Search

An increasing variety of organic reactions have been developed for the synthesis of more structurally stable and multifunctional COFs. Here, we report a class of β-ketamine linked covalent organic frameworks that were constructed through the CeCl 3 -catalyzed multi-component Mannich reaction at room temperature. And the TAD-COF obtained based on this method could significantly promote the light-driven oxidative hydroxylation of arylboronic acids., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Demand for accurate estimation of coastal blue carbon sequestration rates in a regular interval has recently surged due to the increasing awareness of nature-based climate solutions to alleviate adverse impacts stemming from the recent global warming. The robust estimation method is, however, far from well-established. The international community requires, moreover, to quantify its effect of "management." This article tries to provide the environmental isotope community with basic biophysical features of coastal blue carbon ecosystems to identify a suitable set of environmental isotopes for promoting coastal ocean-based climate solutions. This article reviews (i) the primary biophysical characteristics of coastal blue carbon ecosystems and hydrology, (ii) their consequential impact on the accumulation and preservation of organic carbon (OC) in the sediment column, (iii) suitable environmental isotopes to quantifying the sedimentary organic carbon accumulation, outwelling of the carbon-containing byproducts of decomposition of biogenic organic matter and acid neutralizing alkalinity produced in situ sediment to the offshore. Above-ground biomass is not cumulative over the years except for mangrove forests within coastal blue carbon systems. Non-gaseous carbon sequestration and loss occur mainly as a form of sediment organic carbon (SOC) and dissolved carbon in an intertidal and subtidal bottom sediment body in a slow, patchy, and dispersive way, on which this article focuses. Investigating environmental radionuclides is probably the most cost-effective effort to contribute to defining the offshore spatial extent of coastal blue carbon systems except for seagrass beds (e.g., Ra isotopes), to quantify millimeter per year scale carbon accretion and loss within the systems (e.g., 7 Be, 210 Pb) and a liter per meter of coastline per a day scale water movement from the systems (Ra isotopes). A millimeter-scale spatial and an annual (or less) time-scale resolution offered by the use of environmental isotopes would equip us with a novel tool to enhance the carbon storage capacity of the coastal blue carbon system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

2-Aminobenzothiazoles are widely used in the fields of pharmaceuticals and pesticides. Herein, we report a metal-free protocol for the preparation of 2-aminobenzothiazoles by a covalent organic framework (COF) catalyzed tandem reaction. In the presence of catalytic amount of phenanthroline-decorated COF (Phen-COF), a variety of 2-aminobenzothiazoles are obtained in excellent yields by the cross-coupling of 2-iodoanilines with isothiocyanates at room temperature in water. In addition, the COF-catalyst is very stable and can be reused at least seven times without loss of its catalytic activity., (© 2023 Wiley‐VCH GmbH.)

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Covalent organic frameworks (COFs) have recently drawn intense attention due to their potential applications in photocatalysis. Herein, we report a multifunctional COF which consists of triphenylamine (TPA) and 2,2'-bipyridine (2, 2'-bipy) entities. The obtained TAPA-BPy-COF is a heterogeneous photocatalyst and can efficiently catalyze the oxidative coupling of thiols to disulfides. In addition, TAPA-BPy-COF can be further metalated by Pd(II) via 2,2'-bipy-metal coordination. The generated Pd@TAPA-BPy-COF can highly promote photocatalytic synthesis of 3-cyanopyridines via cascade addition/cyclization of arylboronic acids with γ-ketodinitriles in heterogeneous way. This work has demonstrated the way for the rational design and preparation of more efficient photoactive COFs for photocatalysis., (© 2023 Wiley-VCH GmbH.)

Aim: To investigate the incidence and high-risk factors associated with the surgical treatment of acute female pelvic inflammatory disease (PID)., Methods: A retrospective analysis was conducted on all inpatients diagnosed with acute female PID, encompassing conditions such as endometritis, salpingitis, tubo-ovarian abscess, ovarian abscess, and pelvic peritonitis, at Dongyang Hospital of Wenzhou Medical University from January 2013 to December 2021. Patients were categorized into two groups: the surgery group (n = 58) and the non-surgery group (n = 399), based on the necessity of surgical intervention (refer to Materials and Methods for surgical indications). Collected data included patient demographics (age, body mass index (BMI)), comorbidities (hypertension, diabetes mellitus), initial laboratory findings upon admission (white blood cell count, absolute neutrophil count, hemoglobin, platelet count, blood urea nitrogen/creatinine, prothrombin time (PT), international normalized ratio (INR), fibrinogen, albumin), surgical records, and postoperative pathology. Univariate and multivariate logistic regression analyses were conducted to ascertain the risk factors associated with the surgical treatment of acute female PID., Results: Out of 457 hospitalized patients with acute female PID, 58 cases (12.7%) required surgical intervention. Univariate and multivariate logistic regression analyses indicated that advancing age correlated with an increased likelihood of surgical intervention in women with acute PID (odds ratio (OR) = 1.052, 95% Confidence Interval (CI) 1.022-1.082, p = 0.001). Additionally, lower serum albumin levels upon admission were associated with a heightened risk of surgery (OR = 0.913, 95% CI 0.859-0.970, p = 0.003), while elevated fibrinogen levels amplified the risk of surgical intervention in these patients (OR = 1.193, 95% CI 1.008-1.411, p = 0.04)., Conclusions: Elderly women diagnosed with acute PID, especially those presenting with abscess formation, should undergo prompt surgical intervention if they display high-risk factors such as low albumin levels and elevated fibrinogen levels upon admission.

Although some studies have reported on the levels and clinical significance of peripheral blood neutrophil/lymphocyte ratio (NLR) in cervical cancer, the role of NLR levels and their changes preoperatively and postoperatively in early cervical cancer remain unclear. Our analyses explored the preoperative and postoperative NLR in 203 patients with stage I-IIA cervical cancer and evaluated the relationship between NLR changes, clinicopathological characteristics, and patient prognosis. The cut-off preoperative and postoperative NLR values were determined using receiver operating characteristic curve analysis. Preoperative NLR correlated with age, menopausal status, tumor size, and vascular infiltration, whereas postoperative NLR correlated with tumor differentiation. Patients with cervical cancer with a high preoperative NLR had significantly shorter overall survival (OS) and progression-free survival (PFS) than other patients, whereas PFS was significantly lower in the high postoperative NLR group. When comparing postoperative and preoperative NLR values, we observed a significantly higher rate of increase in postmenopausal patients and those without vascular infiltration than that among premenopausal patients and those with vascular infiltration. However, no clear difference in prognosis was observed between the groups with increased and decreased NLR. Therefore, a high peripheral blood NLR may predict a poor prognosis in patients with early cervical cancer. The effect of NLR changes on the prognosis of patients with cervical cancer requires further verification in multicenter studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Zhang, Wang, Zhu, Xu, Yang, Han and Hu.)

Background: This article describes a systematic review evaluating the effectiveness of training on the humanistic care abilities of nurses., Method: The literature search was conducted in electronic databases to identify studies that evaluated the effect of training on the humanistic care abilities of nurses. Study selection was based on precise eligibility criteria. After the systematic review, a meta-analysis of standardized mean differences ( SMDs ) between posttraining and pretraining humanistic care scale scores was performed to evaluate the effect of training., Results: A total of 11 studies were included (624 nurse participants; 97% women; weighted average age = 38.4 years; 95% confidence interval (CI) [31.5, 45.4]). Training schedules varied and ranged from a full-day workshop to brief weekly sessions for up to 2 months. The training framework involved compassion and empathy communication in most of the included studies. Training improved the humanistic care scale scores of the participants (S MD = 1.171; 95% CI [0.626, 1.716]; p < .0001), whereas no significant change was seen in the scores of control subjects (S MD = 0.588; 95% CI [-0.536, 1.713]; p = .305). The effect of training was observable for up to 1 year, although few studies carried out follow-up evaluations., Conclusion: Training has the potential to improve the humanistic care abilities of nurses. [ J Contin Educ Nurs. 2023;54(9):430-436.] .

