites in Vietnam and Taiwan. Our mitotype analyses replicate previous studies, indicating that only a few Varroa mite mitotype lineages parasitize A. mellifera. However, our RAD-seq data reveal little evidence of the genetic isolation as suggested by the mitotype analyses, instead indicating that hybridization is likely occurring among Varroa mites from multiple different hosts and localities. This indicates that the local mite community of A. cerana might contribute to the genetic pool of mites parasitizing A. mellifera. Our findings suggest that the Varroa mite control strategies and the risk estimation of international apicultural trade should be reassessed. [ABSTRACT FROM AUTHOR]

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Recent years have witnessed a growing development in swarm intelligence. With its distinctive advantages in settling complex issues in practice, more and more researchers have paid attention to this point. Compared with other swarm algorithms, the symbiotic organism search (SOS) algorithm, a promising meta-heuristic evolutionary one, is featured by high convergence and high-quality solutions in the overall optimization process. However, when the SOS algorithm was proposed, it was to solve real-life problems, and there are many discrete problems to be solved by us, so some scholars discretized the SOS algorithm. The discretized SOS algorithm has the shortcoming that it is very easy to fall into the local optimum, which leads to insufficient convergence, so in this paper, we propose a multi-group discrete SOS algorithm with gene transfer and path cross for elimination strategies to improve the performance of the DSOS algorithm in solving TSP. To prove the performance and efficiency of the algorithm for the TSP problem, the symmetry problem in the TSPLIB data set is employed to verify it, and this paper compares it with other algorithms to show the practicability of the method. [ABSTRACT FROM AUTHOR]

The operation of a real aircraft engine is affected by heat. After an initial comprehensive coupled vibration study of a shaft-disk-blades rotor, the authors added heat to explore heat-elastic coupled vibrations. The assumed mode and finite element methods were applied in this study. In addition, a new material, the nickel-based super alloy K409, was also considered. Two new coupling-mode types were defined. These are the blade-heat (BH) and shaft-blade-heat (SBH) modes. The qualitative variation behaviors showed that the 1a mode changed from the SB mode to the SBH mode, and the 1b modes with four repeated eigenvalues changed from the BB mode to the BH mode. However, the process is not a simple variation, but a variety of mode change phenomena occurred. The thermal variation behaviors from 0 to 1300 °C were explored quantitatively. Steel and K409 yielded similar results. Finally, the effect of the rotational speed was explored. [ABSTRACT FROM AUTHOR]

We report a rare case of dysphagia after occipitocervical fixation, and aim to emphasize the importance of occiput-C2 angle. The kyphotic change of occiput-C2 alignment after operation might lead to dysphagia due to decreased oropharyngeal cross-section area and increased basal pressure of upper esophageal sphincter. Carefully align the occiput-C2 angle during occipitocervical fixation might reduce the incidence of postoperative dysphagia. [ABSTRACT FROM AUTHOR]

Mammalian innate immune sensor STING (STimulator of INterferon Gene) was recently found to originate from bacteria. During phage infection, bacterial STING sense c-di-GMP generated by the CD-NTase (cGAS/DncV-like nucleotidyltransferase) encoded in the same operon and signal suicide commitment as a defense strategy that restricts phage propagation. However, the precise binding mode of c-di-GMP to bacterial STING and the specific recognition mechanism are still elusive. Here, we determine two complex crystal structures of bacterial STING/c-di-GMP, which provide a clear picture of how c-di-GMP is distinguished from other cyclic dinucleotides. The protein-protein interactions further reveal the driving force behind filament formation of bacterial STING. Finally, we group the bacterial STING into two classes based on the conserved motif in β-strand lid, which dictate their ligand specificity and oligomerization mechanism, and propose an evolution-based model that describes the transition from c-di-GMP-dependent signaling in bacteria to 2'3'-cGAMP-dependent signaling in eukaryotes. The bacterial Cyclic-oligonucleotide-Based Anti-phage Signaling System (CBASS) contains a CD-NTase that synthesizes cyclic di- and tri-nucleotides, and bacterial STING proteins recognize c-di-GMP generated by CD-NTase during phage infection and signal the infected bacteria to commit suicide. Here, the authors provide insights into the molecular basis for c-di-GMP recognition of bacterial STING proteins by determining two STING protein crystal structures with bound c-di-GMP from Prevotella corporis and Myroides sp. ZB35. [ABSTRACT FROM AUTHOR]

