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Background: Neuro-inflammation is regarded as one of the critical pathogenesis in neurodegenerative diseases, which is characterized by the activated microglial cells. Pectolinarin (Pec), a natural flavonoid that exists in many Chinese herbal medicines, has been reported to have various biological activities. However, the effects and mechanisms on neuro-inflammation are not clear. Methods: In this study, the inhibitory effects and mechanisms of Pec on neuro-inflammation were investigated in the LPS-stimulated microglial BV2 cells. BV2 microglial cells were treated with Pec or vehicle, followed by LPS. Enzyme-linked immunosorbent assay, real-time quantitative PCR, nitric oxide and reactive oxygen species assay, and western blot were performed to examine the effects of Pec on neuro-inflammatory responses. Results: We showed that Pec significantly inhibited the expression of tumor necrosis factor α and interleukin 6 in mRNA and protein levels induced by LPS. Moreover, the production of nitric oxide, iNOS, reactive oxygen species, and COX-2 were suppressed by Pec in LPS-stimulated microglial BV2 cells. In addition, Pec inhibited LPS-induced inflammation via nuclear factor kappa B signaling pathway, as evidenced by the reduction of the phosphorylation of inhibitor of nuclear factor kappa-B kinase, the degradation of IκBα, and the nuclear translocation of p65. Conclusion: Taken together, Pec exhibited anti-inflammatory effects in LPS-stimulated microglial BV2 cells via nuclear factor kappa B signaling pathway, which might provide therapeutic potential for neuro-inflammation and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Livestock grazing and the collection of bamboo shoots are the main threats to giant panda (Ailuropoda melanoleuca) habitat in the Liangshan Mountains in China. It is important to clarify the effect of these disturbances to the giant panda to formulate targeted management policies. Based on species distribution models and daily activity models, we investigated the effects of livestock grazing and bamboo shoot collection on giant pandas from May 2021 to July 2022. Our results indicated the giant panda's suitable habitat in the reserve covered 51.83 km² (15.02% of the reserve area). Grazing and bamboo shoot collection led to losses of 19.08 km² and 7.68 km² of suitable habitat, respectively. Together, the 2 activities resulted in a loss of 28.35 km² of suitable habitat, which was more than half of the area of panda habitat. The areas of suitable habitat for giant pandas significantly overlapped with the areas affected by both disturbances. Giant pandas did not show significant differences in daily activity rhythms under a single disturbance, but the daily activity rhythms of giant pandas differed when we compared the area combining the 2 disturbances with the undisturbed area. Our study reveals that the anthropogenic disturbances in the reserve have varying effects on the suitable habitat range and daily activity rhythm of giant pandas and evidence of a synergistic effect. Therefore, when formulating relevant conservation policies, it is important to fully evaluate the extent and characteristics of anthropogenic disturbances in shaping the population distribution and habitat preferences of the giant panda and other wildlife to enhance the efficacy of conservation management practices. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a primary cause of dementia. The complement system is closely related to AD pathology and may be a potential target for the prevention and treatment of AD. In our study, we conducted a bioinformatics analysis to analyze the role of the complement system and its related factors in AD using Gene Expression Omnibus (GEO) data. We also conducted a functional analysis. Our study verified that 23 genes were closely related to differentially expressed complement system genes in diseases after intersecting the disease-related complement system module genes and differentially expressed genes. The STRING database was used to predict the interactions between the modular gene proteins of the differential complement system. A total of 21 gene proteins and 44 interaction pairs showed close interactions. We screened key genes and created a diagnostic model. The predictive effect of the model was constructed using GSE5281 and our study indicated that the predictive effect of the model was good. Our study also showed enriched negative regulation of Notch signaling, cytokine secretion involved in the immune response pathway, and cytokine secretion involved in immune response hormone-mediated apoptotic signaling pathway. We hope that our study provides a promising target to prevent and delay the onset, diagnosis, and treatment of AD. [ABSTRACT FROM AUTHOR]

Cigarette smoking (CS) exposure-induced airway inflammatory responses drive the occurrence and development of emphysema and chronic obstructive pulmonary disease (COPD). However, its precise mechanisms have not been fully elucidated. In this study, we explore the role of Rab26 in CS exposure modulating the inflammatory response of airway epithelium and the novel mechanism of CS exposure regulation Rab26. These data showed that CS exposure and H 2 O 2 (a type of ROS) suppressed the expression of Rab26 and increased the expression of DNMT3b in vivo and in vitro. GEO data analysis found the level of Rab26 was decreased in the lung tissue of COPD patients. CSE-induced ROS promoted DNA methylation of the Rab26 promoter and inhibited its promoter activity by elevating the DNMT3b level. Antioxidants N-Acetyl- l -cysteine (NAC), 5-Aza-2′-deoxycytidine (5-AZA) (DNA methylation inhibitor) and DNMT3B siRNA alleviated CSE's inhibitory effect on Rab26 expression in vitro. Importantly, NAC alleviated the improved expression of Rab26 and reduced DNMT3B expression, in the airway of smoking exposure as well as attenuated the inflammatory response in vivo. Overexpression of Rab26 attenuated CSE-induced production of inflammatory mediators through part inactivation of p38 and JNK MAPK. On the contrary, silencing Rab26 enhanced p38 and JNK activation and aggravated inflammatory response. These findings suggest that ROS-mediated Rab26 promoter hypermethylation is a critical step in cigarette smoking-induced airway epithelial inflammatory response. Restoring Rab26 in the airway epithelium might be a potential strategy for treating airway inflammation and COPD. [Display omitted] • CSE-induced ROS promoted DNA methylation of Rab26 promoter in airway epithelium. • Rab26 suppressed the CSE-induced inflammatory response of airway epithelium by partly inactivating the MAPK signaling pathway. • Downregulation of Rab26 promoted CSE-induced inflammatory response through enhanced activation of p38 and JNK MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Here, we present a thermoelectric phase diagram for the SrTi1-xNbxO3 (0.05 ≤ x ≤ 1) solid solution system, which we derived from the characterization of epitaxial films. We observed two thermoelectric phase boundaries in the system, which originate from the step-like decrease in carrier effective mass at x ~ 0.3 and from a local minimum in carrier relaxation time at x ~ 0.5. The origins of these phase boundaries are considered to be related to isovalent/heterovalent B-site substitution: parabolic Ti 3d orbitals dominate electron conduction for compositions with x<0.3, whereas the Nb 4b orbital dominates when x>0.3. At x~0.5, a tetragonal distortion of the lattice, in which the Bsite is composed of Ti4+ and Nb4+ ions, leads to the formation of tail-like impurity bands, which maximizes the electron scattering. These results provide a foundation for further research into improving the thermoelectric performance of SrTi1-xNbxO3. [ABSTRACT FROM AUTHOR]