Diabetic cardiomyopathy (DCM) is ventricular dysfunction that occurs in patients with diabetes mellitus (DM), independent of recognized risk factors, such as coronary artery disease, hypertension, and valvular heart disease. Dual-specificity phosphatase 12 (DUSP12) is a dual-specificity phosphatase expressed in all tissues. Genome-wide linkage studies have found an association between DUSP12 and type 2 diabetes (T2D). However, the role of DUSP12 in DCM remains largely unknown. Ubiquitously expressed DUSP12 is involved in nonalcoholic fatty liver disease, bacterial infection, and myocardial hypertrophy and plays a critical role in tumorigenesis. Herein, we observed an increased expression of DUSP12 in a hyperglycemia cell model and a high-fat diet (HFD) mouse model. Heart-specific DUSP12-deficient mice showed severe cardiac dysfunction and remodeling induced by an HFD. DUSP12 deficiency exacerbated oxidative stress injury and apoptosis, whereas DUSP12 overexpression had the opposite effect. At the molecular level, DUSP12 physically bound to apoptotic signal-regulated kinase 1 (ASK1), promoted its dephosphorylation, and inhibited its action on c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Rescue experiments have shown that oxidative stress injury and apoptosis, exacerbated by DUSP12 deficiency, are alleviated by ASK1 inhibition. Therefore, we consider DUSP12 an important signaling pathway in DCM., Competing Interests: Declaration of competing interest The authors indicate no potential conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Although chiral covalent organic frameworks (CCOFs) presence grows in thermal asymmetric catalysis, their application in equally important asymmetric photocatalysis has yet to begin. Herein, we first report a propargylamine-linked and quaternary ammonium bromide decorated porphyrin-CCOF which can highly promote visible-light-driven enantioselective photooxidation of sulfides to sulfoxides in water and in air. This methodology has also been applied to the synthesis of ( R )-modafinil, a wakefulness-promoting medication used for the treatment of excessive sleepiness. This research might open a new way for the application of CCOFs in asymmetric photocatalysis.

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties., (© 2019 Wiley Periodicals, Inc.)

Objective: To investigate the value of acoustic parameters in the voice therapy for patients with unilateral vocal cord paralysis (UVCP). Methods: From May 2015 to April 2018, 51 patients with UVCP and 59 healthy controls in Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, were involved in this research retrospectively. The UVCP patients were diagnosed with stroboscopic laryngoscopy. The minimum glottal area (MGA) was calculated by KIPS software when the people were pronouncing/i:/. The fundamental frequency (F0), Jitter, Shimmer and NHR were detected by CSL4500 multiple acoustic voice analyzer. Results: MGA of UVCP patients was much higher than that of healthy control (male: 433.68±64.52 vs . 294.41±51.82, t=9.23, P= 0.000; female: 498.80±73.42 vs . 302.03±76.54, t=13.21, P= 0.000), which meaned vocal cord insufficiency.After voice therapy, MGA reduced significantly (male: 288.48±55.09, female: 258.22±57.17, t =24.41 and 31.22, P= 0.000 vs. pre-therapy). MGA of untreated patients decreased in varying degrees. Compared with the voice therapy group, the MGA decreased in a significantly lower extent (24.25±22.91 vs . 188.31±54.37, t=8.97, P= 0.000). The F0, Jitter, Shimmer and NHR raised significantly in UVCP patients group ( P= 0.000 vs. healthy control group), and they were reduced by voice therapy (all P <0.05). Each of the four acoustic parameters was relative with MGA, r =0.551, 0.867, 0.853 and 0.875 in turn, P= 0.001, 0.000, 0.000, and 0.000. Conclusion: MGA and acoustic parameters can reflect the acoustic features of UVCP patients, which are useful tools in the UVCP assessment and voice therapy.

Six new metal-organic coordination polymers (CPs) [Ni(L)(2,5-TDC)(H 2 O)] n (1), [Ni(L)(1,3-BDC)(H 2 O)] n (2), [Ni(L)(1,4-BDC)(H 2 O)] n (3), [Mn(L)(2,5-TDC)(H 2 O)] n (4), [Mn(L)(2,6-PYDC)(H 2 O)] n (5) and [Mn(L)(1,4-NDC)] n (6) were achieved by reactions of the corresponding metal salt with mixed organic ligands (L = 3,6-bis(benzimidazol-1-yl)pyridazine, 2,5-H 2 TDC = thiophene-2,5-dicarboxylic acid, 1,3-H 2 BDC = isophthalic acid, 1,4-H 2 BDC = terephthalic acid, 2,6-H 2 PYDC = pyridine-2,6-dicarboxylic acid, 1,4-H 2 NDC = naphthalene-1,4-dicarboxylic acid) under solvothermal condition. CPs 1-6 were characterized by single-crystal X-ray diffraction, IR, TG, XRD and elemental analyses. Their structures range from the intricate 3D CPs 1, 3, 4 and 6 to the 2D coordination polymer 2 and the infinite 1D chain 5. The CPs 1-4 and 6 underlying networks were classified from the topological viewpoint, disclosing the distinct sql (in 1), pcu (in 3 and 6), new topology (in 2), and dia (in 4) topological nets. Moreover, analysis of thermal stability shows that they had good thermal stability. Finally, magnetic properties of CPs 1-6 have been studied, the results showed that complex 2 had ferromagnetic coupling and complexes 1, 3-6 were antiferromagnetic., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Fused-thiophene discotic liquid crystals were designed and easily synthesized by Suzuki coupling and FeCl 3 oxidized tandem cyclodehydrogenation reactions, including homo- and cross-coupling reactions. The resulting hexagonal and rectangular columnar mesomorphic supramolecular structures formed were characterized by polarizing optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering. The charge carrier transport properties in the mesophases of two of the synthesized fused-thiophene discogens were measured by transient photocurrent time-of-flight (TOF) technique, revealing fast hole transport values in the range of 10 -3 to 10 -2  cm 2  V -1  s -1 , thus demonstrating potential applications in electronic devices. The luminescent sanidic mesogens, with different extended π-conjugated systems, also emit blue, green, or red light, with absolute photoluminescent quantum yields as high as 18 %., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the role of the lateral reticular nucleus (LRN) in descending inhibition of cardiac nociception in rats and the involvement of spinal serotonergic receptors in the descending inhibition., Methods: Male SD rats were randomly divided into 5 groups, namely bradykinin (BK) group, BK + glutamate group, BK + methysergide group, BK + glutamate + methysergide group, and BK + glutamate + vehicle group. The rats received glutamate microinjection in the LRN combined with the intrathecal injection of serotonergic receptor antagonist methysergide, and the changes in the cardiacsomatic motor reflex induced by intrapericardial BK injection were monitored by observing electromyogram (EMG) responses of the dorsal spinotrapezius muscle; c-Fos expression in the spinal dorsal horn was also tested., Results: Compared with BK group, intra-LRN glutamate administration produced a significant inhibitory effect on intrapericardial BK-induced EMG in a dose-dependent manner, and c-Fos expression was significantly decreased in the spinal dorsal horn (P<0.05). Compared with BK + glutamate group, intrathecal administration of methysergide significantly attenuated the inhibitory effect of chemical stimulation of the LRN on intrapericardial BK-induced EMG and increased c-Fos expression in the spinal dorsal horn (P<0.05). Intrathecal administration of the vehicle did not produce any effect on EMG or c-Fos expression (P>0.05)., Conclusion: The serotonergic receptors in the spinal cord are involved in LRN-mediated descending inhibition of cardiac nociception in rats.