In vitro gonad culture systems have proven useful to investigate intrinsic mechanisms of sexual reproduction in animals. Here we describe development of an in vitro culture method for coral ovaries. Mesenterial tissues containing both ovaries and mesenterial filaments were microscopically isolated from the scleractinian coral, Fimbriaphyllia ancora, and culture conditions were optimized. M199 diluted 10× (10% M199, pH 8.1) and supplemented with 25 mM HEPES and the antibiotics, ampicillin, penicillin and streptomycin, supported oocyte survival and maintained the structural integrity of ovaries during short-term culture (~ 6 days). Addition of a commercial antibiotic–antimycotic solution (Anti–Anti) and fetal bovine serum adversely affected ovary maintenance and caused tissue disintegration. Characterization of cultured ovaries showed that there is no difference in cell proliferation of ovarian somatic cells between culture Days 1 and 6. Moreover, the presence of oogonia and expression of a major yolk protein, vitellogenin, were confirmed in ovaries cultured for 6 days. This system will be useful for studying effects of a wide range of substances on coral oogenesis. [ABSTRACT FROM AUTHOR]

Background: Little is known about patients' understanding of adolescent idiopathic scoliosis (AIS). This paper aims to develop and validate the Scoliosis Misconception Scale (SMS) and to explore patients' level of misconception about AIS. Methods: A total of 195 patients who were newly referred with newly diagnosed AIS were recruited to assess their levels of misconception and psychological distress before and after their first consultation with a specialist. The 17-item SMS was administered to assess patients' level of misconception about AIS and the Kessler Psychological Distress Scale (K10) was used to measure their level of distress. Results: According to the Item Response Theory, all items were within the acceptable range from -3.69 to 2.39 for difficulty parameters, which determined the difficulty of the scale, while most of the items were within the acceptable range from 0.11 to 1.54 for the discrimination parameters, which determined the rate at which the probability of endorsing a correct item changes given ability levels. Internal consistency by marginal reliability was 0.66. One-sample t test revealed that participants on average scored 6.79 (SD = 2.12) before the first clinic session and 6.45 (SD = 2.51) after the first clinic session, both significantly higher than 0 [t(75) = 27.86, p <.001; t(75) = 22.43, p <.001]. Conclusions: Despite a longstanding clinical model that functions well to treat AIS, most patients still have significant misconceptions about the condition. This highlights the necessity to assess patients' knowledge level of a medical condition and potential generalisability of misconception–distress link to the forefront across other illnesses. [ABSTRACT FROM AUTHOR]

With the rapid changes in the global business environment, enterprises face many risks for their supply chains. The development of blockchain technology (BCT), an emerging technology, could transform supply chain activities and provides an opportunity to mitigate supply chain risks (SCRs). However, there is a lack of guidance on this issue. Therefore, this study evaluates and prioritizes the impacts of BCT on reducing SCRs. By applying the analytic hierarchy process (AHP) approach, this study identifies and assesses the nineteen BCT adoption enablers for reducing SCRs in a hierarchical structure. Results show that the sourcing process is the essential enabler when enterprises consider adopting BCT for reducing risks, and the weight of the making process is ranked second. Among the sub-criteria, the top five items are clarity of supply sources, counterfeit and shoddy products, fraud in contract fulfillment, the flexibility of capacity, and sensitivity to demand change. This study's findings may guide practitioners considering the introduction of BCT to reduce SCRs and for scholars who are developing related theories. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, without effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, in βArr2-KO mice head twitch responses are low with LSD and this psychedelic is without effects on other surrogates. The 5-HT2AR antagonist MDL100907 (MDL) blocks the LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and βArr1-KOs, but not in βArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in βArr1-KOs. Collectively, these results reveal that LSD's psychedelic drug-like actions appear to require βArr2. [ABSTRACT FROM AUTHOR]