Background. Combined atrial fibrillation (AF) ablation and left atrial appendage closure (LAAC) has been practiced for management of both the symptoms and the high stroke risk of AF. Data of the combined procedure in selected patients with prior stroke are limited. The aim of this study is to compare the safety and efficacy of combined catheter ablation and LAAC between AF patients with and without prior stroke. Methods and Results. This retrospective study enrolled 296 patients who underwent combined procedures of AF ablation and LAAC. Patients were divided into two groups: 81 patients with prior stroke (Stroke group) and 215 patients without prior stroke (Control group). Combined procedures were successfully performed in all the patients. Patients in the Stroke group had higher CHA2DS2-VASc scores (4.9 ± 1.2 vs. 3.2 ± 1.0, P < 0.001) and higher HAS-BLED scores (3.5 ± 1.1 vs. 3.0 ± 1.0, P < 0.001) compared with those in the Control group. Procedure-related complications in the Stroke group included two pericardial effusions and two groin hematomas, which did not differ significantly fromthe Control group (4.9% vs. 4.2%, P = 0.778). After a mean follow-up of 20 months, the AF-free rate of the Stroke group was comparable with that of the Control group (64.2% vs. 68.4%, P = 0.495). The relative risk reductions in stroke and bleeding (observed rate compared to that predicted from the CHA2DS2-VASc and HAS-BLED scores) were 80% and 79%, respectively, in the Stroke group, and 62% and 62%, respectively, in the Control group. Conclusions. The combination of catheter ablation and LAAC is safe and efficient in selected AF patients with prior stroke. It was observed that patients with prior stroke may benefit more from risk reductions of stroke and bleeding following the combined procedure. [ABSTRACT FROM AUTHOR]

In order to solve the problem of low productivity, unqualified segment length and high energy consumption during the process of crushing square bale straw caused by improper operation parameters, a 9FF square bale straw crusher was developed. In this study, by taking maize straw as the test material, the feeding speed, spindle speed of the crushing device and the state of the crushing device were taken as influence factors, and standard straw length rate, productivity per net working hour (hereinafter referred to as NWH) and energy consumption per ton of product as test indicators, the influence of the factors on the indicators were studied, and tests were carried out on the process of square bale straw crushing. By adopting the single factor test on the effect of the feeding speed, the spindle speed of the crushing device and the state of the crushing device on the test indicators, the suitable range of each factor was determined, respectively. Using the orthogonal test method, range method, variance method and comprehensive balance method, the experiment analyzed the significance of the influence of the three factors on various indicators and the order of priority. The test results showed that: the feeding speed was 5 m/min, spindle speed was 3000 r/min, and the state of the crushing device was a mixing cutter hammer, which was the best parameter combination (A1B1C1) for the processing technology of the square bale forage crusher. The standard straw length rate was 93.7%, and the productivity per NWH was 2.80 t/h, with energy consumption per ton of 4.72 kW·h/t, in which the standard straw length rate and productivity per NWH reached optimal values, and the energy consumption per ton of product was slightly higher than the optimal value in the experiment. The research results can provide a reference for the optimal design of the special crusher for square bale straw. [ABSTRACT FROM AUTHOR]

Background: There has been a significant increase, to epidemic levels, of obese and overweight women of reproductive age, causing impairments to reproductive health. Time-restricted feeding (TRF) including isocaloric intake has shown to be preventive of obesity-related disorders. However, its therapeutic ability to improve the reproductive function of female remains largely unknown. Methods: Here, we investigated the ability of TRF to improve the reproductive function in wild-type and liver-specific FGF21 knockout female mice. To study fertility, a continuous and a short-term fertility test, gonadotropin releasinghormone (GnRH), and Kisspeptin test were performed. Immortalized GnRH neuron was used to examine the direct role of liver fibroblast growth factor 21 (FGF21) on GnRH secretion. Results:We found that TRF rescues femalemice from bodyweight gain and glucose intolerance, as well as ovarian follicle loss and dysfunction of estrus cyclicity induced by high-fat diet. Furthermore, the beneficial effects of the TRF regimen on the reproductive performance were also observed in mice fed both chow and high-fat diet. However, those beneficial effects of TRF on metabolism and reproduction were absent in liver-specific FGF21 knockout mice. In vitro, FGF21 directly acted on GnRH neurons to modulate GnRH secretion via extracellular regulated protein kinases (ERK1/2) pathway. Conclusions: Overall, time-restricted feeding improves the reproductive function of female mice and liver FGF21 signaling plays a key role in GnRH neuron activity in female mice. [ABSTRACT FROM AUTHOR]

In this study, the ultra‐high‐frequency (UHF) antenna for partial discharge (PD) detection is optimised to simultaneously satisfy the requirements of low return loss and high fidelity factor (FF) in the frequency band of interest by using the modified non‐dominated sorting genetic algorithm II (MNSGA‐II). Based on the labour division strategy, the MNSGA‐II adopts an adaptive crossover and mutation possibilities instead of the fixed ones, resulting in the significant improvement of convergence rate and exploration ability. One of the Pareto‐optimal solutions is presented as the authors' proposed UHF antenna, whose performance is compared with those of both the antenna optimised by genetic algorithm and the existing wideband antennas. The experimental results show that the proposed antenna with a compact size of 0.201 λL × 0.198 λL realises the reflection coefficient less than −10 dB from 490 MHz to 1.52 GHz, and its FFs in the face‐to‐face and side‐by‐side scenarios are 0.897 and 0.845, respectively. Furthermore, the simulation results reveal that the high FF of antenna greatly increases the accuracy of PD source localisation. It indicates that the MNSGA‐II provides an excellent solution to the multiobjective optimisation problems in antenna design. [ABSTRACT FROM AUTHOR]

