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Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to understand their diversification. This study uses chromosome-level genome assemblies of two hemichordates to help infer the genomic architecture of the deuterostome common ancestor and subsequent lineage-specific rearrangement events. [ABSTRACT FROM AUTHOR]

The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM‐tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20–44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid‐occipital and left facial areas. We also examined the phosphene source by adopting a high‐density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM‐tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM‐tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper‐left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near‐eye electrodermal activity (EDA) measured under the threshold‐level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM‐tACS‐induced phosphene. [ABSTRACT FROM AUTHOR]

• Long-term exposure of peritoneal dialysate and chronic inflammation were risk factors of encapsulating peritoneal sclerosis. • The miRNA-based model could be useful to assist to determine the possibility of encapsulating peritoneal sclerosis. • 5 miRNAs were key regulators of TGF-β signal pathway in mesothelial-mesenchymal transition and immune systems. • The interaction network of miRNAs and compounds indicated these these miRNAs have the therapeutic potential targets. Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-β signaling pathway. The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis, a home-based treatment, enhances patient well-being but is less preferred in Taiwan. This study uses in-depth interviews and ranking surveys to examine the decision-making process of 25 patients (13 male, 12 female, aged 31–80) who initiated peritoneal dialysis. Findings reveal that physicians significantly influence dialysis choices, with their expertise and leadership being core factors. Patients’ participation in decision-making is categorized as “active” or “passive” based on their knowledge and acceptance of treatments. Family members also play a crucial role in decisions for patients relying on familial care. Trust in physicians’ recommendations is crucial, emphasizing the importance of a strong doctor-patient relationship and ongoing support to boost patient confidence in peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) is a well-established medical technology that employs diverse light sources like lasers or light-emitting diodes to generate diverse photochemical and photophysical reactions in cells, thereby producing beneficial clinical outcomes. In this study, we introduced an 830 nm near-infrared (NIR) laser irradiation system combined with a microscope objective to precisely and controllably investigate the impact of PBM on the migration and viability of human adipose mesenchymal stem cells (hADSCs). We observed a biphasic dose-response in hADSCs' viability and migration after PBM exposure (0–10 J/cm2), with the 5 J/cm2 group showing significantly higher cell viability and migration ability than other groups. Additionally, at the optimal dose of 5 J/cm2, we used nanoparticle tracking analysis (NTA) and found a 6.25-fold increase in the concentration of extracellular vesicles (EVs) derived from hADSCs (PBM/ADSC-EVs) compared to untreated cells (ADSC-EVs). Both PBM/ADSC-EVs and ADSC-EVs remained the same size, with an average diameter of 56 nm measured by the ExoView R200 system, which falls within the typical size range for exosomes. These findings demonstrate that PBM not only improves the viability and migration of hADSCs but also significantly increases the EV yield. • Photobiomodulation (PBM) boosts mitochondrial function in human adipose stem cells (hADSCs), improving their viability and migration. • A biphasic dose-response was observed in the viability and migration of hADSCs post-PBM exposure. • At the optimal PBM dose, there was a notable 6.25-fold increase in the concentration of extracellular vesicles derived from hADSCs. [ABSTRACT FROM AUTHOR]

Niacin is indispensable for the growth and development of aquatic animals. However, the correlations between dietary niacin supplementations and the intermediary metabolism of crustaceans are still poorly elucidated. This study explored the effects of different dietary niacin levels on the growth, feed utilization, energy sensing, and glycolipid metabolism of oriental river prawn Macrobrachium nipponense. Prawns were fed with different experimental diets containing graded niacin levels (15.75, 37.62, 56.62, 97.78, 176.32, and 339.28 mg/kg, respectively) for 8 weeks. Weight gain, protein efficiency, feed intake, and hepatopancreas niacin contents all maximized in the 176.32 mg/kg group with significance noted with the control group (P < 0.05), whereas the opposite was true for feed conversion ratio. Hepatopancreas niacin concentrations increased significantly (P < 0.05) as dietary niacin levels increased, and peaked at the 339.28 mg/kg group. Hemolymph glucose, total cholesterol, and triglyceride concentrations all maximized in the 37.62 mg/kg group, while total protein concentration reached the highest value in the 176.32 mg/kg group. The hepatopancreas mRNA expression of AMP-activated protein kinase α and sirtuin 1 peaked at the 97.78 and 56.62 mg/kg group, respectively, and then both decreased as dietary niacin levels increased furtherly (P < 0.05). Hepatopancreas transcriptions of the genes related to glucose transportation, glycolysis, glycogenesis, and lipogenesis all increased with increasing niacin levels up to 176.32 mg/kg, but decreased significantly (P < 0.05) as dietary niacin levels increased furtherly. However, the transcriptions of the genes related to gluconeogenesis and fatty acid β-oxidation all decreased significantly (P < 0.05) as dietary niacin levels increased. Collectively, the optimum dietary niacin demand of oriental river prawn is 168.01-169.08 mg/kg. In addition, appropriate doses of niacin promoted the energy-sensing capability and glycolipid metabolism of this species. [ABSTRACT FROM AUTHOR]

Hip fracture is a significant health problem and is associated with increased mortality. Patients with chronic kidney disease (CKD) are more at risk of hip fracture than the general population, but the hip fracture risk is not evident among non-dialysis CKD stage 5 patients. This study aims to assess the risk of hip fracture in patients with non-dialysis CKD stage 5 comparing to those with CKD stages 1–4. Patients with non-dialysis CKD stage 5 and CKD stages 1–4 were retrieved from Taiwan longitudinal health insurance database 2011–2014. All patients were followed to the end of 2018 for the development of hip fractures. We analyze the risk of hip fracture of propensity score-matched patients with CKD stage 5 compared to patients with CKD stages 1–4 using stepwise Cox regression and competing risks regression. We analyzed 5649 propensity score-matched non-dialysis CKD 1–4 patients and non-dialysis CKD 5 patients between 2011 and 2014. All patients were followed to the end of 2018, 229 (4.1%) of CKD 1–4 patients in 21,899 patient-year, and 290 (5.1%) of CKD 5 patients had hip fractures in 18,137 patient-year. CKD 5 patients had a higher risk of hip fracture than patients with CKD stages 1–4. The adjusted HR was 1.53 (95% CI 1.08–1.54) in the Cox regression with adjustments for age, gender, comorbidity, and history of fracture. In the competing risks regression, the subdistribution hazard ratio was 1.29 (95% CI 1.08–1.54). Female gender, age, history of fractures, and Charlson–Deyo comorbidity index were independently associated with increased hip fracture risks. Non-dialysis CKD 5 patients had a higher risk of hip fracture than patients with CKD stages 1–4. This association is independent of patients' age, female gender, history of fractures, and comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: In adolescence, the brain is still maturing, and disorders in maturation may affect the normal development of the brain. Exposure to titanium dioxide nanoparticles (TiO2 NPs) has various potential negative effects on the central nervous system. Bergamot essential oil (BEO) has been found to be effective for neuroprotection. Methods: The rats were injected intraperitoneally with TiO2 NPs (20 mg/kg) and/or BEO (200 mg/kg). The endogenous antioxidant state and inflammatory parameters were estimated using ELISA kits, and then the memory ability and anxiety‐like behavior in rats were assessed. Results: TiO2 NPs exposure during the adolescent period induced anxiety‐like behavior, cognitive impairment, neuroinflammation and oxidative damage in hippocampus, and BEO treatment could significantly ameliorate the neurotoxicities induced by TiO2 NPs exposure. Conclusion: Our results suggest that the negative effects of TiO2 NPs exposure during the adolescent period on anxiety‐like behavior and cognitive function may be related to oxidative stress and neuroinflammation induced by TiO2 NPs exposure. In addition, BEO may ameliorate the neurotoxicities induced by TiO2 NPs exposure in adolescent rats through the antioxidant and anti‐inflammatory activity of BEO. [ABSTRACT FROM AUTHOR]