Background: Two pharmacokinetic/pharmacodynamic studies were conducted to evaluate the potential drug–drug interaction between elagolix, an oral gonadotropin-releasing hormone receptor antagonist, and an oral contraceptive (ethinylestradiol [EE] 0.035 mg and norgestimate 0.18/0.215/0.25 mg) or progestin-only contraceptive (norethindrone 0.35 mg) in healthy premenopausal women. Methods: These phase I studies used a two-period, sequential design, where period 1 included treatment with oral contraceptives, followed by period 2 with contraceptives coadministered with elagolix 150 mg once daily. Results: In study 1, pharmacokinetic exposures for EE in period 2 increased by 30% and the norgestimate metabolites decreased by approximately 15% when coadministered with elagolix. Mean hormone exposure appeared lower for follicle-stimulating hormone (FSH; 31%), luteinizing hormone (LH; 38%), and estradiol (E2; 16%). The percentage of women with consecutive progesterone (P) concentrations above 5 nmol/L was similar in both periods. Norethindrone pharmacokinetic exposures were comparable in both periods. The hormone exposure for LH and FSH was similar, and mean E2 exposure was 32% lower in period 2. The percentage of subjects with consecutive ovulatory P concentrations was also similar in both periods (study 2). Safety and tolerability profiles were unremarkable in both studies. Conclusions: Coadministration of elagolix 150 mg once daily with oral contraceptives containing EE and norgestimate, or norethindrone, resulted in small pharmacokinetic changes in the oral contraceptive components. Similar or lower FSH, LH, and E2 exposures were observed during coadministration, with ovulatory P concentrations also comparable in both periods. The pharmacodynamic profiles of the oral contraceptives were maintained when coadministered with elagolix. [ABSTRACT FROM AUTHOR]

Mesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs' high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies' inferior solubility or affinity/specificity to the target antigen. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development. Statement of significance PDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors. Arginine methylation by PRMTs is dysregulated in cancer. Here, the authors use functional genomics screens and identify PRMT1 as a vulnerability in pancreatic ductal adenocarcinoma, and further show that PRMT1 regulates RNA metabolism and coordinates expression of genes in cell cycle progression, maintaining genomic stability and tumour growth. [ABSTRACT FROM AUTHOR]

This study examines the ionosphere response to gravitational forces of the lunar phase and dynamical disturbances of the stratospheric sudden warmings (SSWs). The total electron content (TEC) of global ionosphere maps is employed to examine responses of the equatorial ionization anomaly (EIA) crests to lunar phases and twelve SSW events during 2000–2013. The most prominent feature in the ionosphere is the EIA, characterized by two enhanced TEC crests at low latitudes straddling the magnetic equator, which can be used to observe ionospheric plasma dynamics and structures. Results show that the EIA crest appearance time on new/full moons (first/third quarters) leads (lags) that of the overall 14-year average, which causes a pattern of TEC morning enhancements (suppressions) and afternoon suppressions (enhancements). A statistical analysis shows that SSWs can also significantly cause the early appearance of EIA crests, regardless of the lunar phase. Thus, both lunar phase and SSWs can significantly modulate the appearance time of EIA crest and ionospheric plasma dynamics and structures. [ABSTRACT FROM AUTHOR]

The factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = − 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < − 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27–0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48–1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation. [ABSTRACT FROM AUTHOR]

This paper develops a stochastic approach to impose regularity properties on a directional output distance function (DODF) and an output distance function, which can be estimated by maximum likelihood. We use the resulting parameter estimates to evaluate efficiency and total factor productivity (TFP) growth for Taiwan's commercial banks over the period 2002–2015 and claim that the failure of considering the regularity restrictions and the exclusion of undesirables lead to miscalculated efficiency measures and productivity gains. The outcomes from the regularity-constrained DODF reveal that almost all data-points satisfy the regularity properties, that the managerial abilities of the banks improve after the subprime crisis of 2007, and that the sample banks' TFP grow at an average rate of 1.93% per annum, whereby technical change is the driving force. However, our estimates show downward trends in the growth rate of TFP and technical change. [ABSTRACT FROM AUTHOR]

