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Depression is closely linked to an imbalance in the autonomic nervous system (ANS). However, the role of this imbalance in mediating the effects of sleep deprivation (SD) and vagus nerve stimulation (VNS) on emotional well-being is not fully understood. A population-based analysis was conducted to explore the relationship between sleep duration, depression scores, and heart rate variability (HRV). Additionally, the chronic SD mouse model was established to assess the impact of preventive transcutaneous auricular VNS (taVNS) on pathological and behavioral changes. Our study found a significant link between sleep duration, depression severity, and HRV. Shorter sleep duration was associated with higher depression scores and lower RMSSD (a measure of HRV). In our rat model, insufficient sleep consistently impaired HRV. This effect was mitigated by taVNS, accompanied by corresponding changes in levels of IL-1β and IL-6, astrocyte and microglia activation, and tail suspension times. Using VNS as a preventive treatment for depression-risk individuals with insufficient sleep shows promise. It not only broadens the potential applications of VNS but also sheds light on its mechanism—particularly its role in enhancing vagal nerve function and balancing the ANS, as evidenced by HRV measurements. [Display omitted] • The imbalance of the autonomic nervous system (ANS) caused by sleep deprivation (SD) mediates the occurrence of depression. • Transcutaneous auricular vagus nerve stimulation (taVNS), by ameliorating ANS, reduces SD-induced depression preventively. • The potential benefits of taVNS can be quantified using heart rate variability, which endows it with new application values. [ABSTRACT FROM AUTHOR]

With the increasing environmental pollution and environmental awareness, ecological efficiency has become a hot issue. Based on the traditional DEA model of unexpected output, a new super data envelopment analysis and slacks-based measure considering undesirable outputs (S-DEA-SBM-UO) efficiency model is proposed. Moreover, the weight S-DEA-SBM-UO (W–S-DEA-SBM-UO) is applied to evaluate the ecological efficiency of industrial enterprises. The experimental results show that the W–S-DEA-SBM-UO can measure the ecological efficiency including unexpected output more effectively than the conventional DEA-SBM to solve unexpected output. Finally, it is suggested that enterprises should make great efforts to improve the ecological efficiency and it is pointed out that the results have strong theoretical significance and research value for ecological improvement. [ABSTRACT FROM AUTHOR]

[Display omitted] • Host factors and pathways were screened out in asthma and COVID-19 comorbidity. • Host factors of COVID-19 and asthma comorbidity involved in multiple pathways. • Networks of ACE2-related host factors in COVID-19 and asthma were revealed. • Estradiol and so on were identified as potential drugs for comorbidity treatment. ACE2 as a functional receptor for SARS coronavirus plays an important role in COVID-19 infection of the host. Thus, we aimed to explore interaction networks between ACE2 and common host factors in COVID-19/Asthma comorbidity. We identified 1,191 protein targets closely related to ACE2, and integrated the GEO database and multiple public databases to identify 305 host factors related to ACE2 between COVID-19/Asthma comorbidity. Further enrichment analyses showed that metabolic processes, Th1 and Th2 cell differentiation and PPAR signaling pathways had vital significance in the comorbidity of asthma and COIVD-19. HRAS, IFNG, CAT, CDH1, FASN, ACLY, CCL5, VCAM1, SCD and HMGCR were the key host factors related to ACE2. Tissue-specific enrichment and correlation analysis with ACE2 showed that SCD, CAT and FASN were highly expressed in the lung; and these 10 molecules were closely related to ACE2 and specifically expressed in multiple tissues. We also identified a series of drugs, such as estradiol, tetrachlorodibenzodioxin, resveratrol, cyclosporine, perfluorooctanoic acid and so on. Finally, the expression levels and diagnostic performance of HRAS and SCD showed statistical significance in external databases. This study explored the interaction networks of ACE2-related host factors in COVID-19 and asthma and identified several potential drugs for COVID-19/Asthma comorbidity. Although our research needs further verification, it still informs the mechanisms and treatment of COVID-19/Asthma comorbidity. [ABSTRACT FROM AUTHOR]