Aim: The feasibility and safety of performing the combined procedure of catheter ablation (CA) and left atrial appendage closure (LAAC) for atrial fibrillation (AF) have been reported by observational studies without controls. The aim of this study was to compare the procedural and long-term outcomes of combined procedures with isolated CA or LAAC.Methods and Results: This study included patients who underwent combined CA and LAAC (combined group), CA alone (CA-only group), or LAAC alone (LAAC-only group). Propensity score matching was used to select controls from the CA-only and LAAC-only groups. Each group contained 76 subjects. The procedures were successfully performed in all the patients. Procedure-related complications of the combined group included one pericardial effusion and two groin haematomas, which did not differ significantly with those of the CA-only group (3.9% vs. 2.6%, P=0.650) or the LAAC-only group (3.9% vs. 2.6%, P=0.650), respectively. The AF-free rate of the combined group was comparable with that of the CA-only group after a mean of 2 years follow-up (67.1% vs. 69.7%, P=0.727). Compared with the LAAC-only group, the combined group achieved similar complete occlusion rate at implant (94.7% vs. 93.4%) and at 45 days (82.9% vs. 85.5%). At the end of follow-up, ischemic stroke and bleeding events of the combined group were low (3.9%) and were comparable with those of the CA-only group (5.3%) and the LAAC-only group (2.6%).Conclusions: The combination of AF-CA and LAAC is safe and efficacious compared with single procedures alone. [ABSTRACT FROM AUTHOR]

Adipose tissue inflammation plays an important role in the regulation of glucose and lipids metabolism. It is unknown whether Ursolic acid (UA) could regulate adipose tissue inflammation, though it can regulate inflammation in many other tissues. In this study, 3T3-L1 adipocytes, DIO mice and lean mice were treated with UA or vehicle. Gene expression of inflammatory factors, chemokines and immune markers in adipocytes and adipose tissue, cytokines in cell culture medium and serum, and inflammation regulatory pathways in adipocytes were detected. Results showed that UA increased the expression of interleukins and chemokines, but not TNFα, in both adipocytes and adipose tissue. IL6 and MCP1 levels in the cell culture medium and mouse serum were induced by UA treatment. Cd14 expression level and number of CD14+ monocytes were higher in UA treated adipose tissue than those in the control group. Glucose tolerance test was impaired by UA treatment in DIO mice. Mechanistically, UA induced the expression of Tlr4 and the phosphorylation levels of ERK and NFκB in adipocytes. In conclusion, our study indicated that short-term UA administration could induce CD14+ monocytes infiltration by increasing the production of interleukins and chemokines in mouse adipose tissue, which might further impair glucose tolerance test. [ABSTRACT FROM AUTHOR]

An aperiodic substrate integrated waveguide (SIW) wide‐angle scanning phased array with low side‐lobe levels (SLLs) is presented. The proposed C‐band array has 16 SIW‐slot elements with aperiodic distribution. The TE10 mode of each element is excited to obtain a wide beamwidth for wide‐angle scanning potential. In addition, a genetic algorithm is used to optimize the placement of the elements to reduce the scanning SLLs of the phased array, especially in wide‐angle scanning areas. The proposed approach provides superior performance of SLLs < −11.5 dB, particularly small gain fluctuation (±1.5 dB) when scanning form −68° to +68°. Compared with the same aperture uniform array, the scanning angle and the SLLs of the proposed array have been significantly improved. [ABSTRACT FROM AUTHOR]

Blood coagulation function monitoring is important for people who are receiving anticoagulation treatment and a portable device is needed by these patients for blood coagulation self-testing. In this paper, a novel smartphone based blood coagulation test platform was proposed. It was developed based on parylene-C coated quartz crystal microbalance (QCM) dissipation measuring and analysis. The parylene-C coating constructed a robust and adhesive surface for fibrin capturing. The dissipation factor was obtained by measuring the frequency response of the sensor. All measured data were sent to a smartphone via Bluetooth for dissipation calculation and blood coagulation results computation. Two major coagulation indexes, activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured on this platform compared with results by a commercial hemostasis system in a clinical laboratory. The measurement results showed that the adjusted R-square (R2) value for APTT and PT measurements were 0.985 and 0.961 respectively. The QCM dissipation method for blood coagulation measurement was reliable and effective and the platform together with the QCM dissipation method was a promising solution for point of care blood coagulation testing. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 44-year-old male patient with repeated syncope for 5 years referred to our hospital. An electrophysiological study was performed. In addition, increasing the output from the proximal CS region may alter the atrial inputs by penetrating the AV node at more than one input. This phenomenon of treatment can be explained as vagal response caused by adjacent vagus ganglion capture.

A general and efficient Pd/phosphoramidite thioether complex-catalyzed asymmetric N-allylic alkylation of hydrazones with allylic acetates has been developed for the first time. The reaction allows for the preparation of various valuable N-substituted hydrazones with generally good yields and excellent enantioselectivities. Minor structural modification of the ligand resulted in opposite enantiomers, enabling enantiodivergent synthesis of products by the same catalytic system. [ABSTRACT FROM AUTHOR]