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). So far, there is no biomarker-based prediction tool available for EPS. Matrix metalloproteinase-2 (MMP-2) is a protein involved in the breakdown of the extracellular matrix, and the effluent MMP-2 can be a potential biomarker of EPS. This study is aimed at developing a nomogram for EPS based on effluent MMP-2 levels. Patients and Methods. We enrolled 18 EPS patients and 90 gender-matched PD patients without EPS in this cross-sectional case-controlled study. The effluent MMP-2 levels and possible risk factors for EPS were analyzed using multivariable logistic regression, and a nomogram was developed. The nomogram was validated using 200 bootstrap resamples to reduce overfit bias. Results. The effluent MMP-2 levels in EPS patients were significantly higher than those in normal PD patients (p < 0.001 , Manny-Whitney U test). Effluent MMP-2 levels and PD duration were independently associated with EPS risks (p < 0.001 and p = 0.001) in multivariate logistic regression. A nomogram based on MMP-2 levels and PD duration was proposed. The AUC of MMP-2 was 0.824, and the AUC of the nomogram was 0.907 (p = 0.05). Conclusion. A nomogram based on effluent MMP-2 levels and PD duration may predict EPS with high accuracy. [ABSTRACT FROM AUTHOR]

Keywords: branchial cleft anomalies; fistula; suppuration; thyroid nodule; thyroiditis; ultrasonography EN branchial cleft anomalies fistula suppuration thyroid nodule thyroiditis ultrasonography 110 115 6 01/01/21 20210101 NES 210101 Key points Head and neck ultrasound can be used as a non-invasive image modality for the diagnosis of congenital pyriform sinus fistula (CPSF) in children. If an initial barium esophagogram fails to reveal the sinus tract, repeated study is suggested 4-6 weeks later, following remission of the infectious process.4 CT and MR imaging with contrast medium are helpful diagnostic modalities for cases that present with a solid neck mass or acute swelling of a cervical cyst. Hosokawa et al7 described detailed ultrasonic findings of the caudal site of the sinus tract of the lateral cervical sinus, a hypoechoic sinus tract located between the internal and external carotid arteries; the caudal site of the lateral cervical sinus extends antero-superiorly to the external carotid artery. Gan et al9 reported the ultrasonic findings of three cases of pyriform sinus fistula: two presented with an abscess involving the thyroid gland and adjacent tissue, the other presented with a hyperechoic line of the gas pocket within the fistula. [Extracted from the article]

Studies in various animals have shown that asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification in early embryos. However, comprehensive analyses of the maternal transcriptomes with spatial information are scarce and limited to a handful of model organisms. In cephalochordates (amphioxus), an early branching chordate group, maternal transcripts of germline determinants form a compact granule that is inherited by a single blastomere during cleavage stages. Further blastomere separation experiments suggest that other transcripts associated with the granule are likely responsible for organizing the posterior structure in amphioxus; however, the identities of these determinants remain unknown. In this study, we used high-throughput RNA sequencing of separated blastomeres to examine asymmetrically localized transcripts in two-cell and eight-cell stage embryos of the amphioxus Branchiostoma floridae. We identified 111 and 391 differentially enriched transcripts at the 2-cell stage and the 8-cell stage, respectively, and used in situ hybridization to validate the spatial distribution patterns for a subset of these transcripts. The identified transcripts could be categorized into two major groups: (1) vegetal tier/germ granule-enriched and (2) animal tier/anterior-enriched transcripts. Using zebrafish as a surrogate model system, we showed that overexpression of one animal tier/anterior-localized amphioxus transcript, zfp665, causes a dorsalization/anteriorization phenotype in zebrafish embryos by downregulating the expression of the ventral gene, eve1, suggesting a potential function of zfp665 in early axial patterning. Our results provide a global transcriptomic blueprint for early-stage amphioxus embryos. This dataset represents a rich platform to guide future characterization of molecular players in early amphioxus development and to elucidate conservation and divergence of developmental programs during chordate evolution. Author summary: Studies in model animals have shown that asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification in early embryos. However, comprehensive analyses of the maternal transcriptomes with spatial information are limited to a handful of organisms. Here, we use a PCR-based single-cell RNA sequencing approach on separated blastomeres from the cleavage stage embryos of amphioxus, an early-branching chordate. We generate a spatial transcriptomic map and demonstrate the mosaic property of the early amphioxus embryo, contrasting to the general notion that its embryogenesis is highly regulative. Our cross-species experiments further provide evidence to support that some of the identified factors play functions in early axial patterning. Our results provide a global transcriptomic blueprint that can serve as a rich platform for guiding future characterization of molecular players in early amphioxus development and for comparative studies on testing conservation and divergence of developmental programs during chordate evolution. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory disease of intestinal tract, and Periplaneta americana has been found to be effective in the treatment for UC. The purpose of the study was to investigate the therapeutic effect of Periplaneta americana extract Ento-A on UC in rats induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and to explore its mechanism. The Sprague-Dawley (SD) rats were randomly divided into normal control group; TNBS-treated group; sulfasalazine (SASP) treated group; Ento-A low- (50 mg/kg), medium- (100 mg/kg), and high-dose (200 mg/kg) groups, respectively. The UC model of rats was induced via TNBS. Disease activity index (DAI) was used to evaluate the severity of UC in rats. The macroscopic and microscopic damages of colon were accessed by colon mucosa damage index (CMDI) and histopathological score (HS), respectively. The levels of interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of myeloperoxidase (MPO), transforming growth factor-β1 (TGF-β1), and epidermal growth factor (EGF) in colonic mucosa were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the normal control group, the TNBS-treated group showed increase in DAI, CMDI, HS, IL-17, TNF-α, IFN-γ as well as MPO and decrease in the levels of IL-4, EGF, and TGF-β1. However, Ento-A-administrated groups reversed the changes in the DAI, CMDI, HS, and the cytokines caused by TNBS. The study indicates that Periplaneta americana extract Ento-A can effectively alleviate the inflammation in TNBS-induced UC of rats, and the mechanism of that may be related to restoring the balance of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cytokines. [ABSTRACT FROM AUTHOR]