Background: Heart failure is a major health concern and often requires echocardiography to confirm the diagnosis. We introduce a new method that uses a wearable heart sound and electrocardiogram (ECG) device that can be used in the outpatient setting.Objective: The purpose of this study was to determine the value of synchronized analysis of heart sounds and ECG in identifying patients with depressed left ventricular ejection fraction (dLVEF) <50%.Methods: One hundred eighty-nine patients (76 with dLVEF; 113 with normal ejection fraction) were enrolled. All were admitted to the hospital because of dyspnea or chest discomfort. N-Terminal pro-B-type natriuretic peptide (NT-proBNP) was measured in all patients. LVEF was determined by echocardiography. Heart sound and ECG signals were simultaneously recorded using the wearable synchronized phonocardiogram and ECG device. Heart sound and ECG signals were automatically analyzed using wavelet analysis and utilized to determine electromechanical activation time (EMAT), EMAT/RR, S1-S2 time, and S1-S2/RR.Results: EMAT in the dLVEF group was significantly higher than that in the control group (159.82 ± 83 ms vs 91.58 ± 28 ms). Pearson correlation test showed a negative correlation between EMAT and LVEF (r = -0.449; P <.001). Receiver operating characteristic curve analysis demonstrated that the sensitivity and specificity of EMAT ≥104 ms for the diagnosis of EF <50% were 92.1% and 92%, respectively. Patients with intermediate NT-proBNP values were identified as dLVEF by EMAT ≥104 ms, with sensitivity of 93.5% and specificity of 92.8%.Conclusion: The heart sound and ECG signal index EMAT contributes to the diagnosis of EF <50% and is especially helpful in patients with an inconclusive NT-proBNP value. [ABSTRACT FROM AUTHOR]

The H (hypothalamic)-P (pituitary)-I (interrenal) axis is critical in the stress response and other activities of fish. To further investigate cadmium (Cd) toxicity on the H-P-I axis and to identify its potential regulatory genes in fish, the adult female rare minnows ( Gobiocypris rarus ) were exposed to subchronic (5 weeks) levels of waterborne Cd in the present study. This kind of treatment caused dose-dependent decline in fish growth, with significance in the high dose group (100 μg/L). Correspondingly, low dose (5–50 μg/L) waterborne Cd disrupted the endocrine system of H-P-I axis just at the secretion level, while high dose Cd disrupted both the secretion and synthesis of cortisol and its downstream signals in rare minnows, revealed by the significantly upregulation and positive correlation of corticosteroidogenic genes including MC2R , StAR , CYP11A1 , and CYP11B1 in the kidney (including the interrenal tissue) ( P < 0.05), and the significant alteration of Glcci1 , Hsp90AA and Hsp90AB in the hepatopancreas, gill and intestine as well ( P < 0.05). The expression of Glcci1 was significantly decreased in hepatopancreas, gill and intestine of tested fish following treatment, and its positive correlation with GR (Glucocorticoid receptor) suggested its potential regulation on the cortisol and/or H-P-I axis in fish. The expression of FKBP5 in the intestine was positively and significantly correlated with that of Hsp90AA ( P < 0.05), and the Hsp90AB transcript in the hepatopancreas was positively correlated with that of Hsp90AA ( P < 0.05), which indicated that Hsp90AA and Hsp90AB were more likely to serve as cofactors of GR and FKBP5 in response to Cd exposure. [ABSTRACT FROM AUTHOR]