Sucrose nonfermenting-related kinase (SNRK) is a member of the AMPK-related kinase family, and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white adipose tissue (WAT) and brown adipose tissue (BAT), but SNRK expression diminishes in adipose tissue in obesity. In this study we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival; SNRK globally deficient pups die within 24 h after birth. Heterozygous mice are characterized by inflamed WAT and less BAT. Adipocyte-specific ablation of SNRK causes inflammation in WAT, ectopic lipid deposition in liver and muscle, and impaired adaptive thermogenesis in BAT. These metabolic disorders subsequently lead to decreased energy expenditure, higher body weight, and insulin resistance. We further confirm the significant association of common variants of the SNRK gene with obesity risk in humans. Through applying a phosphoproteomic approach, we identified eukaryotic elongation factor 1δ and histone deacetylase 1/2 as potential SNRK substrates. Taking these data together, we conclude that SNRK represses WAT inflammation and is essential to maintain BAT thermogenesis, making it a novel therapeutic target for treating obesity and associated metabolic disorders. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) production has been implicated in the promotion of cellular senescence. Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exerts antioxidant effects and enhances autophagy in various cell types. Since autophagy serves an important role in regulating ROS, it was hypothesized that the antioxidant effect of celastrol is via enhanced autophagy, thus inhibiting cell senescence. Therefore, the present study used a Senescence β‑Galactosidase Staining kit, western blot analysis and cell cycle analysis to investigate whether celastrol alleviates angiotensin (Ang) II‑induced cellular senescence by upregulating autophagy in vascular smooth muscle cells (VSMCs). The results demonstrated that celastrol reduced Ang II‑induced senescence of VSMCs. Ang II‑induced generation of ROS and the subsequent VSMC senescence were counteracted by pretreatment with celastrol, determined by a ROS assay kit. Celastrol significantly upregulated VSMC autophagy, which reduced intracellular ROS and the subsequent cellular senescence induced by Ang II. Furthermore, celastrol markedly suppressed activity of the mechanistic target of rapamycin signaling pathway in VSMCs. In conclusion, the present study demonstrated that celastrol counteracts VSMC senescence probably by reducing ROS production via activation of autophagy, which may hold promise for the prevention and treatment of aging‑associated cardiovascular disorders such as atherosclerosis. [ABSTRACT FROM AUTHOR]

The present study shows the basis for the anti-inflammatory effects of pitavastatin in interleukin (IL)-1β-induced human synovial cells. The SW982 cells were pretreated with pitavastatin at different concentrations (5 μM and 10 μM), followed by IL-1β (10 ng/mL) stimulation. The results showed that pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8. Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B (Akt). It also suppressed the degradation of I kappa B alpha and blocked p65 translocation into the nucleus. These findings suggest that the mechanism underlying the inhibitory effects of pitavastatin on IL-1β-induced IL-6 and IL-8 release might be mediated by the suppression of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) signaling pathways. These results may also indicate that pitavastatin may be potentially utilized as an effective therapeutic agent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Disorders of hepatic energy metabolism, which can be regulated by endoplasmic reticulum (ER) stress, lead to metabolic diseases such as hepatic steatosis and hypoglycemia. Tunicamycin, a pharmacological ER stress inducer, is used to develop an anti-cancer drug. However, the effects of tunicamycin on hepatic energy metabolism have not been well elucidated. Mice were intraperitoneally injected with tunicamycin or vehicle. Twenty-four hours later, hepatic triglyceride and glycogen content and serum lipids profiles were analyzed, as well as the expression of lipogenic and gluconeogenic genes. Tunicamycin significantly induced hepatic a yellowish color and ER stress, as well as increasing serum levels of aspartate transaminase and alanine transaminase. Besides, tunicamycin remarkably increased hepatic triglyceride content and suppressed the expression of apolipoprotein B100. In addition, tunicamycin-treated mice had lower serum levels of triglyceride, apolipoprotein B, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Gene expression of peroxisome proliferator-activated receptor α was decreased by tunicamycin, but the protein level was increased. Furthermore, blood glucose level and hepatic glycogen content were decreased in tunicamycin-treated mice. Protein kinase B signaling was attenuated in the tunicamycin-treated liver, but the expression and activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were unchanged. Tunicamycin alters hepatic energy homeostasis by increasing triglyceride accumulation and decreasing glycogen content. [ABSTRACT FROM AUTHOR]

A compact and wideband ultra-high-frequency antenna is developed in this work. Based on the Minkowski fractal geometry of the lateral boundaries of monopole and the upper boundary of ground plane, miniaturization is realized. Meanwhile, by optimizing the dimension of the semi-elliptical part of monopole and the triangular notch of ground plane, the impedance bandwidth is enhanced. To confirm the performance of antenna, a series of experiments are conducted. The size and ratio bandwidth of antenna are compared with existing broadband ones. The proposed antenna with size of 0.3 λL × 0.25 λL covers the frequency ranging from 700 MHz to more than 3 GHz and possesses an average gain of 4.08 dBi. [ABSTRACT FROM AUTHOR]

The attainment of both high strength and toughness is the ultimate goal for most structural materials. Although ceramic material has been considered for use as a structural material due to its high strength and good chemical stability, it suffers from the limitation of low toughness. For instance, although Y2O3- stabilized tetragonal ZrO2 polycrystals (Y- TZPs) exhibit remarkable toughness among ceramics due to their phase transformation toughening mechanism, this toughness is still much weaker than that of metals. Here, we report Y- TZP- based ceramic materials with toughnesses exceeding 20 MPa m1/2, which is comparable to those of metals, while maintaining strengths over 1,200 MPa. The superior mechanical properties are realized by reducing the phase stability of tetragonal zirconia by tailoring the microstructure and chemistry of the Y- TZP. The proposed ceramic materials can further advance the design and application of ceramic- based structural materials. [ABSTRACT FROM AUTHOR]