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both "normal TSAT low iron" and "low TSAT low iron" groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13–2.16 and OR 2.36; 95% CI 1.76–3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00–2.83 and OR 1.94; 95% CI 1.11–3.40, respectively). In conclusion, CKD stage 1–4 patients with normal TSAT but low serum iron are still at risk for anemia. [ABSTRACT FROM AUTHOR]

We fabricated tantalum pentoxide (Ta2O5) channel waveguides and used them to experimentally demonstrate higher-order mode supercontinuum (SC) generation. The Ta2O5 waveguide has a high nonlinear refractive index which was in an order magnitude of 10–14 cm2/W and was designed to be anomalously dispersive at the pumping wavelength. To the best of our knowledge, this is the first time a higher-order mode femtosecond pump based broadband SC has been measured from a nonlinear waveguide using the phase-matching method. This enabled us to demonstrate a SC spectrum spanning from 842 to 1462 nm (at − 30 dB), which corresponds to 0.83 octaves, when using the TM10 waveguide mode. When using the TE10 mode, the SC bandwidth is slightly reduced for the same excitation peak power. In addition, we theoretically estimated and discussed the possibility of using the broadband higher-order modes emitted from the Ta2O5 waveguide for trapping nanoparticles. Hence, we believe that demonstrated Ta2O5 waveguide are a promising broadband light source for optical applications such as frequency metrology, Raman spectroscopy, molecular spectroscopy and optical coherence tomography. [ABSTRACT FROM AUTHOR]

This work presents a novel handheld mastitis detection device for detecting mastitis in dairy cattle, as well as a cattle management information system for managing cattle health information. The management information system comprises of three major subsystems—a mastitis detection device, an information display device, and a cloud database. The mastitis detection device detects and evaluates the degree of mastitis immediately before milking operations are carried out. The information display device shows the health information of the dairy cattle obtained from a cloud database and the database manages the milk production of a dairy farm. The combination of these two devices helps the dairy farmer to verify the mastitis of cattle effectively and find its health information rapidly. [ABSTRACT FROM AUTHOR]

Amaranthus tricolor L., a vegetable Amaranthus species, is an economically important crop containing large amounts of betalains. Betalains are natural antioxidants and can be classified into betacyanins and betaxanthins, with red and yellow colors, respectively. A. tricolor cultivars with varying betalain contents, leading to striking red to green coloration, have been commercially produced. However, the molecular differences underlying betalain biosynthesis in various cultivars of A. tricolor remain largely unknown. In this study, A. tricolor cultivars with different colors were chosen for comparative transcriptome analysis. The elevated expression of AmCYP76AD1 in a red-leaf cultivar of A. tricolor was proposed to play a key role in producing red betalain pigments. The functions of AmCYP76AD1, AmDODAα1, AmDODAα2, and AmcDOPA5GT were also characterized through the heterologous engineering of betalain pigments in Nicotiana benthamiana. Moreover, high and low L-DOPA 4,5-dioxygenase activities of AmDODAα1 and AmDODAα2, respectively, were confirmed through in vitro enzymatic assays. Thus, comparative transcriptome analysis combined with functional and enzymatic studies allowed the construction of a core betalain biosynthesis pathway of A. tricolor. These results not only provide novel insights into betalain biosynthesis and evolution in A. tricolor but also provide a basal framework for examining genes related to betalain biosynthesis among different species of Amaranthaceae. [ABSTRACT FROM AUTHOR]

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin. [ABSTRACT FROM AUTHOR]

This animal study aimed to elucidate the relationship of low-dose, narrow-band UVB at 308 nm with vitamin D synthesis. C57BL/6 female mice, at 3 weeks-of-age, were randomly divided into the following six groups (n = 6 at each time point of vitamin D measurement), which were: (1) normal diet without UVB irradiation; (2) VDd diet without UVB irradiation; and (3)–(6) VDd diet with 308 nm-UVB irradiation of 12.5, 25, 50, and 100 μω/cm2, respectively. All of the groups needing UVB irradiation received an exposure of 10 min per day, five days per week, and a duration of 3–5 weeks. The mice recovering from severe VDd (plasma total 25-hydroxyvitamin D level increasing from approximately 3 to over 30 ng/mL) only occurred in groups with a UVB irradiation dosage of either 50 or 100 μω/cm2. The optimal, estimated dosage for mice to recover from severe VDd was 355 mJ/cm2 within 3 weeks. Low-dose, narrow-band UVB irradiation at 308 nm is effective in improving VDd in mice. The results obtained, in addition to the especially small side effects of the above UVB irradiation formula, could be further translated to treating VDd-related disorders. [ABSTRACT FROM AUTHOR]