Objective: To explore the application of narrow band imaging(NBI) technology in laryngeal tumor. Method: From Appril 2014 to Otober 2016, three hundred and twenty-two patients with suspected laryngeal cancer or precancerous lesions were enrolled in the First Central Hospital of Tianjin. Each patient was examined by electronic nasopharyngolaryngoscope under white light and NBI model. The sensitivity, specificity and accuracy of laryngeal tumor diagnosis under white light mode and NBI mode was compared based on pathological results. Result: The sensitivity, specificity and accuracy of white light mode in laryngeal tumor diagnosis were 77.17%,62.07% and 74.36%, respectively whereas the NBI model were 92.91%,77.59% and 90.06%, respectively.The sensitivity and accuracy of NBI model in laryngeal tumor diagnosis were significantly higer than white light model( P <0.05),but not the specificity. Conclusion: The electronic nasopharyngolaryngoscope of NBI technology not only found early lesions of laryngeal cancer, but also can improve the sensitivity and accuracy of laryngeal tumor diagnosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The Korteweg-de Vries (KdV)-type models have been shown to describe many important physical situations such as fluid flows, plasma physics, and solid state physics. In this paper, a new (2 + 1)-dimensional KdV equation is discussed. Based on the Hirota's bilinear form and a generalized three-wave approach, we obtain new exact solutions for the new (2 + 1)-dimensional KdV equation. With the help of symbolic computation, the properties for some new solutions are presented with some figures.

The ventrolateral periaqueductal gray (vlPAG) is an important brain area, in which 5-HTergic neurons play key roles in descending pain modulation. It has been proposed that opioid peptides within the vlPAG can excite the 5-HTergic neurons by alleviating tonic inhibition from GABAergic neurons, the so-called disinhibitory effect. However, no direct morphological evidence has been observed for the micro-circuitry among the opioid peptide-, GABA-, and 5-HT-immunoreactive (ir) profiles nor for the functional involvement of the opioid peptides in the intrinsic properties of GABAergic and 5-HTergic neurons. In the present study, through microscopic observation of triple-immunofluorescence, we firstly identified the circuitry among the endomorphin-1 (EM1, an endogenous ligand for the μ-opioid receptor)-ir terminals and GABA-ir and 5-HT-ir neurons within the rat vlPAG. The synaptic connections of these neurons were further confirmed by electron microscopy. Through the in vitro whole-cell patch-clamp method, we showed that EM1 has strong inhibitory effects on the spiking of GABAergic neurons. However, although the resting membrane potential was hyperpolarized, EM1 actually increased the firing of 5-HTergic neurons. More interestingly, EM1 strongly inhibited the excitatory input to GABAergic neurons, as well as the inhibitory input to 5-HTergic neurons. Finally, behavioral results showed that pretreatment with a GABA(A) receptor antagonist potentiated the analgesic effect of EM1, while treatment with a GABA(A) receptor agonist blocked its analgesic effect. In summary, by utilizing morphological and functional methods, we found that the analgesic effect of EM1 is largely dependent on its potent inhibition on the inhibitory inputs to 5-HTergic neurons, which overwhelms EM1's direct inhibitory effect on 5-HTergic neurons.

Vegetation plays an important role in regulating the terrestrial carbon balance and the climate system, and also overwhelmingly dominates the provisioning of ecosystem services. Therefore, it has significance to monitor the growth of vegetation. Based on AVHRR GIMMS NDVI and MODIS NDVI datasets, we analyzed the spatiotemporal patterns of change in NDVI and their linkage with climate change and human activity from 1982 to 2012 in the typical arid region, Xinjiang of northwestern China, at pixel and regional scales. At regional scale, although a statistically significant positive trend of growing season NDVI with a rate of 4.09 x 10⁻⁴· a⁻¹ was found during 1982-2012, there were two distinct periods with opposite trends in growing season NDVI before and after 1998, respectively. NDVI in growing season first significantly increased with a rate of 10 x 10⁻⁴· a⁻¹ from 1982 to 1998, and then decreased with a rate of -3 x 10⁻⁴· a⁻¹ from 1998 to 2012. The change in trend of NDVI from increase to decrease mainly occurred in summer, followed by autumn, and the reversal wasn't observed in spring. At pixel scale, the NDVI in farmland significantly increased; the NDVI changes in the growing season and all seasons showed polarization: Areas with significant change mostly increased in size as the NDVI record grown in length. The rate of increase in size of areas with significantly decreasing NDVI was larger than that with significantly increasing NDVI, which led to the NDVI increase obviously slowing down or stopping at regional scale. The vegetation growth in the study area was regulated by both climate change and human activity. Temperature was the most important driving factor in spring and autumn, whereas precipitation in summer. Extensive use of fertilizers and increased farmland irrigated area promoted the vegetation growth. However, the rapid increase in the proportion of cotton cultivation and use of drip irrigation might reduce spring NDVI in the part of farmlands, and the increase in stocking levels of livestock might lead to a decrease in NDVI in some grasslands.

Numerous studies have evaluated the association between TCF7L2 gene polymorphisms (rs12255372 and rs7903146) and breast cancer risk. However, the results have been inconsistent. Therefore, in the current study, we performed a meta-analysis. A systematically literature search of the PubMed and EMBASE databases was conducted in November 2013, and the reference lists of articles were retrieved. A summary odds ratio (OR) with its 95% confidence interval (CI) were calculated to evaluate the strength of association. Publication bias was investigated using Begg's funnel plot. Meta-analysis was performed using STATA package version 12.0. A total of 4 case-control studies met our inclusion criteria, including 4600 cases and 5289 controls. Overall, TCF7L2 gene polymorphisms were significantly associated with an increased risk of breast cancer in genetic comparison models (rs12255372 for GG vs GT: OR = 0.90, 95%CI = 0.83-0.98; rs7903146 for CC vs TT: OR = 0.75, 95%CI = 0.63-0.90, CC vs CT: OR = 0.88, 95%CI = 0.81-0.97, dominant model: OR = 1.16, 95%CI = 1.06-1.27, recessive model: OR = 0.79, 95%CI = 0.67-0.94). This meta-analysis demonstrated that TCF7L2 gene polymorphisms (rs12255372 and rs7903146) are associated with an increased susceptibility to breast cancer. However, further studies including large sample sizes are needed to validate this association.

Angina pectoris is a common clinical symptom that often results from myocardial infarction. One typical characteristic of angina pectoris is that the pain does not match the severity of the myocardial ischemia. One possible explanation is that the intensity of cardiac nociceptive information could be dynamically regulated by certain brain areas. As an important nucleus for processing cardiac nociception, the nucleus of the solitary tract (NTS) has been studied to some extent. However, until now, the morphological and functional involvement of the NTS in chronic myocardial infarction (CMI) has remained unknown. In the present study, by exploring left anterior descending coronary artery ligation surgery, we found that the number of synaptophysin-immunoreactive puncta and Fos-immunoreactive neurons in the rat NTS two weeks after ligation surgery increased significantly. Excitatory pre- and postsynaptic transmission was potentiated. A bath application of a Ca2+ channel inhibitor GABApentin and Ca2+ permeable AMPA receptor antagonist NASPM could reverse the potentiated pre- and postsynaptic transmission, respectively. Meanwhile, rats with CMI showed significantly increased visceral pain behaviors. Microinjection of GABApentin or NASPM into the NTS decreased the CMI-induced visceral pain behaviors. In sum, our results suggest that the NTS is an important area for the process of cardiac afference in chronic myocardial infarction condition.