The exploitation of high-quality borophosphate-based phosphor products is currently garnering a significant research focus in solid-state light source. The interest is due to its low-cost and environment-friendly synthesis. In this paper, a new La 7 O 6 (BO 3)(PO 4) 2 (LBP):Dy phosphor was developed via sintering at 1673 K for 3 h under an air atmosphere. Structural characterization indicates that all of the prepared products are the monoclinic phases with the space group P 2 1 /n. A comparison of the surface chemical states of the elemental compositions for the LBP host versus optimal LBP:13%Dy product was conducted via X-ray photoelectron spectroscopy. Optical characterization shows that the Dy-doped products exhibited visible light emissions of Dy3+ from 4F 9/2 to 6H 15/2 , 6H 13/2 , and 6H 11/2 upon exposure to 348 nm near-ultra violet irradiation. The dominant emission (yellow, 576 nm) belongs to the 4F 9/2 → 6H 13/2 transition. The best Dy content for doping was 13 mol%, and content quenching occurred due to dipole – dipole interaction. The measured decay lifetime and calculated chromatic properties together manifest that the optimal LBP:13%Dy phosphor shows potential as a yellow ingredient in solid-state lighting. [ABSTRACT FROM AUTHOR]

Rationale: Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis and pancreatic cancer (PC) is one of the most lethal types of cancer that is symptomless in the early stage. Because the clinical and image findings of CP can overlap that of pancreatic cancer (PC) which leads to confusion in the diagnosis and treatment of PC, discovery/verification/validation of more accurate protein biomarkers to diagnose CP and PC is in urgent need. Methods: The PubMed, Web of Science, and Google Scholar were searched using the keywords: 'biomarker', 'marker', 'chronic pancreatitis', "pancreatic cancer" or "proteomics" for highly related researches. We focused on the articles published after the year 2005 in this review. Results: We introduce the background to CP and PC and summarize the diagnosis of CP and PC, analytically validated protein biomarkers, and proteomic approaches for discovery/verification/validation. The potential use of mass spectrometry (MS) in clinical diagnosis is also discussed. Conclusions: Continuously improving sensitivity of MS can provide deeper proteome for new marker discovery and high reliability for protein marker verification, validation, and clinical diagnosis. The analytically validated protein markers could be considered as targeted protein biomarkers for developing a MS platform in the clinical validation process or clinical diagnosis of CP and PC. [ABSTRACT FROM AUTHOR]

Background: Acute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial.Methods: We use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event.Results: We compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times.Conclusion: Our study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory disease of intestinal tract, and Periplaneta americana has been found to be effective in the treatment for UC. The purpose of the study was to investigate the therapeutic effect of Periplaneta americana extract Ento-A on UC in rats induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and to explore its mechanism. The Sprague-Dawley (SD) rats were randomly divided into normal control group; TNBS-treated group; sulfasalazine (SASP) treated group; Ento-A low- (50 mg/kg), medium- (100 mg/kg), and high-dose (200 mg/kg) groups, respectively. The UC model of rats was induced via TNBS. Disease activity index (DAI) was used to evaluate the severity of UC in rats. The macroscopic and microscopic damages of colon were accessed by colon mucosa damage index (CMDI) and histopathological score (HS), respectively. The levels of interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of myeloperoxidase (MPO), transforming growth factor-β1 (TGF-β1), and epidermal growth factor (EGF) in colonic mucosa were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the normal control group, the TNBS-treated group showed increase in DAI, CMDI, HS, IL-17, TNF-α, IFN-γ as well as MPO and decrease in the levels of IL-4, EGF, and TGF-β1. However, Ento-A-administrated groups reversed the changes in the DAI, CMDI, HS, and the cytokines caused by TNBS. The study indicates that Periplaneta americana extract Ento-A can effectively alleviate the inflammation in TNBS-induced UC of rats, and the mechanism of that may be related to restoring the balance of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cytokines. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica , Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3–10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1β and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1β and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future. [Display omitted] • WV and WV-II exerted anti-inflammatory effect via regulating JAK/STAT signaling pathway. • WV and WV-II modulated redox homeostasis. • WV and WV-II promoted ferroptosis on treatment of RA. [ABSTRACT FROM AUTHOR]

Aim: Abdominal aortic calcification (AAC) score in dialysis patients was associated with coronary artery disease (CAD) in cross‐sectional study, but the use of AAC score in the CAD prediction was not clear. We aimed to use AAC score in the estimation of CAD occurrence in middle‐aged peritoneal dialysis (PD) patients. Methods: Middle‐aged (45–65 years old) PD patients were recruited and followed up until CAD occurrence, patient mortality, or PD failure. We quantified AAC score by lateral lumbar radiography, and used receiver operation curve (ROC) analysis to find the cut‐off value for CAD prediction. Results: There were 187 patients recruited for study with a mean follow‐up of 1027 ± 427 days. AAC score in patients with CAD during follow‐up period (9.7 ± 7.6, n = 41) was higher than in patients without CAD occurrence (5.5 ± 6.1, n = 146) (P < 0.001). Multivariate hazard ratio of AAC score for CAD was 1.07 (P = 0.044). ROC showed that AAC score of 5.5 had a sensitivity of 0.667 and a specificity of 0.581 in the prediction of CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5 (Log‐rank test, P = 0.003). Age (P = 0.002), diabetes (P = 0.002), hypertension (P = 0.032), longer dialysis vintage (P < 0.001) and lower serum potassium (P = 0.012) were parameters significantly associated with higher AAC score. Conclusion: AAC score can predict CAD occurrence in PD patients. Age, diabetes, hypertension, dialysis vintage and serum potassium level are factors associated with higher AAC score. Summary at a Glance: This is a prospective cohort study examining the correlation of abdominal aortic calcification score with the occurrence of coronary artery disease, patient mortality or technique failure. Patients with a score of greater than 5.5 had a higher cumulative incidence of coronary artery disease. [ABSTRACT FROM AUTHOR]