The macro domain is an ADP-ribose (ADPR) binding module, which is considered to act as a sensor to recognize nicotinamide adenine dinucleotide (NAD) metabolites, including poly ADPR (PAR) and other small molecules. The recognition of macro domains with various ligands is important for a variety of biological functions involved in NAD metabolism, including DNA repair, chromatin remodeling, maintenance of genomic stability, and response to viral infection. Nevertheless, how the macro domain binds to moieties with such structural obstacles using a simple cleft remains a puzzle. We systematically investigated the Middle East respiratory syndrome-coronavirus (MERS-CoV) macro domain for its ligand selectivity and binding properties by structural and biophysical approaches. Of interest, NAD, which is considered not to interact with macro domains, was co-crystallized with the MERS-CoV macro domain. Further studies at physiological temperature revealed that NAD has similar binding ability with ADPR because of the accommodation of the thermal-tunable binding pocket. This study provides the biochemical and structural bases of the detailed ligand-binding mode of the MERS-CoV macro domain. In addition, our observation of enhanced binding affinity of the MERS-CoV macro domain to NAD at physiological temperature highlights the need for further study to reveal the biological functions. Meng-Hsuan Lin et al. investigate MERS-CoV macro domain binding selectivity with NAD and NAD metabolites under various conditions. At physiological temperature, NAD is observed to have enhanced binding affinity to the MERS-CoV macro domain, shedding light on a new possible role of the MERS-CoV macro domain in viral replication. [ABSTRACT FROM AUTHOR]

Multidisciplinary care can improve the outcomes of chronic kidney disease (CKD), however the contribution of self-care behavior and knowledge about CKD is unclear. This study enrolled 454 participants with CKD stages 1–5 not on dialysis. Structured questionnaires were used to evaluate self-care behavior and kidney disease knowledge. Rapid decline in renal function was defined as the decline in estimated filtration rate > 3 ml/min per 1.73 m2/year within 1-year prior to enrollment. The mean age of all study participants was 65.8 ± 12.1 years and 55.9% were male. The elderly had better self-care behavior while younger participants had better disease knowledge. Both high self-care and high disease knowledge scores were significantly associated with and had a synergistic effect on decreasing the risk of rapid decline in renal function. CKD patients with better self-care behavior and better kidney disease knowledge had lower risk of rapid decline in renal function. [ABSTRACT FROM AUTHOR]

Objectives: Sonoelastography has been increasingly used to investigate musculoskeletal disorders. The aim of this meta-analysis was to investigate the utility of sonoelastography in diagnosing rotator cuff tendon pathology and pertinent disorders. Methods: Searching through PubMed and Embase, we systemically reviewed clinical studies in which sonoelastography has been used for imaging rotator cuff tendon pathology and relevant disorders. The primary outcome was the standardized mean difference (SMD) of tendon elasticity between shoulders (or patients) with and without the designated pathological conditions. Results: A total of 11 cross-sectional studies were included in the meta-analysis. The supraspinatus and infraspinatus tendons assessed by shear wave sonoelastography were likely to be stiffer in shoulders with adhesive capsulitis, with a SMD of 2.103 (95% confidence interval (CI), − 0.151 to 4.357, p = 0.067) and a SMD of 1.548 (95% CI, − 0.032 to 3.127, p = 0.055), respectively. Regarding rotator cuff tendinopathy, there was no significant difference in the elasticity of supraspinatus tendons evaluated by shear wave velocity (SMD = − 0.107; 95% CI, − 0.524 to 0.310, p = 0.615) or strain ratios (SMD = 0.153, 95% CI, − 2.134 to 2.440, p = 0.896). Only one study used shear wave sonoelastography to investigate patients with rotator cuff tendon tears and found tendon that elasticity was similar between diseased and normal shoulders. Conclusion: This meta-analysis revealed that supraspinatus and infraspinatus tendons tended to be stiffer in shoulders with adhesive capsulitis. Furthermore, no significant difference in tendon elasticity could be identified between shoulders with and without rotator cuff tendinopathy or tendon tears. Key Points: • Supraspinatus and infraspinatus tendons are likely to have decreased elasticity in shoulders with adhesive capsulitis, as assessed by shear wave sonoelastography. • There was no significant difference in tendon elasticity between shoulders with and without rotator cuff tendinopathy or tendon tears when evaluated by strain and shear wave sonoelastography. [ABSTRACT FROM AUTHOR]