Objective: Examine the effect of electrical stimulation of nucleus tractus solitaries (NTS) on cardiac-somatic motor reflex (CMR) that induced by intrapericardial administration of capsaicin to clarify the spinal cord mechanism of NTS involved in cardiac nociception in rat., Methods: SD rats were randomly divided into electrical stimulation, control, yohimbine and naloxone group and treated with elecetrical stimulation NTS alone, or with intrathecal injection of vehicle, saline, norepinephrine a2 receptors antagonist (yohimbine), opioid receptor antagonist (naloxone) respectively., Results: Electrical stimulation of NTS (10, 20, 50 MA), the CMR response deceased in an intensity-dependent manner (P<0.05); intrathecal injection of vehicle, saline had no effect on the inhibition effect of electrical stimulation (P>0.05); intrathecal injection of yohimbine (20 microg, 50 microg) or naloxone (50 microg, 100 microg), reversed the inhibition effect of electrical stimulation (P<0.05); intrathecal injection of low dose of naloxone, the inhibition effect of electrical stimulation was potentiated., Conclusion: Electrical stimulation of NTS has inhibition effect on cardiac nociception, norepinephrine alpha2 receptors and opioid receptor in spinal cord involved in this descending inhibition, low dose of naloxone has synergetic effect with descending inhibition.

Background: Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis., Methods: The myocardial infarction (MI) mice model was induced and cardiac fibroblasts were cultured. Histological analyses, quantitative real-time polymerase chain reaction and Western blotting analysis were used., Results: We found that the miR-34 cluster, especially miR-34a, was upregulated in the MI heart. In vivo, inhibition of miR-34a reduces the severity of experimental cardiac fibrosis in mice. TGF-β1 increased miR-34a expression in cardiac fibroblasts. Overexpressing miR-34a levels increased the profibrogenic activity of TGF-β1 in cardiac fibroblast, whereas inhibition miR-34a levels weakened the activity. Finally, we showed that miR-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of Smad4 expression., Conclusions: Our findings provide evidence that miR-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting Smad4, which suggests that miR-34a may be new marker for cardiac fibrosis progression and that inhibition of miR-34a may be a promising strategy in the treatment of cardiac fibrosis.

Objective: To study effects of body mass index (BMI) on postoperative outcome in patients with osteoarthritis after total knee arthroplasty (TKA)., Methods: The data of 148 patients with osteoarthritis who underwent TKA from June 2006 to May 2009 in our hospital and had complete follow-up data were analyzed restrospectively, including 29 males and 119 females, ranging in age from 39 to 89 years old, with an average age of 71.2 years old. According to BMI classification standard, all the patients were divided into 4 groups: non-obese group (BMI ≤ 25.0 kg/m2), had 38 patients (45 knees), including 9 males and 29 females, with a mean age of (70.0 ± 8.2) years old; overweight group (BMI 25.1 to 27.0 kg/m2), had 40 patients (48 knees), including 10 males and 30 females, with a mean age of (72.6 ± 7.4) years old; obesity group (BMI 27.1 to 30.0 kg/ m2), had 30 patients (43 knees), including 7 males and 30 females, with a mean age of (70.4 ± 6.0) years old; morbidly obesity group (BMI > 30.0 kg/m2), 33 patients (39 knees), including 3 males and 30 females, with a mean age of (71.7 ± 6.4) years old. The index such as Knee Society Score (KSS), anterior knee pain and patella cartilage damage during surgery were recorded before surgery and at the time of follow-up., Results: Postoperative KSS increased significantly compared to preoperative KSS, and the good rate reached to 97.1%. In the knee score, preoperative KSS and postoperative KSS had no significant differences among the four groups (preoperative P = -0.789; postoperative P = 0.133). However, compared with other groups, obesity group got the lowest preoperative function score (preoperative P = 0.036; postoperative P = 0.225). While the incidence of anterior knee pain was 9.7% (17/175), including 14 grade I and 3 grade II. There were no significant differences in incidence of anterior knee pain among four groups (χ2 = 0.764, P = 0.862). The average BMI of the patients with anterior knee pain was (27.4 ± 3.6) kg/m2, while the others' BMI was (27.5 ± 4.4) kg/m2. There was no statistically difference between two groups (t = -0.061, P = 0.951). There were no significant differences in patella cartilage damage among groups (χ2 = 7.070, P = 0.314)., Conclusion: The KSS increases in all the different groups. Those patients get the benefit from TKA, and the obese patients can receive a similar postoperative outcome as the non-obese ones.

Objective: To investigate the effect of augmentative locking compression plate combined with bone graft in treating aseptic femoral shaft nonunion after intramedullary nailing., Methods: Twenty-one cases with aseptic femoral shaft nonunion after intramedullary nailing from January 2007 to January 2013 were treated,including 18 males and 3 females with a mean age of 37.7 years (ranged from 23 to 64 years). The mean period of nonunion after surgery was 23.9 months (ranged from 9 to 62 months). According to Weber-Cech classification,10 of those 21 cases were hypertrophic nonunion,7 were atrophic, and 4 had oligotrophic fracture nonunion. All patients retained the original intramedullary nail, and applied with augmentation plating of 6 to 8 holes locking compression plate, unicortical fixation with 2 to 3 locking screws in the proximal or distal end, with simultaneous autologous iliac bone grafting. After treatment,all patients were allowed to partial weight-bearing until full weight-bearing according to the radiological results. All patients were followed up and were evaluated with clinical and imaging results., Results: All patients were followed up from 8 to 24 months, averaged (13.5±3.5) months,which showed clinical union at 4 to 8 months, averaged (6.0±1.0) months and radiological solid union at 7 to 12 months, averaged (9.1±1.5) months. No such complications as infection,hardware loosening or breaking were found., Conclusion: Augmentative locking compression plate(LCP) combined with bone graft for aseptic femoral shaft nonunion after intramedullary nail has a satisfied clinical efficacy. It's an useful and simple method.

A new method of near-infrared (NIR) diffuse reflectance spectroscopy is proposed to rapidly determine the degree of polymerization (DP) of natural cellulose (cotton and wood) pulp produced by a new clean pulping process. One hundred and ninety five samples were collected and their DP data were determined by standard method GB/T 9107-1999. The spectroscopy measurement method of the samples was studied and their near-infrared diffuse reflectance spectra were collected. The quantitative DP calibration models of one mixed cotton & wood and two separate cotton and wood pulps were established by partial least squares (PLS). The optimum models were developed using the spectra pretreated by derivative, autoscaling and mean-centering, and their performance is as follows: correlation coefficient of 0.980, 0.993 and 0.886, and RMSEP of 147, 143 and 53, respectively. The accuracy of NIR method was also studied. The results show that the accuracy of the two separate models of cotton and wood is better than that of the mixed model, and the precision of the two separate models is better than that of GB/T9107-1999. The identification model of cotton and wood was also established using principal component analysis (PCA). The result shows that the spectra of cotton and wood pulp have obvious difference, and the model can identify successfully the two kinds of pulp. The result indicates that the new NIR method is feasible to realize the on-line analysis of polymerization degree of natural cellulose pulp with its advantage of rapidness and easy operation.