• Rare minnows were exposed to waterborne cadmium. • Lipid metabolism was disrupted and the underlying mechanisms were investigated. • Large size lipid droplets (LD) and the appearance of nuclear LD in hepatocytes were detected after exposure to cadmium. • nLD and ectopic deposition of LD in Kupffer cells were reported in lower vertebrates for the first time. • Disruption of lipid transport might be involved in the hepatic accumulation of LD. Cadmium (Cd) is a widely distributed aquatic toxic heavy metal with the potential to disrupt fish metabolism; however, more research is needed to clarify the underlying mechanisms. In the present study, rare minnows (Gobiocypris rarus) were used to detect the effects of cadmium on freshwater fish lipid metabolism and its underlying mechanism by histopathological observation, measurement of serum and liver biochemical indexes, and analysis of gene expression in terms of lipid oxidation, synthesis and transport. Here, severe damage, such as cytoplasmic lipid droplet (LD) accumulation, ectopic deposition of LDs, and the appearance of nuclear LDs (nLDs), was detected after exposure to 2.0 mg/L or higher concentrations (2.5 and 2.8 mg/L CdCl 2) for 96 h. Other damage included abnormal increases in rough endoplasmic reticulum (RER) lamellae in a fingerprint or concentric circle pattern and necrosis of hepatocytes, and which was observed in the livers of fish exposed to 2.0 mg/L CdCl 2.. Both hepatic and serum lipids, such as triglycerides and total cholesterol, were significantly increased after exposure to 2.0 mg/L CdCl 2 , as was serum lipase (LPS). Hepatic lipase and lipoprotein lipase remained unchanged, in accordance with the unchanged hepatic mRNA transcripts of PPARɑ. Furthermore, the mRNA transcripts of both SCD and SQLE were significantly decreased. Moreover, hepatic and serum low-density and high-density lipoprotein cholesterol showed significant changes, which were accompanied by a significant increase and decrease in hepatic APOAI and APOB100 mRNA levels, respectively. All the results indicate the presence of severe damage to hepatic lipid metabolism and that disrupted lipid transport may play a key role in the accumulation of hepatic LDs. In addition, the hepatic nLDs of nonmammalian vertebrates and their location across the nuclear envelope are intriguing, suggesting that large-size nLDs are a common marker for severe liver damage. [ABSTRACT FROM AUTHOR]

Rare minnow ( Gobiocypris rarus ) is a widely used experimental fish in risk assessments of aquatic pollutants in China. Cadmium (Cd) is one of the most toxic heavy metals in the world; however, few studies have used fish gills, a multi-functional organ. In this study, we characterized the differential expression of adult female rare minnow gills after sub-chronic waterborne Cd (75 μg/L CdCl 2 ) exposure for 35 d. A total of 452 genes (209 up-regulated and 243 down-regulated) were identified by gene expression profiling using RNA-Seq before and after treatment. Of these differentially expressed genes, 75, 21, and 54 differentially expressed genes are related to ion transport, oxidation-reduction processes, and the immune response, respectively. The results of GO and KEGG enrichment analyses, together with the altered transcript levels of major histocompatibility complex (MHC) class I and class II molecules and the significant increases in the levels of serum tumor necrosis factor α (TNF-α), interleukin 1β (IL1β) and nuclear factor-κB (NF-κB), indicated a disruption of the immune system, particularly the induction of inflammation and autoimmunity. The significant down-regulation of coagulation factor XIII A1 polypeptide (F13A1), tripartite motif-containing protein 21 (TRIM21), and Golgi-associated plant pathogenesis-related protein (GAPr) during both acute (≤ 96 h) and sub-chronic (35 d) waterborne Cd exposure, as well as their dosage dependence, suggested that these three genes could be used as sensitive biomarkers for aquatic Cd risk assessment. [ABSTRACT FROM AUTHOR]

The H (hypothalamic)–P (pituitary)–I (interrenal) axis plays a critical role in the fish stress response and is regulated by several factors. Cadmium (Cd) is one of the most toxic heavy metals in the world, but its effects on the H–P–I axis of teleosts are largely unknown. Using rare minnow ( Gobiocypris rarus ) as an experimental animal, we found that Cd only disrupted the secretion and synthesis of cortisol. Neither hormones at the H or P level nor the expressions of their receptor genes (corticotropin-releasing hormone receptor ( CRHR ) and melanocortin receptor 2 ( MC 2 R )) were affected. Steroidogenic acute regulator ( StAR ), CYP11A1 and CYP11B1 , which encode the key enzymes in the cortisol synthesis pathway, were significantly up-regulated in the kidney (including the head kidney). The level of 11β-HSD2 , which is required for the conversion of cortisol to cortisone, was increased in the kidney, intestine, brain, and hepatopancreas, whereas the expression of 11β-HSD1 , which encodes the reverse conversion enzyme, was increased in the gill, kidney and almost unchanged in other tissues. The enzyme activity concentration of 11β-HSD2 was increased in the kidney as well. The level of glucocorticoid receptor ( GR ) decreased in the intestine, gill and muscle, and the key GR regulator FK506 binding protein5 ( FKBP5 ) was up-regulated in the GR-decreased tissues, whereas the level of nuclear receptor co-repressor 1 ( NCoR1 ), another GR regulator remained almost unchanged. Thus, GR , FKBP5 and 11 β-HSD2 may be involved in Cd-induced cortisol disruption. [ABSTRACT FROM AUTHOR]