The pathophysiological functions of matriptase, a type 2 transmembrane serine protease, rely primarily on its enzymatic activity, which is under tight control through multiple mechanisms. Among those regulatory mechanisms, the control of zymogen activation is arguably the most important. Matriptase zymogen activation not only generates the mature active enzyme but also initiates suppressive mechanisms, such as rapid inhibition by HAI-1, and matriptase shedding. These tightly coupled events allow the potent matriptase tryptic activity to fulfill its biological functions at the same time as limiting undesired hazards. Matriptase is converted to the active enzyme via a process of autoactivation, in which the activational cleavage is thought to rely on the interactions of matriptase zymogen molecules and other as yet identified proteins. Matriptase autoactivation can occur spontaneously and is rapidly followed by the formation and then shedding of matriptase-HAI-1 complexes, resulting in the presence of relatively low levels of the complex on cells. Activation can also be induced by several non-protease factors, such as the exposure of cells to a mildly acidic buffer, which rapidly causes high-level matriptase zymogen activation in almost all cell lines tested. In the current study, the structural requirements for this acid-induced zymogen activation are compared with those required for spontaneous activation through a systematic analysis of the impact of 18 different mutations in various structural domains and motifs on matriptase zymogen activation. Our study reveals that both acid-induced matriptase activation and spontaneous activation depend on the maintenance of the structural integrity of the serine protease domain, non-catalytic domains, and posttranslational modifications. The common requirements of both modes of activation suggest that acid-induced matriptase activation may function as a physiological mechanism to induce pericellular proteolysis by accelerating matriptase autoactivation. [ABSTRACT FROM AUTHOR]

Immunoassays based on sandwich immuno-complexes of capture and detection antibodies simultaneously binding to the target analytes have been powerful technologies in molecular analyses. Recent developments in single molecule detection technologies enable the detection limit of the sandwich immunoassays approaching femtomolar (10–15 M), driving the needs of developing sensitive and specific antibodies for ever-increasingly broad applications in detecting and quantifying biomarkers. The key components underlying the sandwich immunoassays are antibody-based affinity reagents, for which the conventional sources are mono- or poly-clonal antibodies from immunized animals. The downsides of the animal-based antibodies as affinity reagents arise from the requirement of months of development timespan and limited choices of antibody candidates due to immunodominance of humoral immune responses in animals. Hence, developing animal antibodies capable of distinguishing highly related antigens could be challenging. To overcome the limitation imposed by the animal immune systems, we developed an in vitro methodology based on phage-displayed synthetic antibody libraries for diverse antibodies as affinity reagents against closely related influenza virus nucleoprotein (NP) subtypes, aiming to differentiating avian influenza virus (H5N1) from seasonal influenza viruses (H1N1 and H3N2), for which the NPs are closely related by 90–94% in terms of pairwise amino acid sequence identity. We applied the methodology to attain, within four weeks, a panel of IgGs with distinguishable specificities against a group of representative NPs with pairwise amino acid sequence identities up to more than 90%, and the antibodies derived from the antibody libraries without further affinity refinement had comparable affinity of mouse antibodies to the NPs with the detection limit less than 1 nM of viral NP from lysed virus with sandwich ELISA. The panel of IgGs were capable of rapidly distinguishing infections due to virulent avian influenza virus from infections of seasonal flu, in responding to a probable emergency scenario where avian influenza virus would be transmissible among humans overlapping with the seasonal influenza infections. The results indicate that the in vitro antibody development methodology enables developing diagnostic antibodies that would not otherwise be available from animal-based antibody technologies. [ABSTRACT FROM AUTHOR]

The zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1), encoded by Plagl1 gene, is a seven-zinc-finger containing transcription factor belonging to the imprinted genome and is expressed in diverse types of embryonic and adult human tissues. Zac1 is postulated to be a tumor suppressor by inducing cell cycle arrest and apoptosis through interacting and modulating transcriptional activity of p53 as it was named. Correspondingly, the reduction or loss of Zac1 expression is associated with the incidence and progression of several human tumors, including cervical cancer, breast cancer, ovarian cancer, pituitary tumors, and basal cell carcinoma, implying the rationality of utilizing Zac1 expression as novel a biomarker for the evaluation of cervical cancer prognosis. However, to date, it has not been elucidated whether Zac1 expression is related to the prognosis of patients in clinical cervical cancer tumor samples. To address the questions outlined above, we report here a comprehensive investigation of Zac1 expression in biopsies of clinical cervical carcinoma. By analyzing Zac1 expression in various gene expression profiling of cervical cancer databases, we show the association between high Zac1 expression and poor prognosis of cervical cancer. Functional enrichment analysis showed that high Zac1 expression was associated with epithelial-mesenchymal transition (EMT), which was further observed in clinical characteristics and metastatic carcinoma samples using immunohistochemical staining. Correspondingly, hypomethylation of CpG island on Zac1 promoter was observed in samples with high Zac1 expression in cervical carcinoma. Finally, overexpression of Zac1 in a variety of cervical cancer cell lines increase their mesenchymal biomarker expression and migration, strengthening the correlation between cervical cancers with high Zac1 expression and metastasis in clinical. In summary, this research firstly revealed that identifying Zac1 expression or the methylation status of CpG site on Zac1 promoter may provide us with novel indicators for the evaluation of cervical cancer metastasis. [ABSTRACT FROM AUTHOR]

Determining thresholds by measuring class variance is highly effective for image segmentation. Otsu's method and its derivatives are common approaches that are both simple and adaptable. In spite of these methods' excellent segmentation performance, images with particular gray distributions cause a thresholding bias that limits their usefulness. We explore the limitations of Otsu's method and apply other evaluation criteria. In particular, we determine the relative homogeneity between the object and the background and then use it as a classification criterion along with a new binary thresholding method. Our method employs a histogram-smoothing method to improve valley-point selection, establishes a uniformity measure to identify the region with the best homogeneity, and identifies an optimization function for obtaining the best values for the adjustable parameters and threshold value. We also introduce a multilevel thresholding criterion based on a binary thresholding approach. Experiments using real and ground truth test images confirm the validity of our proposed method. Our method also offers a denoising ability when configured to use neighborhood information. [ABSTRACT FROM AUTHOR]

The existence and function of neurons remain largely unexplored in scleractinian corals. To gain a better understanding of neuronal functions in coral physiology, this study focused on Glycine-Leucine-Tryptophan-amide family neuropeptides (GLWamides), which have been shown to induce muscle contraction and larval metamorphosis in other cnidarians. Molecular identification and functional characterization of GLWamides in the adult stony coral Euphyllia ancora were performed. We successfully elucidated the full-length cDNA of GLWamide preprohormone in E. ancora (named EaGLW preprohormone). The deduced amino acid sequence was predicted to contain six potential GLWamide peptides. Tissue distribution analysis demonstrated that transcripts of EaGLW preprohormone were mainly expressed in the mouth (including the pharynx) and tentacles of the polyps. Immunodetection with an anti-GLWamide monoclonal antibody revealed that GLWamide neurons were mainly distributed in the epidermis of the mouth region and tentacle, in agreement with the distribution patterns of the transcripts. Treatment of the isolated mouth and tentacles with synthetic GLWamide peptides induced the contraction of these isolated tissues. Treatment of polyps with synthetic GLWamide peptides induced the contraction of polyps. These results suggest that GLWamides are involved in polyp contraction (myoactivity) in adult scleractinians. Our data provide new information on the physiological function of neuropeptides in scleractinians. [ABSTRACT FROM AUTHOR]