Studies on the gene regulatory networks (GRNs) of sea urchin embryos have provided a basic understanding of the molecular mechanisms controlling animal development. The causal links in GRNs have been verified experimentally through perturbation of gene functions. Microinjection of antisense morpholino oligonucleotides (MOs) into the egg is the most widely used approach for gene knockdown in sea urchin embryos. The modification of MOs into a membrane-permeable form (vivo-MOs) has allowed gene knockdown at later developmental stages. Recent advances in genome editing tools, such as zinc-finger nucleases, transcription activator-like effector-based nucleases and the clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) system, have provided methods for gene knockout in sea urchins. Here, we review the use of vivo-MOs and genome editing tools in sea urchin studies since the publication of its genome in 2006. Various applications of the CRISPR/Cas9 system and their potential in studying sea urchin development are also discussed. These new tools will provide more sophisticated experimental methods for studying sea urchin development. [ABSTRACT FROM AUTHOR]

Background: Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer's vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos. Methods: Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer's vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody. Results: Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18-22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8Δzf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer's vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. Conclusions: Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM. [ABSTRACT FROM AUTHOR]

Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db-/- mice. The results demonstrate that EPA and DHA alleviate high glucose-mediated impairment of tubular formation in EPCs through a rescue of neovasculogenic capability. The molecular mechanisms underlying the effects of EPA and DHA include the activation of the extracellular signal-regulated kinase 1/2, Akt/endothelial nitric oxide synthase (eNOS) and AMP-activated kinase (AMPK) signaling cascades as well as the phosphorylation of the downstream FOXO3a protein in EPCs. Moreover, EPA and DHA up-regulate the expression of c-kit, erythroid 2-related factor and heme oxygenase-1 proteins. Daily consumption of FO at dosages of 4% and 6% (wt/wt) significantly increased the level of bone marrow-derived and circulating EPCs, induced a recovery of blood flow and prevented ischemic injuries in a T2D db-/- mouse model. The effects of FO consumption were exerted the activation of Akt/eNOS and AMPK signaling cascades without any effect on the plasma VEGF level in vivo. [ABSTRACT FROM AUTHOR]

The behavior of grain and grain-boundary conductivity of acceptor (Sc)-doped ( Ba, Ca)( Ti, Zr) O3 ceramics sintered in moist reducing atmosphere and subsequently reoxidized in dry and moist atmosphere was investigated by means of impedance spectroscopy ( IS). In moist firing atmosphere, water vapor was found to react with oxygen vacancies, forming positively charged hydroxyl defects [ABSTRACT FROM AUTHOR]

Phenomenologically, bipolar disorder (BD) is characterized by biphasic increases and decreases in energy. As this is a state-related phenomenon, identifying regulators responsible for this phasic dysregulation has the potential to uncover key elements in the pathophysiology of BD. Given the evidence suggesting mitochondrial complex I dysfunction in BD, we aimed to identify the main regulators of complex I in BD by reviewing the literature and using the published microarray data to examine their gene expression profiles. We also validated protein expression levels of the main complex I regulators by immunohistochemistry. Upon reviewing the literature, we found PARK-7, STAT-3, SIRT-3 and IMP-2 play an important role in regulating complex I activity. Published microarray studies however revealed no significant direction of regulation of STAT-3 , SIRT-3 , and IMP-2 , but a trend towards downregulation of PARK-7 was observed in BD. Immunocontent of DJ-1 ( PARK-7 -encoded protein) were not elevated in post mortem prefrontal cortex from patients with BD. We also found a trend towards upregulation of DJ-1 expression with age. Our results suggest that DJ-1 is not significantly altered in BD subjects, however further studies are needed to examine DJ-1 expression levels in a cohort of older patients with BD. [ABSTRACT FROM AUTHOR]

Sea urchin embryos are a useful model system for investigating early developmental processes and the underlying gene regulatory networks. Most functional studies using sea urchin embryos rely on antisense morpholino oligonucleotides to knockdown gene functions. However, major concerns related to this technique include off-target effects, variations in morpholino efficiency, and potential morpholino toxicity; furthermore, such problems are difficult to discern. Recent advances in genome editing technologies have introduced the prospect of not only generating sequence-specific knockouts, but also providing genome-engineering applications. Two genome editing tools, zinc-finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs), have been utilized in sea urchin embryos, but the resulting efficiencies are far from satisfactory. The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system serves as an easy and efficient method with which to edit the genomes of several established and emerging model organisms in the field of developmental biology. Here, we apply the CRISPR/Cas9 system to the sea urchin embryo. We designed six guide RNAs (gRNAs) against the well-studied nodal gene and discovered that five of the gRNAs induced the expected phenotype in 60–80% of the injected embryos. In addition, we developed a simple method for isolating genomic DNA from individual embryos, enabling phenotype to be precisely linked to genotype, and revealed that the mutation rates were 67–100% among the sequenced clones. Of the two potential off-target sites we examined, no off-target effects were observed. The detailed procedures described herein promise to accelerate the usage of CRISPR/Cas9 system for genome editing in sea urchin embryos. [ABSTRACT FROM AUTHOR]

Self-assembled hydrogen-bonded networksof the polysaccharide pectin,a mechanically functional component of plant cell walls, have beenof recent interest as biomimetic exemplars of physical gels, and themicrorheological and strain-stiffening behaviors have been previouslyinvestigated. Despite this detailed rheological characterization ofpreformed gels, little is known about the fundamental arrangementof the polymers into cross-linking junction zones, the size of thesebonded regions, and the resultant network architecture in these hydrogen-bondedmaterials, especially in contrast to the plethora of such informationavailable for their well-known calcium-assembled counterparts. Inthis work, in concert with pertinent rheological measurements, anin-depth structural study of the hydrogen-bond-mediated gelation ofpectins is provided. Gels were realized by using glucona-delta-lactoneto decrease the pH of solutions of pectic polymers that had a (blockwise)low degree of methylesterification. Small-angle X-ray scattering andtransmission electron microscopy were utilized to access structuralinformation on length scales on the order of nanometers to hundredsof nanometers, while complementary mechanical properties were measuredpredominantly using small amplitude oscillatory shear rheology. [ABSTRACT FROM AUTHOR]