Arsenic, a common highly-toxic pollutant, is mainly associated with the hydrous ferric oxides in soils and minerals. A possible mechanism for arsenic mobilization is the reductive dissolution of iron (hydr) oxides. In this paper, the possibilities of iron-reducing bacteria Shewanella oneidensis MR-1 and Shewanella sp. strain MR-4 in mobilization, oxidization and methylation of arsenic were investigated. Under laboratory conditions, the dynamics of As- and Fe-release from arsenopyrite and scorodite under microbial activities, the transformation of arsenic release from iron minerals and the environment factors affecting the arsenic release and transformation during reactions were examined. The aqueous concentrations of different forms of As were determined by a liquid chromatography–atomic fluorescence spectrometry (LC–AFS) and the new surface morphology of iron minerals was also measured and characterized using scanning electron microscopy (SEM) and X-ray diffractometry (XRD). Results indicated that As could be dissolved from arsenopyrite or scorodite and oxidized or even methylated quickly in the presence of Shewanella strains. The transformation of arsenic forms were affected by the culture temperatures, pH of environment medium, and spiked Fe(III) content in the solutions. Moreover, solid-phase analysis revealed that the morphology and mineralogy in the solid-phase products were changed, such as many wrinkle-shaped gullies were formed on surfaces of iron minerals. The amount of secondary precipitates also increased with time. The As mobility could be enhanced by the activity of dissimilatory iron-reducing bacteria in the environment. This study provides insights into in situ remediation of As pollution. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mothers raising a child with ASD reported various levels of growth, mostly in the domain of personal strength. [•] Having another child may facilitate mothers’ growth in “appreciation of life” and mothers raising a boy with ASD experienced less “spiritual change” than those raising a girl. Length of diagnosis was not related to the growth. [•] Mothers’ growth could be promoted by increasing their deliberate rumination, reducing intrusive rumination, and increasing positive coping strategies after receiving their children's diagnosis of ASD. [Copyright &y& Elsevier]

Highlights: [•] HBO reduced long-term HI-induced behavior and histological impairment. [•] Improvements in behavioral outcomes were associated with morphological recovery. [•] HBO might exert protective effects by reducing caspase-3 and AIF-mediated apoptosis. [Copyright &y& Elsevier]

Abstract: Magnaporthe oryzae has been used as a model fungal pathogen to study the molecular basis of plant–fungus interactions due to its economic and genetic importance. In this study, we identified a novel gene, Moplaa, which is the homologue of Homo sapiens PLAA encoding a phospholipase A2-activating protein. Moplaa is conserved in some eukaryotic organisms by multiple alignment analysis. The function of the Moplaa gene was studied using the gene target replacement method. The Moplaa deletion mutant exhibited retarded growth and conidial germination, reduced conidiation, appressorial turgor pressure and pathogenicity to rice CO-39. Reintroduction of the gene restored defects of the Moplaa deletion mutant. [Copyright &y& Elsevier]

Abstract: Autophagy is a highly conserved process in lower to higher eukaryotic organisms, and occurs in many types of cells as tissues are remodeled during development. In this study, we investigated the functional role of the Trichoderma reesei TrATG5 gene, which encodes an essential protein required for autophagy. TrATG5 is conserved in structure and function in the filamentous fungi and might clearly rescue the pathogenicity function of MgATG5 in Magnaporthe oryzae. Target gene disruption was used to study the functions of TrATG5. It was found that the autophagic process was blocked in the TrATG5 deletion mutant. The mutant was sensitive to nutrient starvation, with abnormal conidiophores and reduced production of conidia. This new evidence might help to elucidate the molecular machinery of autophagy in filamentous fungi. [Copyright &y& Elsevier]