Objective: To observe the effect of cold or hot properties of traditional Chinese medicines (TCM) on biological effect indexes, and analyze the contribution of variables on cold or hot properties, in order to preliminarily establish the discrimination mode for the biological effects of cold or hot properties., Method: Rats were randomly divided into the blank control group, cold TCM groups (Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix and Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex and Evodiae Fructus), and orally administered with 10 mL x kg(-1) of corresponding TCM water decoctions for 30 d, twice a day. Altogether 53 biological effect indexes correlated to cold or hot properties of traditional Chinese medicines were founded by searching literatures. The data warehouse were established by using data-mining software Clementine12.0. Data of the blank control group, cold TCM groups (Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix, Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex) were selected into a training set. C5.0 algorithm and C&R classification and regression algorithm were adopted to define the importance of variable, create the decision trees, and test hot or cold properties of Evodiae Fructus and Scutellariae Radix., Result: According to C&R classification and regression algorithm, SDH activity of livers was the most important hot or cold property, with the significance closed to 30%. It was followed by triglyceride, liver Na' -K' -ATPase enzyme, muscle glycogen and platelet distribution width, with the accuracy up to 97.39% in models. C5.0 algorithm showed that liver SDH activity was the most important hot or cold property, with the significance closed to 40%. It was followed by triglyceride, GOT, muscle glycogen and liver Na(+)-K(+)-ATPase enzyme, with the accuracy up to 98.26% in models. The possibilities that Evodiae Fructus is in hot property and Scutellariae Radix is in cold property were 100. 00% and 77.78% by using both C&R classification and regression algorithm and C5.0 algorithm., Conclusion: The SDH activity of liver is the most important biological effect index to distinguish cold and hot properties of TCMs. The discrimination pathway or mode of cold and hot properties is closely related to energy metabolism.

Consistent NDVI time series are basic and prerequisite in long-term monitoring of land surface properties. Advanced very high resolution radiometer (AVHRR) measurements provide the longest records of continuous global satellite measurements sensitive to live green vegetation, and moderate resolution imaging spectroradiometer (MODIS) is more recent typical with high spatial and temporal resolution. Understanding the relationship between the AVHRR-derived NDVI and MODIS NDVI is critical to continued long-term monitoring of ecological resources. NDVI time series acquired by the global inventory modeling and mapping studies (GIMMS) and Terra MODIS were compared over the same time periods from 2000 to 2006 at four scales of Qinghai-Tibet Plateau (whole region, sub-region, biome and pixel) to assess the level of agreement in terms of absolute values and dynamic change by independently assessing the performance of GIMMS and MODIS NDVI and using 495 Landsat samples of 20 km x20 km covering major land cover type. High correlations existed between the two datasets at the four scales, indicating their mostly equal capability of capturing seasonal and monthly phenological variations (mostly at 0. 001 significance level). Simi- larities of the two datasets differed significantly among different vegetation types. The relative low correlation coefficients and large difference of NDVI value between the two datasets were found among dense vegetation types including broadleaf forest and needleleaf forest, yet the correlations were strong and the deviations were small in more homogeneous vegetation types, such as meadow, steppe and crop. 82% of study area was characterized by strong consistency between GIMMS and MODIS NDVI at pixel scale. In the Landsat NDVI vs. GIMMS and MODIS NDVI comparison of absolute values, the MODIS NDVI performed slightly better than GIMMS NDVI, whereas in the comparison of temporal change values, the GIMMS data set performed best. Similar with comparison results of GIMMS and MODIS NDVI, the consistency across the three datasets was clearly different among various vegetation types. In dynamic changes, differences between Landsat and MODIS NDVI were smaller than Landsat NDVI vs. GIMMS NDVI for forest, but Landsat and GIMMS NDVI agreed better for grass and crop. The results suggested that spatial patterns and dynamic trends of GIMMS NDVI were found to be in overall acceptable agreement with MODIS NDVI. It might be feasible to successfully integrate historical GIMMS and more recent MODIS NDVI to provide continuity of NDVI products. The accuracy of merging AVHRR historical data recorded with more modern MODIS NDVI data strongly depends on vegetation type, season and phenological period, and spatial scale. The integration of the two datasets for needleleaf forest, broadleaf forest, and for all vegetation types in the phenological transition periods in spring and autumn should be treated with caution.

The present study examined the role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of noradrenaline (1, 2, 4 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, reduced allodynia; PWT increased in a dose-dependent manner. Similar to noradrenaline, microinjection of selective α₂ adrenoceptor agonist clonidine into the same VLO site also reduced allodynia, and was blocked by selective α₂ adrenoceptor antagonist yohimbine. Furthermore, administration of γ-aminobutyric acid A (GABAA) receptor antagonist bicuculline or picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine-induced inhibition. These results suggest that noradrenaline acting in the VLO can potentially reduce allodynia induced by SNI, and this effect is mediated by α₂ adrenoceptor. Moreover, GABAergic disinhibition may participate in α₂ receptor mediating effects in neuropathic pain in the central nervous system., (© 2013.)

Objective: To determine the effects of NMDA and NK1 receptor agonist and antagonist on the EMG and the synaptic mechanism of nociceptive information transmissions in the spinal cords., Methods: Male SD rats were randomly divided into seven groups, with intrathecal injection of the following chemicals respectively: control group (10 microL saline), NMDA group (0.147 microg/10 pL NMDA), MK801 group (6.8 microg/10 microL MK801), MK801+NMDA group (6.8 microg/10 pL MK801+0. 147 microg/10 pL NMDA), Sar-SP group (1.4 pg/10 microL Sar-SP), CP-96345 group (5 microg/10 pL CP-96345), and CP-96345+Sar-SP group (1.4 micro/10 microL Sar-SP+5 microg/10 microL CP-96345). A cardiac pain model in rats through intrapericardial injection of capsaicin was established. Intrapericardial injection of capsaicin was given to the rats 10 min after intrathecal injection of the tested chemicals. The spinotrapezius electromyography (EMG) activities as an index of cardiac-somatic motor reflex were recorded simultaneously., Results: Compared with the pre-test controls (100%), saline did not make a significant change to the capsaicin-evoked EMG response (96. 9% +/- 12. 5%, P>0. 05); NMDA agonist increased the capsaicin-evoked EMG response (185. 2% +/- 24. 4%) significantly (P<0. 05); neither MK801 nor a combined administration of MK801 and NMDA made a significant change to the capsaicin-evoked EMG response (106. 6% +/- 10. 2%, P> 0.05); Sar-SP increased the capsaicin-evoked EMG response (145. 6% 10. 1%) significantly (P<0. 05); whereas neither CP-96345 nor a combined administration of CP-96345 and Sar-SP made a significant change to the capsaicin-evoked EMG response (102. 2% +/- 8. 4%, P>0.05)., Conclusion: NMDA and NK1 receptors may have participated in the transmissions of cardiac nociception information in the spinal cords of rats.