BACKGROUND The phytochemical composition of aqueous and ethanol extracts from Gynura bicolor DC., a vegetable, was determined. Human umbilical vein endothelial ( HUVE) cells were used to examine the antioxidative and anti-inflammatory potentials of these extracts at 1, 2 or 4% (v/v) against high-glucose-induced injury. RESULTS Both aqueous and ethanol extracts contained phenolic acids, flavonoids, carotenoids and anthocyanins in the ranges 1428-1569, 1934-2175, 921-1007 and 2135-2407 mg per 100 g dry weight respectively. Both extracts were rich in quercetin, lutein, malvidin and pelargonidin. Addition of these extracts at test doses decreased reactive oxygen species formation, preserved glutathione content and retained glutathione peroxide and catalase activities in high-glucose-treated HUVE cells ( P < 0.05). Treatments with these extracts at 2 and 4% lowered interleukin-6, tumor necrosis factor-alpha and prostaglandin E2 production and reduced cyclooxygenase-2 activity ( P < 0.05). CONCLUSION These findings suggest that this vegetable could be considered as a functional food and might provide antioxidative and anti-inflammatory protection. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Aim Diabetes is the leading cause of chronic kidney disease ( CKD) that requires dialysis. It is not clear if survival of patients with diabetes as primary kidney disease ( DKD) is different from the survival of patients with diabetes as comorbidity ( DCM). We investigated the survival of patients with DKD and patients with DCM in patients on maintenance haemodialysis ( HD) using propensity score matching approach. Methods All patients on maintenance HD in Taiwan Renal Registry Database from 1997 to 2005 were analyzed and were prospectively followed to 31 December 2008. Patients' survival was determined using Cox proportional-hazards regression. Results We analyzed the survival of 2632 patients with DCM and 13 160 matched patients with DKD. The first year mortality rate was 11.9% in patients with DCM and 13.9% in patients with DKD. The incidence density rate of overall mortality was 11.2 per 100 patient-years in patients with DCM and 12.9 in patients with DKD. Patients with DKD had a worse survival than patients with DCM ( P < 0.01). Compared to patients with DCM, the odds ratio (95% confidence interval [ CI]) for first year mortality was 1.27 (1.10-1.47) and the hazard ratio for overall mortality was 1.18 (1.12-1.25) in patients with DKD. Patients' age, male gender, comorbid liver cirrhosis, higher fasting blood glucose, lower haematocrit, and lower serum phosphorus were independently associated with higher mortality. Conclusions Patients with diabetes as primary kidney disease are associated with higher first year and overall mortality, compared to patients with diabetes as comorbidity in patients on maintenance haemodialysis. [ABSTRACT FROM AUTHOR]

Aim Frailty is a common syndrome in the elderly and is linked to poor outcomes. Walking performance is one of the indicators of frailty and can be associated with peripheral vascular disease ( PVD). The association between frailty and PVD is unclear. The present study investigates the association between frailty and PVD in the elderly. Methods This cross-sectional study was carried out in a geriatric population of ≥65-year-old residents of Taichung, Taiwan, in June 2009. The association between frailty and subclinical PVD was analyzed using logistic regression with adjustments for PVD risk factors. Results The community-based study consisted of 1036 individuals (539 male and 497 female subjects) with a mean age of 74.2 ± 6.6 years. Frailty was found in 143 (13.8%), and subclinical PVD was identified in 74 (7.1%) individuals using the Ankle Brachial Index < 0.9 as a cut-off. Frail individuals were associated with an increased risk for subclinical PVD with an odd ratios ( OR) of 3.168 (95% CI 1.803-5.566, P < 0.001). Individuals' diastolic blood pressure ( OR 0.975, 95% CI 0.951-0.999, P = 0.038) and high-density cholesterol ( OR 0.976, 95% CI: 0.956-0.996, P = 0.019) were independently associated with subclinical PVD. Conclusions Frailty syndrome in the elderly is associated with subclinical peripheral arterial disease indicated using the Ankle Brachial Index. The association between frailty and PVD is independent of subject's age, blood pressure and serum lipoprotein level. Geriatr Gerontol Int 2015; 15: 261-267. [ABSTRACT FROM AUTHOR]

Many studies have shown that chronic stress can cause neuronal damage and depression, but this exact mechanism still remains unknown. Neurons are vulnerable to lipid peroxidation-induced damage because the major part of neuronal cell membrane is polyunsaturated fatty acids that are substrate for reactive oxygen species. Since endogenous antioxidant defense systems normally eliminate production of reactive oxygen species, deficient antioxidant defense can cause oxidative stress-induced damage. In the present study, to understand the role of endogenous antioxidant defense in chronic stress-induced neuronal damage, we analyzed lipid peroxidation, total antioxidant capacity, and activities of catalase and glutathione peroxidase in frontal cortex, hippocampus and striatum of rats exposed to chronic unpredictable stress. We found that chronic unpredictable stress for four weeks in rats induced depressive-like behaviors such as anhedonia, despair and decreased exploration. Malondialdehyde, a lipid peroxidation product, is increased, but total antioxidant capacity, glutathione peroxidase activity and catalase activity are decreased in brain of rats exposed to chronic unpredictable stress. Our findings suggest that down regulation of endogenous antioxidant defense induces lipid peroxidation contributing a role to chronic stress and depression. [ABSTRACT FROM AUTHOR]

Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-a tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. [ABSTRACT FROM AUTHOR]

The safety of shear design method in the 'code for design of concrete structures' ( GB 50010-2010) for reinforced concrete members without web reinforcement was examined based on the analysis of the thick slab in a bridge that failed in shear. Based on the results of shear tests conducted on large beams with depths ranging from 500 mm to 1 200 mm, and test data of large beams and thick slabs from other researchers, the code expressions for shear strength of members without web reinforcement were evaluated. The influence of minimum web reinforcement and distributed longitudinal reinforcement on shear strength of large members was also discussed. It is shown that the shear strength of large members without web reinforcement exhibits significant size effect such that the code expressions into which a size effect factor has been incorporated are unable to characterize the influence of depth on shear strength of members, resulting in unsafe results when applying to deep beams (a/h0 < 2. 0) with low longitudinal reinforcement ratio and with depth greater than 1 000 mm, and to slender beams (a/h0 ⩾2. 0) with longitudinal reinforcement less than 1. 00% or with depth greater than 1 000 mm. Minimum stirrups required by code provisions are found to be effective for large members to avoid brittle shear failure, while distributed longitudinal reinforcement is less effective for member with depth over 1 000 mm without web reinforcement. [ABSTRACT FROM AUTHOR]