Background/Aims: Platelet microvesicles (PMVs) contribute to angiogenesis and vasculogenesis, but the mechanisms underlying these contributions have not been fully elucidated. In the present study, we investigated whether PMVs regulate the angiogenic properties of endothelial cells (ECs) via mechanisms extending beyond the transport of angiogenic regulators from platelets. Methods: In vitro Matrigel tube formation assay and in vivo Matrigel plug assay were used to evaluate the pro-angiogenic activity of PMVs. The effects of PMVs on the migration of human umbilical vein endothelial cells (HUVECs) were detected by transwell assay and wound-healing assay. Real-time PCR and western blot were conducted to examine mRNA and protein expression of pro-angiogenic factors in HUVECs. Matrix metalloproteinase (MMP) activity was assayed by gelatin zymography. Moreover, the effects of specific MMP inhibitors were tested. Results: PMVs promoted HUVEC capillarylike network formation in a dose-dependent manner. Meanwhile, PMVs dose-dependently facilitated HUVEC migration. Levels of MMP-2 and MMP-9 expression and activity were upregulated in HUVECs stimulated with PMVs. Inhibition of MMPs decreased their pro-angiogenic and pro-migratory effects on HUVECs. Moreover, we confirmed the pro-angiogenic activity of PMVs in vivo in mice with subcutaneous implantation of Matrigel, and demonstrated that blockade of MMPs attenuated PMV-induced angiogenesis. Conclusion: The findings of our study indicate that PMVs promote angiogenesis by up-regulating MMP expression in ECs via mechanism extending beyond the direct delivery of angiogenic factors. [ABSTRACT FROM AUTHOR]

Background/Aims: Platelet microvesicles (PMVs) contribute to angiogenesis and vasculogenesis, but the mechanisms underlying these contributions have not been fully elucidated. In the present study, we investigated whether PMVs regulate the angiogenic properties of endothelial cells (ECs) via mechanisms extending beyond the transport of angiogenic regulators from platelets. Methods: In vitro Matrigel tube formation assay and in vivo Matrigel plug assay were used to evaluate the pro-angiogenic activity of PMVs. The effects of PMVs on the migration of human umbilical vein endothelial cells (HUVECs) were detected by transwell assay and wound-healing assay. Real-time PCR and western blot were conducted to examine mRNA and protein expression of pro-angiogenic factors in HUVECs. Matrix metalloproteinase (MMP) activity was assayed by gelatin zymography. Moreover, the effects of specific MMP inhibitors were tested. Results: PMVs promoted HUVEC capillary-like network formation in a dose-dependent manner. Meanwhile, PMVs dose-dependently facilitated HUVEC migration. Levels of MMP-2 and MMP-9 expression and activity were up-regulated in HUVECs stimulated with PMVs. Inhibition of MMPs decreased their pro-angiogenic and pro-migratory effects on HUVECs. Moreover, we confirmed the pro-angiogenic activity of PMVs in vivo in mice with subcutaneous implantation of Matrigel, and demonstrated that blockade of MMPs attenuated PMV-induced angiogenesis. Conclusion: The findings of our study indicate that PMVs promote angiogenesis by up-regulating MMP expression in ECs via mechanism extending beyond the direct delivery of angiogenic factors. [ABSTRACT FROM AUTHOR]

Background Distinguishing synchronous multiple primary lung cancers (SMPLCs) from intrapulmonary metastases is important. The objective of this study was to determine long-term survival in patients who underwent surgical resection for synchronous multiple lung cancers and identify additional criteria that may be useful to distinguish patients with SMPLCs from those with more advanced disease. Methods The medical records of patients with lung cancer who underwent planned resection for synchronous multiple lung cancers from 2007 to 2012 at our institutions were reviewed retrospectively. A comprehensive histologic assessment was used to determine whether the tumors were metastases or separate synchronous primary tumors. Results A total of 51 patients with synchronous multiple lung cancers underwent surgical resection. Twenty-nine patients had ipsilateral synchronous multiple lung cancers, and 22 had bilateral synchronous multiple lung cancers. No perioperative death occurred. The survival analysis of all 51 patients with synchronous multiple lung cancers who underwent planned resection of all lesions showed 3- and 5-year overall survival rates of 86% and 67%, respectively, The median overall survival was not reached. The comprehensive histologic assessment identified six patients with intrapulmonary metastasis and 45 patients with SMPLCs. Intrapulmonary metastases were associated with decreased survival. Among patients with SMPLCs, the epidermal growth factor receptor mutation distribution shown high concordant frequency rate of 35% (5/14). Conclusions Survival after surgical resection of synchronous multiple lung cancers in different lobes was promising. A comprehensive histologic assessment was useful for differentiating SMPLCs from intrapulmonary metastases. [ABSTRACT FROM AUTHOR]

A Cu(OAc)2-catalyzed domino tricyclization between naphthalene-1,8-diamine and 2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties. [ABSTRACT FROM AUTHOR]

Al-PTFE (Al-polytetrafluoroethene) is an important kind of Reactive Material (RM), however only limited importance was placed to the effect of crystallinity of PTFE on the mechanical and reactive behavior. This paper investigated the influence of crystallinity on the compression behavior of Al-PTFE at strain rates range from 10−2 to 3 × 103 s−1. Two kinds of samples were prepared by different sintering procedures to acquire different crystallinity. The samples’ crystallinity was characterized by the density method and X-ray diffraction method. The samples were tested using an electro-hydraulic press for quasi-static loading, and split Hopkinson pressure bars (SHPBs) for high strain rates. Low crystalline samples have consistently higher strength and toughness than the high crystalline samples. The phenomenon was explained by an “elastic-plastic network” model combined with the effect of chain entanglement density. A bilinear dependence of true stress on log ε was observed, and Johnson-Cook models were fitted separately according to the different strain rate sensitivity. Finally, a close connection between fracture and initiation of Al-PTFE was confirmed in quasi-static tests, SHPB tests, and drop weight tests. It was hypothesized that the high temperature at the crack tips of PTFE is an important promoting factor of initiation. [ABSTRACT FROM AUTHOR]

The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ~25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/ sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1-10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonicspiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain. [ABSTRACT FROM AUTHOR]

A compact antenna using a novel finger-connected interdigital capacitor (FC-IDC)-based composite right/left-handed transmission-line (CRLH-TL) unit cell is presented. First, the characteristics of the proposed CRLH-TL are investigated. Compared with the conventional IDC-based CRLH-TL unit cell, the proposed one has a lower -1\textst-order resonant mode. Then, an antenna using the proposed CRLH-TL unit cell is designed, fabricated, and measured. By using the conventional IDC-based CRLH-TL unit cell and the microstrip patch, another two antennas are also designed, fabricated, and measured for comparison. The measured results show that the antenna using a CRLH-TL unit cell based on FC-IDC achieves 21.98% and 32.81% reductions in operating frequencies compared with the two antennas with the same size. Additionally, the newly designed antenna can also be implemented easily with printed circuit board technology, which makes it very useful in small communication systems. [ABSTRACT FROM PUBLISHER]