The present study examined the roles of ventrolateral orbital cortex (VLO) 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptor subtypes in mediating 5-HT-induced antiallodynic actions in the rat spared nerve injury (SNI) pain model. Changes in paw withdrawal threshold (PWT) were measured using von-Frey filaments. Microinjection of 5-HT (2, 5 and 10μg, in 0.5μl) into the VLO depressed allodynia induced by SNI, and the PWT increased in a dose-dependent manner. Microinjection of selective 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT5A, 5-HT6 and 5-HT7 receptor antagonists, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190) (10μg), cyproheptadine (50ng), granisetron hydrochloride (granisetron) (10μg), 1-[2-[(methylsulfonyl)-amino]ethyl]-4-piperidinyl]methyl1-methyl-1H-indole-3-carboxylate (GR113808) (5μg), SB699551 dihydrochloride (SB699551) (10μg), SB258585 dihydrochloride (SB258585) (2μg) or SB269970 hydrochloride (SB269970) (10μg) into the VLO 5-min prior to 5-HT (10μg) injection, all antagonized the 5-HT-induced inhibition of allodynia. In addition, these antagonists applied alone to VLO did not influence allodynia. These results suggest that although 5-HT1-7 receptor subtypes in the VLO do not have a tonic modulatory action on the allodynia induced by SNI, they are involved in mediating the depression of the SNI allodynia produced by injection of 5HT into VLO., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

The current study examined the role of the lateral reticular nucleus (LRN) in modulating the cardiosomatic reflex (CSR) induced by intrapericardial capsaicin in the anesthetized rat. Intrapericardial capsaicin was administered, and the CSR was monitored via electromyogram responses of the dorsal spinotrapezius muscle. Electrical stimulation of the LRN (10, 20 and 30 μA) depressed the CSR induced by intrapericardial capsaicin in an intensity-dependent manner. Microinjection of glutamate (4, 10, 20 and 40 nmol, in 0.2 μL) into the LRN replicated the effects of electrical stimulation. Furthermore, bilateral transections of the dorsolateral funiculus (DLF) decreased the LRN electrical stimulation-induced inhibition of the electromyogram responses. Intrathecal administration of the α2 -adrenergic receptor antagonist yohimbine or the serotonergic receptor antagonist methysergide significantly attenuated the LRN electrical stimulation-induced inhibition of the electromyogram responses. However, intrathecal application of the opioid receptor antagonist naloxone had no effect on the LRN electrical stimulation-induced inhibition. These results suggest that the LRN-DLF-spinal cord pathway is involved in descending inhibition of the CSR, and spinal α2 -adrenergic and serotonergic receptors participate in this descending inhibition., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Simultaneously, emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). We tested the hypothesis that sEHi could reduce the occurrence of ACS by regulating FAS., Methods: Hospitalized ACS patients were selected as the ACS group (n = 65) while healthy normal subjects as the control group (n = 65). The blood levels of lipoproteins, fasting glucose, myocardial enzyme and high-sensitivity C-reactive protein (hs-CRP) were measured within 24 hours after admission. The peripheral blood mononuclear cells (PBMCs) were isolated and cultured. Trans-4-[4-(3-Adamantan-1-ylureido)cyclohexyloxy] benzoic acid (t-AUCB), a kind of sEHi, was then added to cells in various concentrations (0, 10, 50, 100 μmol/L). The expression of FAS, interleukin-6 (IL-6) mRNA and protein was detected by real-time PCR or Western blot, respectively., Results: (1) Compared with the control group, the serum concentration of hs-CRP in the ACS group was increased (P<0.05). The expression of FAS, IL-6 mRNA and protein were significantly increased in PBMCs from the ACS group (all P<0.05). Moreover, the levels of FAS and IL-6 mRNA were positively correlated with the serum concentration of hs-CRP (r = 0.685, P<0.01; r = 0.715, P<0.01) respectively. (2) The expression of FAS, IL-6 mRNA and protein in PBMCs from the ACS group were dose-dependently inhibited by sEHi (all P<0.05)., Conclusions: sEH inhibition regulated FAS and inhibited inflammation in cultured PBMCs from ACS patients, a mechanism that might prevent rupture of atherosclerotic lesions and protect against development of ACS.

A new near infrared diffuse reflectance spectroscopy method is proposed to rapidly detect alpha-cellulose content of natural cellulose (plant fiber: cotton, wood) pulp in a new clean pulping process. One hundred forty two samples were collected and their alpha-cellulose content data were determined by standard method GB/T 9107-1999. The samples were homogenized by grinding pretreatment to improve spectroscopy measurement accuracy. Effective classification models were built by SIMCA, with the total correct identification. Using partial least squares (PLS) quantitative calibration, alpha-cellulose of the whole and separate cotton and wood pulp was established, with the correlation coefficients of 0.954, 0.911, 0.839, SEP, 0.024, 0.012 and 0.016, respectively. The repeatability results obtained by the new method are in agreement with the results from GB/T 9107-1999. The new method is feasible for determining alpha-cellulose content of natural cellulose (plant fiber: cotton, wood) in clean pulping process.