Urolithiasis is a common urologic problem among adults worldwide. It is interesting that urinary stones tend to recur on the same side and the pathophysiology of unilateral stone formation is not clearly understood. Researchers found that sleep posture could alter renal perfusion, and subsequent vascular injury may lead to urolithiasis formation. The aim of this study is to retrospectively evaluate the correlations between the specific sleep postures recorded in polysomnography (PSG) and the stone laterality in unilateral urinary stone formers with obstructive sleep apnea (OSA). We retrospectively reviewed patients receiving PSG for the diagnosis of OSA in our institutes between January 1st 2002 and September 30th 2016. Those had a history of unilateral urinary stones which surgical intervention was warranted were included. Supine, prone, right decubitus, and left decubitus sleep postures were determined as patients remained specific postures for more than 50% of their sleep time. The laterality of stones with sleep posture was analyzed with Chi-square test. A student t test was used to assess factors that influenced the ipsilateral stone formation. IBM SPSS Statistics 21 software was adopted to analyze the data, and p value less than 0.05 was considered statistically significant. 117 patients were enrolled in this study, among which 105 (89.7%) were male and 12 were female. The mean age at PSG examination was 53.5 ± 11.5 years. 66 patients were diagnosed as left-side urolithiasis, and 51 patients had urinary stones at right side. 58 (49.6%) patients slept predominantly in supine posture, while 53 (45.3%) patients, in decubitus posture, and no patient, in prone posture. A total of 51 patients' stones appeared at the same side as their decubitus posture (p < 0.0001). Shorter sleep stage I ratio (24.3 ± 15.5% versus 52.4 ± 24.7%, p = 0.017), longer sleep stage II + III + IV ratio (66.2 ± 21.9% versus 30.9 ± 2.8, p = 0.049), and less sleep stage change (176.6 ± 69.6 times versus 282.5 ± 91.2 times, p = 0.041) were correlated with stone formation on the same side. Age, gender, body mass index, and other polysomnographic parameters failed to demonstrate associations between the sides of urinary calculi and sleep postures. We discovered that sleep posture is associated with unilateral urolithiasis formation. Favorable sleep quality and less sleep stage changes could consolidate the correlations. Further prospective study is warranted to evaluate the effect of sleep posture and quality on non-OSA patients as well as the preventive effect of sleep posture modification on repeated unilateral stone formers. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) explains many intracellular activities, but its role in extracellular functions has not been studied to the same extent. Here we report how LLPS mediates the extracellular function of galectin-3, the only monomeric member of the galectin family. The mechanism through which galectin-3 agglutinates (acting as a "bridge" to aggregate glycosylated molecules) is largely unknown. Our data show that its N-terminal domain (NTD) undergoes LLPS driven by interactions between its aromatic residues (two tryptophans and 10 tyrosines). Our lipopolysaccharide (LPS) micelle model shows that the NTDs form multiple weak interactions to other galectin-3 and then aggregate LPS micelles. Aggregation is reversed when interactions between the LPS and the carbohydrate recognition domains are blocked by lactose. The proposed mechanism explains many of galectin-3's functions and suggests that the aromatic residues in the NTD are interesting drug design targets. Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical experiments with NMR measurements and show that the galectin-3 NTD undergoes liquid-liquid phase separation (LLPS) and agglutinates other molecules through this process. [ABSTRACT FROM AUTHOR]

This paper uses new deductions of the equation of motion and obtains new modes of change that differ from the authors' previous research. The blade-bending, shaft-torsion and ring-bending coupled vibration influence of a single-disk rotor whose blade subsystem was coated with a ring is investigated. In the last two years, the authors adopted two methods, the assumed mode method and finite element method, and compared both parties results. This article continues that work. In this paper, the phenomena of ring joint coupling vibrations are different and interesting. The authors defined two new types, the shaft-blade-ring (SBR) and blade-ring (BR) modes. These two coupling modes can be mutually affected by the shaft, blade, and ring, and no single subsystem predominates. The new change rules of natural frequencies of rotors with two to 15 blades and those of mode shapes are discussed. The influence of the ring thickness and rotational speed are also studied in this paper. [ABSTRACT FROM AUTHOR]