Summary: Ca2+ is a second messenger in pathways that transduce external signals and activate cellular processes in plants and animals. Ca2+-mediated signal transduction is involved in key pathways that contribute to a variety of fundamental physiological processes in eukaryotic cells. However, little is known about the molecular mechanisms of Ca2+-mediated signal transduction in filamentous fungi. In this study, the MoCMK1 gene, encoding a putative Ca2+/calmodulin-dependent kinase, was identified in the rice blast fungus Magnaporthe oryzae. Three MoCMK1 deletion mutants were obtained by a targeted gene replacement. Colonies of the MoCMK1 mutants had sparse aerial hyphae and fewer conidia than the wild-type strain on complete medium. Conidial germination and appressorial formation were delayed in the ΔMocmk1 mutants. In spray inoculation tests, ΔMocmk1 mutants exhibited a weakened ability to infect the susceptible rice cultivar CO-39, compared to the wild-type strain Guy11. These results showed that MoCMK1 plays key roles in the pathogenicity of the rice blast fungus. [Copyright &y& Elsevier]

Abstract: In this paper, we consider an inverse problem of heat equation with Robin boundary condition for identifying heat transfer coefficient. Combining the method of fundamental solutions with discrepancy principle for the choice of the locations for source points, we give a method for solving the reconstruction problem. Since the resultant matrix is severe ill-conditioning, Tikhonov regularization with L-curve method is employed. Some numerical examples are given for verifying the efficiency and accuracy of the presented method. [Copyright &y& Elsevier]

Abstract: Thyroid cancer is the most common endocrine malignancy and exhibits the full range of malignant behaviors from the relatively indolent occult differentiated thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer. Iodine is a well known key element in thyroid normal function maintenance and thyroid cancer development. However, the effects induced by iodine and the molecular mechanisms involved remain poorly understood in thyroid cancer. We investigated the apoptotic effect of iodine on three different subtypes of thyroid cancer cells. We observed that apoptosis induced by iodine was mitochondrial-mediated. Iodine treatment decreased the level of mutant p53 including the R273H mutant that possesses anti-apoptotic features, but increased the p21 level. Surprisingly, high doses of iodine promoted instead of suppressed the expression of anti-apoptotic protein Bcl-xL expression. Moreover, iodine transiently activated the subfamily members of mitogen activated protein kinases (MAPKs) (ERK1/2, p38 and JNK1/2) which contribute to modulate p53, p21 and Bcl-xL expression. The further results showed the three subfamily members of MAPKs all worked as anti-apoptotic factors. Collectively, iodine-induced apoptotic pathway is involved in the activation of MAPKs-related p21, Bcl-xL and mutant p53 regulation. The findings provide solid molecular evidence to explain the potential pathway for iodine to influence thyroid cancer development. It may also reveal some novel molecular targets for the treatment of thyroid cancer. [Copyright &y& Elsevier]

Abstract: Autophagy is a ubiquitous degradative pathway for the bulk degradation of eukaryotic macromolecules and organelles in eukaryotic cells (Klionsky, 2005; Levine and Klionsky, 2004). Previously, the role of autophagy in turgor generation in plant pathogenic fungi was unknown. Currently, autophagy is confirmed as an important pathway for turgor accumulation in the appressorium (the tips of the invasive hyphae; Liu et al., 2007b) using a technique of targeted gene replacement, deleting the genes that code for Magnaporthe oryzae homologs of yeast autophagy‐related (ATG) genes ATG2, ATG4, ATG5, ATG8, ATG9, and ATG18 (Liu et al., 2007a). All of these null mutants fail to breach the cuticle of the host. This chapter will first look at some methodologies to analyze the functions of autophagy‐related gene products at the biological, cellular, and molecular level in this model plant pathogenic fungi, and then provide some research evidence of the role of autophagy in the promotion of the formation of the infection structure and pathogenicity to point out some significant areas for further research in this field. [Copyright &y& Elsevier]