Recent study from our laboratory has indicated that microinjection of glutamate into the nucleus tractus solitarius (NTS) facilitates the cardiac-somatic reflex induced by pericardial capsaicin. Further, N-methyl-d-aspartate (NMDA) receptors and metabotropic glutamate receptors (mGluRs) mediate this function. However, the roles of the individual receptor subtypes or subunits in modulating cardiac nociception are unknown. Among the three groups of mGluRs, group III mGluRs are the primary mGluR subtype expressed in visceral afferent neurons in the NTS. The present study examined the roles of group III mGluRs and their subtype 7 and 8 receptors (mGluR7 and mGluR8) in modulating the cardiac-somatic reflex induced by pericardial capsaicin, which was monitored by recording electromyogram (EMG) activity from the spinotrapezius muscle in anesthetized rats. Intra-NTS microinjection of a group III mGluR agonist, l-(+)-2-Amino-4-phosphonobutyric acid (l-AP4, at 1, 10, and 20 nmol) or a selective mGluR7 agonist, N,N'-diphenylmethyl-1,2-ethanediamine dihydrochloride (AMN082, at 1, 2, and 4 nmol) both decreased the EMG response in a dose-dependent manner. This decrease was inhibited by the group III mGluR antagonist (RS)-α-Methylserine-O-phosphate (MSOP, at 20 nmol). In contrast, intra-NTS microinjection of a selective mGluR8 agonist, (S)-3, 4-dicarboxyphenylglycine (DCPG, at 6 and 8 nmol), significantly increased the EMG response above control levels. This effect was eliminated by intra-NTS MSOP and by vagal deafferentation. These data suggest that group III mGluRs and mGluR7 in the NTS display an inhibitory effect, while mGluR8 displays a facilitatory effect in modulating cardiac nociception, and this facilitatory effect is dependent on vagal afferents., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Many patients suffer from secondary muscle hyperalgesia after experiencing angina pectoris. In this study, we examined the role of the nucleus tractus solitarius (NTS) and glutamate receptors in modulating cardiac-evoked muscle hyperalgesia induced by pericardial capsaicin, which was monitored by recording electromyogram (EMG) activity from the spinotrapezius muscle in the anesthetized rat. Unilateral chemical lesioning of the commissural NTS with the neurotoxin ibotenic acid significantly depressed the cardiac-somatic reflex; the EMG responses decreased to 56.4 ± 6.9% of that of the controls (5 of 5). Microinjection of the excitatory amino acid glutamate, at 10, 20, and 50 nmol, into the commissural NTS increased the EMG response, in a dose-dependent manner, to 116.9 ± 4.9%, 143.9 ± 10.2%, and 214.2 ± 15.8% (n=8), respectively, of that of the controls. In contrast, microinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a, d]-cyclohepten-5,10-imine maleate (MK-801) at 4 and 6 nmol, decreased the EMG response to 45.2 ± 10.6% and 36.8 ± 14.3%, respectively, of that of the controls (n=8 for each dose). Similarly, the metabotropic glutamate receptor (mGluR) antagonist (RS)-a-methyl-4-carboxyphenylglycine (MCPG), at 2.5 and 5 nmol, decreased the EMG response to 65.2 ± 16.3% and 57.0 ± 4.2%, respectively, of that of the controls. When a combination of MK-801 and MCPG was administrated, the EMG response further decreased to 22.5 ± 13.2% (n=6) of that of the controls. However, administration of a non-NMDA receptor antagonist 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), at 2 and 5 nmol, had no effect on the EMG response. These results suggest that the NTS is involved in the facilitation of the cardiac-somatic reflex, and that the NMDA receptor and mGluRs play an important role in mediating this effect., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: The development of cardiovascular disease has been linked to lowered levels of epoxyeicosatrienoic acids (EETs) in the cardiovascular system. Ischemic cardiomyopathy is caused by atherosclerotic lesions in multi-coronary arteries especially diffusive lesions, which can lead to severe myocardial dysfunction, heart enlargement, heart failure, or arrhythmia, and so on. The EETs are metabolized by the soluble epoxide hydrolase (sEH) encoded by the EPHX2 gene that has several known polymorphisms., Content: The EPHX2 gene polymorphism is associated with sEH catalytic activity and various cardiovascular diseases. sEH is distributed in a variety of organs and tissues and regulated by multiple factors. Research in the area has led to the presence of multiple powerful soluble epoxide hydrolase inhibitors (sEHIs), whose molecular structure and function has been optimized gradually. sEHIs increase EETs' concentration by inhibiting hydration of EETs into their corresponding vicinal diols. EETs are important signaling molecules and known as endothelium-derived hyperpolarizing factors (EDHF). sEHIs have been developed for their ability to prevent atherosclerosis, dilate the coronary artery, promote angiogenesis, ameliorate postischemic recovery of heart contractile function, decrease ischemia/reperfusion injury, modulate postischemic arrhythmia, and prevent heart failure., Summary: sEH is one of the etiological factors of cardiovascular diseases, and plays an important role in the progression of myocardium ischemia. This indicates that sEHIs provide a new method for the prevention and treatment of ischemic cardiomyopathy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the effects of soluble epoxide hydrolase inhibitor (sEHi) on the expressions of fatty acid synthase (FASN) mRNA and protein in peripheral blood mononuclear cell (PBMCs) of patients with acute coronary syndrome (ACS) and to discuss the influences of sEHi in the regulated expression of FASN and inflammatory reaction., Methods: The hospitalized ACS patients were selected as the ACS group (n = 35) while the healthy normal subjects as the control group (n = 30). The levels of lipoproteins, fasting blood glucose, myocardial enzyme and hs-CRP (high-sensitive C-reactive protein) were measured within 24 hours after admission. Meanwhile the PBMCs were separated and cultured and then t-AUCB was added in various concentrations (0, 1, 10, 50, 100 µmol/L). The cellular expressions of FASN, IL-6 mRNA and protein were detected by real-time PCR (polymerase chain reaction) and Western blot respectively., Results: (1) The serum concentration of hs-CRP reached (5.6 ± 4.1) mg/L in the ACS group. And it was obviously higher than (1.3 ± 0.9) mg/L in the control group (P < 0.05). Compared with the control group, the expression levels of FASN, IL-6 mRNA and protein significantly increased in the ACS group (the relative expression amount of FASN mRNA: 1 vs 1.709 ± 0.272, FASN protein: 0.407 ± 0.065 vs 1.298 ± 0.087; relative expression amount of IL-6 mRNA: 1 vs 2.302 ± 0.200, IL-6 protein: 0.715 ± 0.058 vs 1.146 ± 0.083, P < 0.05). Moreover, the levels of FASN and IL-6 mRNA had positive correlations with the serum concentration of hs-CRP (r = 0.714, P < 0.01; r = 0.685, P < 0.01). (2) Compared with the control group (t-AUCB 0 µmol/L), 10, 50, 100 µmol/L t-AUCB had inhibited the expressions quantity of FASN, IL-6 mRNA and protein in PBMCs from the ACS group (P < 0.05). The relative expressions of FASN mRNA in t-AUCB 0, 10, 50, 100 µmol/L group were 1, 0.813 ± 0.038, 0.564 ± 0.100, 0.293 ± 0.043 respectively. The relative expressions of FASN protein in t-AUCB 0, 10, 50 and 100 µmol/L group were 0.957 ± 0.280, 0.935 ± 0.275, 0.855 ± 0.253, 0.685 ± 0.206 respectively., Conclusion: The inflammatory level increases obviously in the ACS group. And the expression level of FASN in PBMCs is closely correlated with the inflammatory level in the ACS patients; t-AUCB may prevent the ruptures of atherosclerotic lesions by regulating FASN and inhibiting inflammatory reactions in ACS patients.

The purpose of the present study was to examine whether the rostroventral portion of the medulla oblongata (RVM) exerts descending modulation on the cardiosomatic motor reflex (CMR) in rats. Capsaicin (1 μg/ml, 0.2 ml) was injected into the pericardial sac as an algesic substance to induce the CMR, which was monitored via electromyogram (EMG) responses of dorsal spinotrapezius muscle to the noxious cardiac stimulus. Descending modulation of the CMR was observed by electrical or chemical stimulation of RVM. Specifically, electrical stimulation of RVM produced facilitatory, inhibitory or biphasic effects on the CMR evoked by noxious cardiac stimulation, depending on stimulation intensity. In addition, glutamate receptor activation in RVM replicated the effects of electrical stimulation. Lidocaine interruption of the ventrolateral funiculus/ventral funiculus (VLF/VF) or transection of the dorsolateral funiculus (DLF) revealed that the descending facilitatory and inhibitory influences from RVM were conveyed via the VLF/VF and DLF, respectively. Furthermore, intrathecal administration of naloxone or yohimbine partly reversed the inhibitory effect of RVM electrical stimulation, suggesting that opioid and noradrenergic systems are involved in descending RVM modulation of the CMR., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes., Methods: 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimulated with 100 µg/L LPS after starved for 24 hours, then tAUCB in various concentrations (1, 10, 50, 100 µmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARγ) antagonist GW9662 (5 µmol/L). 0 µmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter A1(ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγ and ABCA1 in cells were detected by Western blot, the efflux rates of (3)H-cholesterol in cells were detected by means of liquid scintillation counter., Results: tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10, 50, 100 µmol/L tAUCB, cholesterol efflux rates were (5.93 ± 0.66)%, (7.40 ± 0.43)%, (8.30 ± 0.34)%, (9.77 ± 0.42)% respectively, there were significant difference after treated by 10 - 100 µmol/L tAUCB compared with control (5.67 ± 0.17)% (P < 0.05).With the concentration of tAUCB increased, ABCA1, PPARγ mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes., Conclusions: tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