: Chronic kidney disease (CKD) patients are at risk for developing new-onset diabetes mellitus (NODM) even after hemodialysis (HD) and peritoneal dialysis (PD) treatment. It is not clear if the incidence for NODM is different in CKD patients receiving HD and PD. This study compared the risk of NODM in PD patients and HD patients. Methods: All HD and PD patients in Taiwan Renal Registry Database from 1997 to 2005 were included and all patients were followed to December 31, 2008. The risk of NODM was analyzed in PD patients and propensity score matched HD patients using logistic regression for early type NODM (< = 6 months after dialysis) and Cox regression for late type NODM (>6 months after dialysis). Results: A total of 2548 PD patients and 10192 HD patients who had no diabetes on the initiation of dialysis were analyzed. The incidence for NODM was 3.7 per 100 patient/year for HD and 2.4 for PD patients. HD patients are more at risk for developing early type NODM (p<0.001) with an adjusted odds ratio of 1.41 [95% confidence interval (CI) 1.12–1.78)]. HD patients are more at risk for late type NODM (p<0.001) with an adjusted hazard ratio of 2.01 (95% CI: 1.77–2.29). Patient’s age was negatively associated with risk of early type of NODM (p<0.001) but positively associated with risk of late type NODM (p<0.001). Conclusions: Chronic kidney disease patients receiving hemodialysis are more at risk for developing new-onset diabetes mellitus compared to those receiving peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF- α , IL-1 β and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. Among crude extracts from C. chinensis , ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N -[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2 E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p - N , N -dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)- α , interleukin (IL)-6 and IL-1 β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis. [Display omitted] [ABSTRACT FROM AUTHOR]

Six reinforced high-strength concrete beam-type specimens of different sizes with stubs columns in the middle were fabricated, and tested under low-cycle reversed loading to investigate the effect of depths on flexural behavior of reinforced high-strength concrete beams. The parameters of specimens varied in depths and ratios of longitudinal reinforcement on the top of cross sections, while the depth-width ratios of cross sections, shear span-to-depth ratios and ratios of longitudinal reinforcement on the bottom of cross sections and stirrups were constant. C70 concrete was used to cast the specimens and HRB 400 steel bars were used as longitudinal reinforcement. The influence of beam depths on nominal cracking moment, nominal yield moment, nominal ultimate moment, displacement ductility, plastic rotation capacity, stiffness degradation and energy dissipation capacity of high-strength concrete beams were investigated. It is shown that there is no apparent size effect observed on nominal cracking moment, nominal yield moment and nominal ultimate moment of reinforced high-strength concrete beams, and that all specimens subjected to cyclic loading clearly show similar stiffness degradation which is independent of beam depths, while the displacement ductility factors, rotational capacity as well as work index of specimens decrease with increasing of depths, showing significant size effect. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-9 (MMP-9) plays a critical role in cancer metastasis. Andrographolide (AP) is a diterpene lactone in the leaves and stem of Andrographis paniculata (Burm. f) Ness that has been reported to possess anticancer activity. In this study, we investigated the effect of AP on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and invasion in MCF-7 breast cancer cells and the possible mechanisms involved. The results showed that AP dose-dependently inhibited TPA-induced MMP-9 protein expression, enzyme activity, migration and invasion. In addition, AP significantly induced heme oxygenase-1 (HO-1) messenger RNA (mRNA) and protein expression. Transfection with HO-1 small interfering RNA knocked down the HO-1 expression and reversed the inhibition of MMP-9 expression by AP. HO-1 end products, such as carbon monoxide, free iron and bilirubin, suppressed the TPA-induced MMP-9 mRNA and protein expression, enzyme activity, migration and invasion in MCF-7 cells. Furthermore, TPA-induced extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylation and the DNA binding activity of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) were attenuated by pretreatment with AP and HO-1 end products. In conclusion, these results suggest that AP inhibits TPA-induced cell migration and invasion by reducing MMP-9 activation, which is mediated mainly by inhibition of the ERK1/2 and phosphatidylinositol 3-kinase/Akt signaling pathways and subsequent AP-1 and NF-κB transactivation. Additionally, induction of HO-1 expression is at least partially involved in the inhibition of TPA-induced MMP-9 activation and cell migration in MCF-7 cells by AP. [ABSTRACT FROM AUTHOR]

The coordinated migration of bilateral cardiomyocytes and the formation of the cardiac cone are essential for heart tube formation. We investigated gene regulatory mechanisms involved in myocardial migration, and regulation of the timing of cardiac cone formation in zebrafish embryos. Through screening of zebrafish treated with ethylnitrosourea, we isolated a mutant with a hypomorphic allele of mil (s1pr2)/edg5, called s1pr2as10 (as10). Mutant embryos with this allele expressed less mil/edg5 mRNA and exhibited cardia bifida prior to 28 hours post-fertilization. Although the bilateral hearts of the mutants gradually fused together, the resulting formation of two atria and one tightly-packed ventricle failed to support normal blood circulation. Interestingly, cardia bifida of s1pr2as10 embryos could be rescued and normal circulation could be restored by incubating the embryos at low temperature (22.5°C). Rescue was also observed in gata5 and bon cardia bifida morphants raised at 22.5°C. The use of DNA microarrays, digital gene expression analyses, loss-of-function, as well as mRNA and protein rescue experiments, revealed that low temperature mitigates cardia bifida by regulating the expression of genes encoding components of the extracellular matrix (fibronectin 1, tenascin-c, tenascin-w). Furthermore, the addition of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, significantly decreased the effect of low temperature on mitigating cardia bifida in s1pr2as10 embryos. Our study reveals that temperature coordinates the development of the heart tube and somitogenesis, and that extracellular matrix genes (fibronectin 1, tenascin-c and tenascin-w) are involved. [ABSTRACT FROM AUTHOR]