Background: Highly cross-linked polyethylene (HXLPE) has been reported as an effective material for decreasing polyethylene wear and osteolysis in total knee arthroplasty (TKA). Because no single study to date has been large enough to definitively determine the benefit of HXLPE in TKA, we conducted a meta-analysis to pool the results from randomized controlled trials (RCTs) and non-RCTs to make such a determination. Methods: Potential candidate articles were identified by searching the Cochrane Library, Medline (1966-2015.10), PubMed (1966-2015.10), Embase (1980-2015.10), ScienceDirect (1985-2015.10), and other databases. "Gray studies" were identified from the included articles' reference lists. Pooled data were analyzed using RevMan 5.1. Results: Three RCTs and three non-RCTs were included in the meta-analysis. There were no significant differences between the groups in the total number of reoperations (P = 0.11), reoperations for prosthesis loosening (P = 0.08), radiolucent line (P = 0.20), osteolysis (P = 0.38), prosthesis loosening (P=0.10), and mechanical failures related to the tibial polyethylene (P= 1.00). Similarly, no significant differences between the two groups were found in postoperative total knee score (P = 0.18) or functional score (P = 0.23). Conclusions: The meta-analysis showed that compared with conventional polyethylene, HXLPE did not improve the clinical and radiographic outcomes in mid-term follow-up after TKA. Additional high-quality multicenter prospective RCTs with good design, large study populations and long-term follow-up will be necessary to further clarify the effect of HXLPE in TKA. [ABSTRACT FROM AUTHOR]

Isolectin B4-binding (IB4+) dorsal root ganglion (DRG) neurons are distinct from peptidergic DRG neurons in their terminal location in the spinal cord and respective contributions to various classes and modalities of nociception. In DRG neurons innervating the mouse colon (c-DRG neurons), the reported proportion of IB4+ population is inconsistent across studies, and little is known regarding their role in colorectal mechanonociception. To address these issues, in C57BL/6J mice, we quantified IB4+ binding after labeling c-DRG neurons with Fast Blue and examined functional consequences of ablating these neurons by IB4-conjugated saporin. Sixty-one percent of Fast Blue-labeled neurons in the L6 DRG were IB4+, and 95% of these IB4+ c-DRG neurons were peptidergic. Intrathecal administration of IB4-conjugated saporin reduced the proportion of IB4+ c-DRG neurons to 37%, which was due to the loss of c-DRG neurons showing strong to medium IB4+ intensity; c-DRG neurons with weak IB4+ intensity were spared. However, this loss altered neither nociceptive behaviors to colorectal distension nor the relative proportions of stretch-sensitive colorectal afferent classes characterized by single-fiber recordings. These findings demonstrate that more than 1 half of viscerosensory L6 c-DRG neurons in C57BL/6J mouse are IB4+ and suggest, in contrast to the reported roles of IB4+/nonpeptidergic neurons in cutaneous mechanonociception, c-DRG neurons with strong-to-medium IB4+ intensity do not play a significant role in colorectal mechanonociception. [ABSTRACT FROM AUTHOR]

The same three-component reaction of aromatic aldehyde, 1H-indazol-6-amine and 3-phenylisoxazol-5(4H)-one in refluxing ethanol under catalyst-free conditions gave two entirely different kinds of products depending on the substituents on the benzene ring. The reaction selectively gave 5H-spiro[isoxazole-4,8'-pyrazolo[3,4-f]quinolin]-5-ones with strong electron-withdrawing groups on the aromatic aldehyde, while it resulted in ring-opened pyrazoloquinoline derivatives with other substituents. The former structure was confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Recent experimental results showed that the Tg of cured resin scarcely decreased and the impact strength of resins increased by over 50% when a tetrafunctional epoxy named N,N,N',N'-tetraglycidyl-4,4'-diaminodiphenyl ether (TGDDE) was introduced to an appropriate flexible chain from a dimer fatty acid (DFA). In order to understand the reason for this phenomenon, the modification and the chemical structure of the prepolymer together with the curing reaction and the viscoelasticity of the cured resins were studied in detail in the present work. The results indicated that the modification would help the prepolymer improve its molecular mobility. As a result, the resins could be further cured, resulting in the cross-linking density increasing. This is because the curing efficiency was increased, but the tetrafunctional epoxy was not cured completely due to its large steric hindrance. Moreover, the flexibility of some parts of the networks was improved, which was beneficial for the toughness of the cured resins. Therefore, the toughness of the tetrafunctional resin was improved with little influence on the thermal properties when the epoxies were modified with an appropriate content of DFA. [ABSTRACT FROM AUTHOR]

Stretch-sensitive afferents comprise ~33% of the pelvic nerve innervation of mouse colorectum, which are activated by colorectal distension and encode visceral nociception. Stretch-sensitive colorectal afferent endings respond tonically to stepped or ramped colorectal stretch, whereas dissociated colorectal dorsal root ganglion neurons generally fail to spike repetitively upon stepped current stimulation. The present study investigated this difference in the neural encoding characteristics between the soma and afferent ending using pharmacological approaches in an in vitro mouse colon-nerve preparation and complementary computational simulations. Immunohistological staining and Western blots revealed the presence of voltage-gated sodium channel (NaV) 1.6 and NaV1.7 at sensory neuronal endings in mouse colorectal tissue. Responses of stretch-sensitive colorectal afferent endings were significantly reduced by targeting NaV1.6 using selective antagonists (μ-conotoxin GIIIa and μ-conotoxin PIIIa) or tetrodotoxin. In contrast, neither selective NaV1.8 (A803467) nor NaV1.7 (ProTX-II) antagonists attenuated afferent responses to stretch. Computational simulation of a colorectal afferent ending that incorporated independent Markov models for NaV1.6 and NaV1.7, respectively, recapitulated the experimental findings, suggesting a necessary role for NaV1.6 in encoding tonic spiking by stretch-sensitive afferents. In addition, computational simulation of a dorsal root ganglion soma showed that, by adding a NaV1.6 conductance, a single-spiking neuron was converted into a tonic spiking one. These results suggest a mechanism/channel to explain the difference in neural encoding characteristics between afferent somata and sensory endings, likely caused by differential expression of ion channels (e.g., NaV1.6) at different parts of the neuron. [ABSTRACT FROM AUTHOR]