Painless myocardial infarction is a serious complication of diabetes. The present study examined whether cardiac nociception was altered in the streptozotocin-induced diabetic rat model by assessing intrapericardial capsaicin-evoked electromyography (EMG) responses in the spinotrapezius muscle. Somatic sensitivities to mechanical and thermal stimulation of the skin were also determined. Intrapericardial administration of capsaicin evoked a concentration-dependent EMG response, which was reproducible with repeated administration. However, the capsaicin-induced EMG responses were different in streptozotocin-induced diabetic rats and controls. Intrapericardial capsaicin produced fewer EMG responses, which were delayed and reduced in streptozotocin-treated rats compared to controls. Pretreatment with capsazepine, a TRPV1 antagonist, significantly decreased capsaicin-evoked EMG activity in both streptozotocin-treated and control rats. In addition, streptozotocin-treated rats showed a decreased paw withdrawal threshold in response to mechanical stimulation but no change in response to radiant heat stimulation. These results suggest that streptozotocin-induced diabetic rats develop somatic mechanical hypersensitivity (allodynia), but reduced cardiac nociception. Decreased TRPV1 function may contribute to the reduction of cardiac nociception in the diabetic rat., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To observe the effects of soluble epoxide hydrolase inhibitors-tAUCB on the uptake and degradation of ox-LDL in adipocytes., Methods: 3T3-L1 preadipocytes were induced into differentiation and maturation. After a 24-hour starvation, the cells were stimulated with 100 ng/ml LPS and then tAUCB at various concentrations (0 - 100 µmol/L)were added for 24 h, or preincubated with the PPARγ (peroxisome proliferators activated receptor gamma) antagonist GW9662 (5 µmol/L). And the 0 µmol/L tAUCB-treated group was taken as the blank control group. Then the uptake and degradation of ox-LDL in cells were measured by radioligand assay. The mRNA expressions of PPARγ and CD36 were detected by real-time PCR (polymerase chain reaction). And the intracellular levels of protein expression of PPARγ and CD36 were detected by Western blot. While ADP and TNF-α in supernatant were detected by ELISA., Results: tAUCB could dose-dependently increase the uptake and degradation of ox-LDL in adipocytes. When stimulated with 10, 50, 100 µmol/L tAUCB, the uptake levels of ox-LDL were (35.6 ± 1.1)ng/mg, (39.8 ± 1.6) ng/mg, (42.6 ± 1.4) ng/mg cell protein and the degradation levels of ox-LDL (2879 ± 54) ng/mg, (3082 ± 56) ng/mg, (3226 ± 68) ng/mg cell protein. And they were significantly higher than those of the control group (28.9 ± 1.2) ng/mg, (2791 ± 54) ng/mg respectively (all P < 0.05). However, after preincubation of GW9662, the uptake of ox-LDL were decreased to (30.6 ± 1.3) ng/mg, (31.1 ± 1.7) ng/mg, (32.1 ± 1.8) ng/mg cell protein whereas the degradation of ox-LDL decreased to (2788 ± 53) ng/mg, (2824 ± 70) ng/mg, (2874 ± 70) ng/mg cell protein. And the difference was statistically significant when it was compared with the corresponding tAUCB-treated group. With the rising concentration of tAUCB, tAUCB could dose-dependently increase the mRNA and protein expression of CD36 and PPARγ. tAUCB could dose-dependently decrease the levels of TNF-α and increase the levels of ADP in adipocytes. GW9662 could significantly inhibit those effects of tAUCB and reduce the uptake and degradation of ox-LDL and the expression of PPARγ and CD36 in adipocytes., Conclusion: tAUCB can up-regulate the PPARγ expression in adipocytes and promote the uptake and degradation of ox-LDL in adipocytes via PPARγ-CD36 pathway. Meanwhile, the levels of ADP and TNF-α may be mediated through the activation of PPARγ.

Aim: To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells., Methods: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis., Results: LGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production., Conclusion: The activity of LGH00031 at the molecular and cellular level is mediated by ROS.

Polyphenolic compounds usually showed different antioxidant capacities depending on the assay methods used. To determine the possible chemical cause for this assay-dependence, two flavonols, kaempferol and morin, were selected as the model molecules for the comparative investigation between electrochemical and chemical oxidations. The electro-oxidation of the flavonols was studied using cyclic voltammetry and in situ UV-Vis spectroelectrochemical technique with a long-optical-path thin-layer electrolytic cell. The spectral changes recorded in different potentials were compared with those in the chemical oxidation by H(2)O(2) or ABTS(*+) radical in the same thin-layer cell. The 4'-OH group of either sample was first oxidized at lower potentials or induced by H(2)O(2), and in this case kaempferol was somewhat more active than morin. With an additional 2'-OH group, morin underwent the secondary oxidation in moderately higher potentials or by ABTS(*+), showing antioxidant capacity about twice of that of kaempferol. This study clarified that the chemical oxidation of a polyphenolic compound by the oxidants with different reactivities, which corresponded to its electro-oxidation in different anodic peaks, had a difference in number of oxidizable OH-groups, leading to the difference in antioxidant capacity.

Bradykinin is one of metabolites produced during myocardial ischemia and infarction that can activate cardiac spinal (sympathetic) sensory neurons to cause chest pain. The aim of this study was 1) to characterize the responses of thoracic superficial and deeper spinal neurons in rats to intrapericardial administration of bradykinin as a noxious cardiac stimulus; 2) to compare neuronal responses to bradykinin alone and a mixture of algogenic chemicals (serotonin, prostaglandin E(2), histamine, adenosine and bradykinin) used in a previous study. Extracellular potentials of single neurons in the T(3) spinal cord were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml solution of bradykinin (10(-5) M, 1 min). The results showed that 10/33 (30%) superficial and 80/165 (48%) deeper spinal neurons responded to intrapericardial bradykinin. All 10 superficial responsive neurons and 72/80 (90%) deeper neurons were excited; 7 (9%) neurons were inhibited; one neuron showed excitation-inhibition response pattern. Of 72 neurons excited by bradykinin, 35 and 47 neurons exhibited short- and long-lasting responses patterns, respectively. The proportions of response patterns and maximal excitatory responses to bradykinin were similar to effects obtained with a mixture of algogenic chemicals. However, the time to peak (28.3+/-3.1 s) and recovery time of long-lasting excitatory responses to bradykinin alone (125.2+/-8.9 s, n=47) were significantly shorter than the responses of neurons to the algogenic mixture (38.6+/-3.8 s and 187.5+/-18.5 s, n=49, P<0.05). In conclusion, bradykinin might play a key role in spinal processing for cardiac nociception, although other components released during ischemia might affect time characteristics of a subtype of thoracic spinal neurons receiving noxious cardiac input.

The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway to the spinal cord relaying in the periaqueductal gray (PAG). This study examines whether activation of D(1)-like and D(2)-like dopamine receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO, D(2)-like dopamine receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the D(2)-like (D(2)/D(3)) dopamine receptor agonist quinpirole (0.1-2.0 microg), but not D(1)-like (D(1)/D(5)) receptor agonist SKF-38393 (1.0, 5.0 microg), into VLO produced dose-dependent antinociception which was antagonized by the D(2)-like (D(2)/D(3)) receptor antagonist raclopride (1.5 microg). We also found that VLO application of the GABA(A) receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the quinpirole-induced inhibition of the TF reflex, whereas the GABA(A) receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the quinpirole-induced inhibition. These results suggest that D(2)-like, but not D(1)-like, dopamine receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the D(2)-like receptor mediated effect. These findings provide support for the hypothesis that D(2)-like receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal dorsal horn.

Caspase-3 is an attractive therapeutic target for treatment of diseases involving disregulated apoptosis. We report here the mechanism of caspase-3 inactivation by isoquinoline-1,3,4-trione derivatives. Kinetic analysis indicates the compounds can irreversibly inactivate caspase-3 in a 1,4-dithiothreitol (DTT)- and oxygen-dependent manner, implying that a redox cycle might take place in the inactivation process. Reactive oxygen species detection experiments using a chemical indicator, together with electron spin resonance measurement, suggest that ROS can be generated by reaction of isoquinoline-1,3,4-trione derivatives with DTT. Oxygen-free radical scavenger catalase and superoxide dismutase eliciting the inactivation of caspase-3 by the inhibitors confirm that ROS mediates the inactivation process. Crystal structures of caspase-3 in complexes with isoquinoline-1,3,4-trione derivatives show that the catalytic cysteine is oxidized to sulfonic acid (-SO(3)H) and isoquinoline-1,3,4-trione derivatives are bound at the dimer interface of caspase-3. Further mutagenesis study shows that the binding of the inhibitors with caspase-3 appears to be nonspecific. Isoquinoline-1,3,4-trione derivative-catalyzed caspase-3 inactivation could also be observed when DTT is substituted with dihydrolipoic acid, which exists widely in cells and might play an important role in the in vivo inactivation process in which the inhibitors inactivate caspase-3 in cells and then prevent the cells from apoptosis. These results provide valuable information for further development of small molecular inhibitors against caspase-3 or other oxidation-sensitive proteins.