Rationale: Amphetamine has a significant potential for abuse and addiction. Among prolonged abusers, amphetamine withdrawal-induced depressive symptoms are common; however, their pathophysiological mechanism is not fully understood. Previously, we found that repeated treatment with amphetamine for 2 weeks induced oxidative stress in rat brain. Objectives: The purpose of the current study is to analyze whether abstinence from repeated amphetamine treatment in rats induces depressive-like behaviors and if oxidative damage in the brain continues during abstinence. Methods: Rats were given repeated treatment with amphetamine once daily at 1, 2, or 4 mg/kg for 14 days. From 10 to 14 days after final amphetamine treatment, behavioral changes were monitored using open field test, novel object recognition test, and forced swim test. Oxidative damage in the medial frontal cortex and hippocampus was analyzed by immunohistochemistry. Results: We found that drug abstinence after repeated amphetamine stimulation decreased locomotor activity and exploratory behavior in the open field test, increased immobility in the forced swim test, and had no significant effect on the recognition index in the novel object recognition test. We also found that amphetamine abstinence increased levels of 4-hydroxynonenal-protein adducts and 8-hydroxyguanosine in rat medial frontal cortex and in CA3 and dentate gyrus regions of the hippocampus. Conclusions: These results suggest that amphetamine abstinence displays depressive-like behaviors in rats and induces oxidative damage to lipids and RNA in rat brain. Our findings indicate that the process of oxidative stress may play a role in pathophysiological changes during drug abstinence from repeated amphetamine stimulation. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in tumor metastasis. Previous studies showed that polyunsaturated fatty acids exhibit an anti-cancer effect in various human carcinoma cells, but the effect of docosahexaenoic acid (DHA) and linoleic acid (LA) on metastasis of breast cancer cells is not fully clarified. We studied the anti-metastasis potential of DHA and LA in 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. We found that TPA (100 ng/ml) induced MMP-9 enzyme activity both dose- and time-dependently, and 200 μM DHA and LA significantly inhibited MMP-9 mRNA and protein expression, enzyme activity, cell migration, and invasion. Treatment with PD98059 (10 μM), wortmannin (10 μM), and GF109203X (0.5 μM) decreased TPA-induced MMP-9 protein expression and enzyme activity. TPA-induced activation of ERK1, Akt, and PKCδ was attenuated by DHA, whereas LA attenuated only ERK1 activation. GF109203X also suppressed ERK1 activation. EMSA showed that DHA, LA, PD98059, and wortmannin decreased TPA-induced NF-κB and AP-1 DNA-binding activity. Furthermore, DHA rather than LA dose-dependently increased HO-1 expression. HO-1 siRNA alleviated the inhibition by DHA of TPA-induced MMP-9 protein expression and enzyme activity in MCF-7 cells, and HO-1 knockdown reversed the DHA inhibition of cell migration. These results suggest that DHA and LA have both similar and divergent signaling pathways in the suppression of TPA-induced MCF-7 metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Equal-channel angular pressing (ECAP) was applied to the as-cast Mg–8wt.%Zn–5wt.%Al (ZA85) alloy to produce a fine-grained structure with fine and uniformly distributed Mg32 (Al, Zn)49 (τ-phase) particles. Experiments showed that the ZA85 alloy had an initial grain size of ∼150μm after casting and was significantly reduced to 4μm after six ECAP passes at 180°C. After annealing at 300°C for 1h, the average grain size merely increased to 7.1μm. This thermal stability of the fine-grained structure at temperatures at or below 325°C is attributed to the presence of the fine and well distributed τ-phase. It was demonstrated that ECAP processing greatly enhances ductility of the experimental alloy. By testing over a range of temperatures and strain rates, a maximum elongation to failure of 400% was obtained in the ECAP ZA85 alloy tested at 300°C (0.53 Tm ) with the initial strain rate of 1.0×10−4 s−1. The dominant deformation mechanism for the specimens tested at 300 and 350°C with the initial strain rates ranging from 1.0×10−4 s−1 to 1.0×10−3 s−1 is GBS controlled by grain boundary diffusion. At the higher testing temperature of 400°C, the deformation mechanism for the experimental alloy is dislocation creep. [Copyright &y& Elsevier]

This study presents an investigation on the influence of beam depth and longitudinal reinforcement ratio on shear strength. Seven reinforced concrete beams without web reinforcement with depth varying from 500 mm to 1200 mm were tested. Maximum shear crack width, crack spacing and inclinations of shear cracks were measured and shear mechanism of concrete was discussed. In addition, other shear test data found in the literature were used to supplement the experimental data. Based on test results, the shear design methods in the GB50010 code and the ACI 318 code were examined. It was found that the size effect factor in the GB50010 shear design equations was unable to represent the reduction of shear strength for large beams due to the size effect, and that both the GB50010 method and the ACI 318 method are dangerously unconservative when applied to large beams or to beams with low longitudinal reinforcement ratio. The CSA 2004 code method developed based on the Modified Compression Field Theory was also used to analysis the test data and satisfactory results were achieved. [ABSTRACT FROM AUTHOR]

Concrete specimens with different sizes confined by stirrups were tested under axial compression. Prisms with aspect ratio of 3:1 were used in the test. The specimens were divided into four groups and each group contained three identical specimens. The sectional dimensions of specimens of the four groups were 108 mm, 200 mm, 250 mm and 370 mm, respectively. To ensure identical confinement coefficient for specimens with different sizes, the same type of confining stirrups were adopted in all specimens and both diameters and spacing of confining stirrups were properly scaled. The influence of specimen size on axial compressive strength and its corresponding peak strain and ductility of confined concrete were investigated. Similar cracking patterns and failure modes were found in the test regardless of sizes of the specimens and steeper descending branches in load-axial strain curves were observed in specimens with larger sizes. It is found that there is not apparent size effect phenomenon with respect to axial compressive strength of confined concrete, while peak strains of confined concrete corresponding to the peak stresses decrease significantly with the increase of specimen sizes. The average peak strain of specimens of 370 mm is 49% of that of specimens of 108 mm showing a significant size effect. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis (MPS) is a hereditary disorder arising from lysosomal enzymes deficiency, with glycosaminoglycans (GAGs) storage in connective tissues and bones, which may compromise the airway. This retrospective study evaluated patients with MPS type IVA with airway obstruction detected via endoscopy and imaging modalities and the effects of surgical interventions based on symptoms. The data of 15 MPS type IVA patients (10 males, 5 females, mean age 17.8 years) were reviewed in detail. Fiberoptic bronchoscopy (FB) was used to distinguish adenotonsillar hypertrophy, prolapsed soft palate, secondary laryngomalacia, vocal cord granulation, cricoid thickness, tracheal stenosis, shape of tracheal lumen, nodular deposition, tracheal kinking, tracheomalacia with rigid tracheal wall, and bronchial collapse. Computed tomography (CT) helped to measure the deformed sternal angle, the cross-sectional area of the trachea, and its narrowest/widest ratio (NW ratio), while angiography with 3D reconstruction delineated tracheal torsion, kinking, or framework damage and external vascular compression of the trachea. The NW ratio correlated negatively with age (p < 0.01), showing that airway obstruction progressed gradually. Various types of airway surgery were performed to correct the respiratory dysfunction. MPS type IVA challenges the management of multifactorial airway obstruction. Preoperative airway evaluation with both FB and CT is strongly suggested to assess both intraluminal and extraluminal factors causing airway obstruction. [ABSTRACT FROM AUTHOR]