Measuring the excitability of individual axons is complicated by the prohibitive difficulty in obtaining intracellular recordings. Here, we present an innovative methodology that enables local excitability to be measured anywhere in a channelrhodopsin (ChR2)-expressing neuron. The approach hinges on activating ChR2 in a spatially and temporally precise manner while recording the resulting spike train from a remote site. We validated this approach in primary afferent neurons (PANs). Initial encoding of somatosensory stimuli relies on transduction of the physical stimulus into a receptor potential and transformation of the receptor potential into a spike train; the transformation process depends on the excitability of the most distal PAN endings but, as explained above, is extraordinarily difficult to study in situ using traditional methods. Using ChR2-based photoactivation, we show 1) that excitability differs between the distal endings and more proximal portions of PAN axons, 2) that the transformation process differs between PANs, and 3) that the transformation process is directly affected by inflammation. Beyond presenting an innovative method by which to study axonal excitability, this study has validated its utility in helping to decipher the earliest stages of somatosensory encoding. [ABSTRACT FROM AUTHOR]

The Cu/ZSM-5, Ce/ZSM-5 and Cu-Ce/ZSM-5 catalysts were prepared and characterized in this investigation and the catalytic activity of carbon monoxide (CO) combustion under these catalysts was determined by temperature-programmed oxidation. The activity for the CO combustion follows the decreasing order: Cu-Ce/ZSM-5 > Cu/ZSM-5 > Ce/ZSM-5, indicated by lower ignition, light-off, extinction temperature and broader hysteresis determined via both heating and cooling feeding process. The CO adsorbed on the copper sites to form Cu + –CO complexes, monodentate and bidentate carbonates was considered to be the crucial step for CO catalytic combustion. At the CO concentration ≥5 vol.%, the CO self-sustained combustion was achieved over the Cu-Ce/ZSM-5 catalyst. One reason is due to formation of Cu 2+ ions incorporated into cerium oxides, which are more reducible than the copper clusters, minicrystals and bulk CuO particles. Another reason is attributable to the formation of Ce 4+ /Ce 3+ redox couple, which facilitates oxygen transport on the catalyst surface. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase phosphatase 3 (MKP-3) is a negative regulator of extracellular signal-related kinase signaling. Our laboratory recently demonstrated that MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. This study shows that MKP-3 deficiency attenuates body weight gain induced by a high-fat diet (HFD) and protects mice from developing obesity-related hepatosteatosis. Triglyceride (TG) contents are dramatically decreased in the liver of MKP-3-/- mice fed an HFD compared with wild-type (WT) controls. The absence of MKP-3 also reduces adiposity, possibly by repressing adipocyte differentiation. In addition, MKP-3-/- mice display increased energy expenditure, enhanced peripheral glucose disposal, and improved systemic insulin sensitivity. We performed global phosphoproteomic studies to search for downstream mediators of MKP-3 action in liver lipid metabolism. Our results revealed that MKP-3 deficiency increases the phosphorylation of histone deacetylase (HDAC) 1 on serine 393 by 3.3-fold and HDAC2 on serine 394 by 2.33-fold. Activities of HDAC1 and 2 are increased in the livers of MKP-3-/- mice fed an HFD. Reduction of HDAC1/2 activities is sufficient to restore TG content of MKP-3-/- primary hepatocytes to a level similar to that in WT cells. [ABSTRACT FROM AUTHOR]

The Pd/sulfoxide--phosphine-catalyzed highly enantioselective allylic etherification and amination with a wide range of O- and N-nucleophiles have been developed (up to 97% yield, 98.5% ee). The products can also be conveniently transformed into biologically active chiral heterocycles. [ABSTRACT FROM AUTHOR]

Long-term treatment with glucocorticoids (GCs) or dysregulation of endogenous GC levels induces a series of metabolic diseases, such as insulin resistance, obesity and type 2 diabetes. We previously showed that MAP kinase phosphatase-3 (MKP-3) plays an important role in glucose metabolism. The aim of this study is to investigate the role of MKP-3 in GC-induced metabolic disorders. Dexamethasone (Dex), a synthetic GC, increases MKP-3 protein expression both in cultured hepatoma cells and in the liver of lean mice. This effect is likely mediated by forkhead box protein O1 (FOXO1) because disruption of endogenous FOXO1 function by either interfering RNA mediated FOXO1 knockdown or overexpression of a dominant negative FOXO1 mutant blocks Dex-induced upregulation of MKP-3 protein. In addition, overexpression of FOXO1 is sufficient to induce MKP-3 protein expression. MKP-3 deficient mice are protected from several side effects of chronic Dex exposure, such as body weight gain, adipose tissue enlargement, hepatic lipid accumulation, and insulin resistance. The beneficial phenotypes in mice lacking MKP-3 are largely attributed to the absence of MKP-3 in the liver since only hepatic insulin signaling has been preserved among the three insulin target tissues (liver, muscle and adipose tissue). [ABSTRACT FROM AUTHOR]

Highlights: [•] We propose an integrated facility location and product distribution–collection model for bidirectional flows. [•] We develop an efficient Lagrangian relaxation-based heuristic to address the proposed model. [•] We apply the heuristic in an industrial case study. [•] Several interesting managerial insights are reported from numerous computational experiments. [Copyright &y& Elsevier]