A new labdane derivative, chamaecyparisin A (1), was isolated from the methanol extract of the bark of Chamaecyparis obtusa var. formosana. Its structure was established by spectroscopic analyses including 1D and 2D NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY) and EI-MS, and by comparison with the data of known analogs. [ABSTRACT FROM AUTHOR]

Abstract: This study examined the microstructure and high-temperature tensile properties of the Mg–8wt.%Zn–5wt.%Al (ZA85) alloy that was subjected to equal channel angular extrusion (ECAE) with various passes at 180–250°C. The original grain size and precipitate size of the as-cast specimen were 150 and 100μm, respectively. The average grain size was reduced to 4μm by dynamic recrystallization and the precipitate size was reduced to 1μm after six ECAE passes at 180°C. However, the average grain size of the ECAE-processed specimens at 250°C increased from 14μm after two passes to 20μm after four passes owing to the grain growth effect. In tensile tests at 200°C, the ultimate tensile strength (UTS) and yield strength (YS) of the specimens processed with six ECAE passes at 180°C improved to 249MPa and 162MPa, respectively, compared with 105MPa (UTS) and 74MPa (YS) for the as-cast specimens. Furthermore, elongation increased from 5.1% to 28.5%. This significant improvement in the high-temperature tensile properties of the ZA85 alloy was attributed to the refined grains and the well-distributed fine Mg32(Al, Zn)49 (τ-phase) precipitates. [Copyright &y& Elsevier]

Reinforced high-strength concrete beams subjected to bending were tested to investigate the effect of depth on flexural behavior of beams. The geometry of specimens varied in cross sections with the depth-width ratios of the cross sections, the shear span ratios and longitudinal reinforcement ratios of specimens being constant. C70 concrete was used to cast the specimens and HRB 400 steel bars were used for the longitudinal reinforcement. The influence of beam depth on the nominal cracking moment, nominal yield moment, nominal ultimate flexural moment, ductility, and plastic rotation capacity of high-strength concrete beams was investigated. It is shown that there is no apparent size effect on nominal cracking moment, nominal yield moment and nominal ultimate moment of reinforced high-strength concrete beams. But the displacement ductility ratio and plastic rotation capacity show significant size effect. The displacement ductility factor and the rotational capacity of high-strength concrete beam decrease with the increasing of cross section. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents the results of an investigation on degradation of seismic performance of reinforced concrete (RC) columns damaged by reinforcement corrosion. A total of 13 reinforced concrete circular columns were tested under combined cyclic lateral displacement excursions and constant axial load after being subjected to accelerated corrosion tests. The controlled variables in the test were corrosion level and axial load ratio. The steel corrosion loss ratios ranged from 0% to 15.1%, and the axial load ratios varied from 0.15 to 0.9. Based on the test results, degradation models for loading capacity, stiffness, ductility and energy dissipation capacity of columns were proposed. Test results show that higher corrosion levels and higher axial loads result in less stable hysteretic loops with more severe strength and stiffness degradations and worse ductility, and that the energy dissipation of corroded specimens at the same displacement excursions is approximately the same as that of control specimens, regardless of the corrosion level, when the rebar corrosion loss ratio is less than 14%. [Copyright &y& Elsevier]

While ordered bicontinuous double diamond (OBDD) in blockcopolymershas always been considered as an unstable structure relative to orderedbicontinuous double gyroid (OBDG), here we report the existence ofa thermodynamically stable OBDD structure in a diblock copolymer composedof a stereoregular block. A slightly asymmetric syndiotactic polypropylene-block-polystyrene (sPP-b-PS) as cast fromxylene was found to display the OBDD morphology. When the OBDD-formingdiblock was heated, this structure transformed to the OBDG phase atca. 155 °C. Interestingly, OBDD was recovered upon cooling evenin the temperature range above melting point of sPP, indicating thatOBDD was a thermodynamically stable structure for sPP-b-PS melt, which was in contradiction to the conventional view. Wepropose that the larger free energy cost encountered in OBDD due tothe larger packing frustration may be compensated sufficiently bythe release of free energy due to local packing of the conformationallyordered segments of sPP blocks, which stabilizes the OBDD structureat the lower temperatures. [ABSTRACT FROM AUTHOR]

Abstract: Preventive or therapeutic effects of caffeic acid in brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice against inflammatory injury were examined. Caffeic acid at 0.5, 1 or 2% was supplied either pre-intake or post-intake for 4weeks. Brain caffeic acid content was increased by caffeic acid pre-intake at 1 and 2%, and post-intake at 2% (P <0.05). MPTP treatment enhanced the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-4 and IL-10 (P <0.05). Pre-intake of caffeic acid decreased the production of test cytokines (P <0.05); however, post-intake only at 2% reduced the level of IL-1beta, IL-6 and TNF-alpha (P <0.05). MPTP treatment up-regulated mRNA expression of inducible nitric oxide synthase (iNOS), neuronal NOS, cyclooxygenase (COX)-2, glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1, and increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) (P <0.05). Caffeic acid pre-intake at test doses and post-intake at 2% declined the expression of iNOS, COX-2 and GFAP; and lowered the production of NO and PGE2 (P <0.05). MPTP treatment suppressed mRNA expression of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and tyrosine hydroxylase (TH), and lowered dopamine level (P <0.05). Caffeic acid pre-intake retained the expression of these factors, maintained TH activity and protein production, and dopamine synthesis (P <0.05). These results suggest that caffeic acid is a potent neuroprotective agent against the development of Parkinson''s disease. [Copyright &y& Elsevier]

Summary Discoveries about antimicrobial peptides and plant defence activators have made possible the de novo and rational design of novel peptides for use in crop protection. Here we report a novel chimeric protein, Hcm1, which was made by linking the active domains of cecropin A and melittin to the hypersensitive response (HR)-elicitor Hpa1 of Xanthomonas oryzae pv. oryzicola, the causal agent of rice bacterial leaf streak. The resulting chimeric protein maintained not only the HR-inducing property of the harpin, but also the antimicrobial activity of the cecropin A-melittin hybrid. Hcm1 was purified from engineered Escherichia coli and evaluated in terms of the minimal inhibitory concentration (MIC) and the 50% effective dose (ED50) against important plant pathogenic bacteria and fungi. Importantly, the protein acted as a potential pesticide by inducing disease resistance for viral, bacterial and fungal pathogens. This designed drug can be considered as a lead compound for use in plant protection, either for the development of new broad-spectrum pesticides or for expression in transgenic plants. [ABSTRACT FROM AUTHOR]