Highlights: [•] Zirconia introduction favors copper dispersion and inhibits copper crystallization. [•] Zirconia addition is beneficial to enriching copper species on the ZSM-5 surface. [•] The interaction between copper and zirconium enhances the lattice oxygen and site reducibility. [•] The Cu-Zr/ZSM-5 presents a wide activity window within the range of diesel exhaust temperatures. [ABSTRACT FROM AUTHOR]

MYH9 encodes the heavy chain of nonmuscle myosin IIA, a ubiquitously expressed cytoplasmic myosin that regulates the actin cytoskeleton, cell migration, cell polarization, and signal transduction in cancer cells. Here, we investigated the role of MYH9 in cancer stem cells (CSCs) associated with esophageal cancer (EC). The subcellular localization of MYH9 was investigated in SKGT‐4 cells through immunofluorescent analysis. MYH9+ and MYH9− spheroid cells were derived from SKGT‐4 cells by flow cytometry and compared for self‐renewal capacity, tumorigenicity, CD133 positivity, cisplatin resistance, and phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) activity. MYH9 messenger RNA expression was assessed in 30 EC patients by quantitative reverse transcription‐polymerase chain reaction. Kaplan–Meier curves were plotted to explore the influence of MYH9 on EC survival. MYH9 localized to the plasma membrane, cytoplasm, and nucleus of SKGT‐4 cells. Spheroid cells displayed higher MYH9 expression and positivity compared to parental SKGT‐4 cells. MYH9+ cells showed strong CSC characteristics, including in vivo tumorigenicity, migration, invasion, cisplatin resistance, and CD133+ positivity. MYH9 activated the PI3K/AKT/mTOR axis in CSCs and was upregulated in EC patients with poor survival. Collectively, these data show that MYH9 significantly promotes tumorigenesis by regulating PI3K/AKT/mTOR signaling in EC. MYH9 expression remarkably correlates with poor prognosis and represents a novel biomarker and drug target for the diagnosis and treatment of EC. [ABSTRACT FROM AUTHOR]

Background: Severe burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed.Methods: A multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment.Results: In total, 55 adult burn patients with a total burn surface area (TBSA) of 30-70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), β2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05).Conclusions: Glutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible. [ABSTRACT FROM AUTHOR]

We achieve enhanced actuation of the 2nd-order resonance of a microcantilever in a capacitive microcantilever structure featured by a dual coplanar counter electrodes configuration. A torque about the static point of the 2nd eigenmode is generated in this configuration and therefore enables effective actuation of the 2nd-order resonance. It is further confirmed that the torque has the effect of suppressing the 1st-order resonance. As a result, the frequency response curve of the microcantilever beam can be modulated. Our results suggest that electric actuation of any higher-order resonances of the microcantilever can be realized through a rational design of counter electrodes. [ABSTRACT FROM AUTHOR]

Abstract: Discharge characteristics and abatement of volatile organic compounds using plasma reactor packed with ceramic Raschig rings were investigated. It was found that the gap equivalent capacitance decreased with increasing voltage while the dielectric barrier equivalent capacitance increased initially and stabilized at about 700 pF. Compared with empty reactor, toluene removal was significantly enhanced by ceramic Raschig rings, 97% against 48%. With respect to the energy yield in the presence of padding, the efficiency was remarkably improved up to 10 g/kWh, which was 2 times higher than that of 5 g/kWh in the absence of padding with removal ratio exceeding 50%. [Copyright &y& Elsevier]

In vivo methylation and demethylation processes were simultaneously investigated in freshwater tilapia after dietary exposure to mercury (198Hg(II) and methyl200Hg). During one month dietary exposure followed by two month depuration, both MeHg and THg increased continuously in muscle tissues but decreased in liver during depuration, indicating the inter-organ transportation of MeHg from liver toward muscle. Direct evidence of in vivo net methylation process in freshwater tilapia was observed. Specifically, 0.67-1.60% of the ingested Hg198(II) was converted into Me198Hg and deposited in fish muscle at the end of depuration. The methylation potential in terms of methylated fraction was elevated at higher temperature and decreased at higher dosage. However, no direct evidence of MeHg demethylation was observed. In contrast to some previous reports of dose-dependent demethylation, the percentage of MeHg in the liver decreased significantly with increasing THg concentrations, likely due to the faster inter-organ MeHg transportation from liver toward muscle. Our study demonstrates the important role of organ- and species-specific biodynamics in understanding mercury transformation and speciation in fish. The observed in vivo methylation process in tilapia was slow, suggesting that the high %MeHg in fish should be mainly derived from MeHg ingestion instead of in vivo transformation. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is characterized by altered bowel habits, persistent pain and discomfort, and typically colorectal hyper-sensitivity. Linadotide, a peripherally restricted 14 aa peptide approved for the treatment of IBS with constipation, relieves constipation and reduces IBS-associated pain in these patients presumably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic guanosine monophosphate (cGMP) from intestinal epithelial cells. We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primary downstream effector of that activation, cGMP, directly modulates responses and sensi-tization of mechanosensitive colorectal primary afferents. The distal 2 cm of mouse colorectum with attached pelvic nerve was harvested and pinned flat mucosal side up for in vitro single-fiber recordings, and the encoding properties of mechanosensitive afferents (serosal, mucosal, muscular, and muscular-mucosal; M/M) to probing and circumferential stretch studied. Both cGMP (10-300 /AM) and urogua-nylin (1-1000 nM) applied directly to colorectal receptive endings significantly reduced responses of muscular and M/M afferents to stretch; serosal and mucosal afferents were not affected. Sensitized responses (i.e., increased responses to stretch) of muscular and M/M afferents were reversed by cGMP, returning responses to stretch to control. Blocking the transport of cGMP from colorectal epithelia by probenecid, a mechanism validated by studies in cultured intestinal T84 cells, abolished the inhibitory effect of uroguanylin on M/M afferents. These results suggest that GC-C agonists like linaclotide alleviate colorectal pain and hypersensitivity by dampening stretch-sensitive afferent mechanosensitivity and normalizing afferent sensitization. [ABSTRACT FROM AUTHOR]