Objective: Accumulated evidence suggests that myogenesis and angiogenesis induced by implanted cells play important roles in restoring cardiac function after a myocardial infarction. The current study investigated the effects of transplanted autologous mesenchymal stem cells overexpressing angiogenin on myocardial perfusion and cardiac function in the porcine chronic ischemic model. Methods: Chronic ischemia was generated in Yorkshire pigs by placing an ameroid constrictor around the left circumflex artery. Four weeks after occlusion, the animals were randomly separated into 4 groups: pigs in the MSCAdAng or MSCAdNull groups were implanted with 6 × 108 mesenchymal stem cells infected with adenovirus containing angiogenin gene or null adenovirus, respectively; pigs in the AdAng or AdNull groups were injected intramyocardially with adenovirus (5 × 109 plaque forming unit/pig) containing angiogenin gene or null adenovirus, respectively. Four weeks after implantation, mesenchymal stem cells prelabeled with DiI were observed within the implanted area in both cell transplantation groups. Results: Angiogenin protein levels were significantly greater in the MSCAdAng and AdAng groups than in the other 2 groups and were associated with greater neovessel formation than in the other 2 groups. Mesenchymal stem cell transplantation decreased scar size and increased scar thickness. Both the AdAng and MSCAdNull groups experienced improved cardiac function compared with that seen in the AdNull group. However, a synergistic effect of mesenchymal stem cells and angiogenin was observed in the MSCAdAng group because myocardial perfusion and cardiac function increased significantly (P < .05 for all groups) in this group compared with all the others. Conclusions: Transplantation of autologous mesenchymal stem cells transfected with the angiogenin gene revealed a synergistic effect on the improvement of heart perfusion and function after ameroid occlusion. [Copyright &y& Elsevier]

Abstract: Molecular dynamics simulations were performed on modeled kinase–substrate complexes in an attempt to establish a relationship between structural features and binding ability of the complexes. We found that the monitored distance between substrate nucleophilic oxygen (OG) and attacked phosphorus (PG) of ATP analog correlated closely with the binding affinity. With reference to 3.3Å, the van der Waals sum of oxygen and phosphorus, the calculated distances of good substrates were close to it whereas those of poor substrates were far apart from it. Therefore, it is reasonable to consider the OG–PG distance as a potential criterion to prefigure the kinase–substrate binding specificity and the simple computational techniques may work as an easy approach to distinguish good substrates from weak or poor substrates. [Copyright &y& Elsevier]

Abstract: Introduction: Spinal teratomas are extremely rare; they constitute <0.5% of all spinal cord tumors. These rare tumors have nonspecific manifestations but in most cases are accompanied by neurological deficits. Rupture of a mature teratoma can cause chemical meningitis. Patient Description: A 7-year-old boy presented with paroxysmal abdominal pain and a history of recurrent aseptic meningitis. Kernig and Brudzinski signs were present. Lumber puncture revealed pleocytosis with no evidence of bacteria growth. Imaging of the spine revealed a cystic lesion in spinal cord at thoracic level 9-11. Endoscopic excision of the cyst was successfully performed. Surgical and histopathological findings confirmed extramedullary matured teratoma. Conclusions: As the symptomatic attacks of spontaneous rupture of spinal teratoma resemble presentations of Mollaret meningitis, spinal teratoma should be considered in the differential diagnosis of Mollaret meningitis. We describe a rare example of spinal teratoma causing recurrent meningitis. Spine imaging should be considered in individuals with recurrent aseptic meningitis as this promotes earlier diagnosis, more appropriate treatment, and improved neurological outcome. [Copyright &y& Elsevier]

Abstract: Vascular wall chronic inflammation plays a critical role in the development and progression of cardiovascular diseases such as atherosclerosis and hypertension. Circulating and tissue angiotensin II can induce potent inflammatory responses in vascular cells and promotes atherosclerosis, whereas the underlying mechanisms remain uncertain. Several data indicated that the upregulation of Th17 response has been found in the local atherosclerotic lesions and circulating lymphocytes in atherosclerosis prone models and the onset of acute coronary syndrome. Evidence from animal models shown that angiotensin II not only induced the Th1 response, but also amplified Th17 response. In addition, angiotensin II-induced hypertension and vascular dysfunction were abolished by blocking Th17/IL-17 effects. Therefore, we hypothesized that Th17 response may play an important role in angiotensin II-induced atherosclerosis. [Copyright &y& Elsevier]

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB. [ABSTRACT FROM AUTHOR]

Objectives Chinese people are generally unfamiliar with the concept of advance care planning or advance directives (ACP/ADs), which raises dilemmas in life-support choice and can even affect clinical decision making. To understand and address the issues involved better, we investigated the awareness of ACP/ADs in China, as well as people's attitudes toward medical autonomy and end-of-life care. Design A multicenter cross-sectional survey, conducted from August 1 to December 31, 2016. Setting Twenty-five hospitals located in 15 different provinces throughout mainland China. Participants Pairs of adult patients without dementia or malignancies, and a family member. Measurements Participants self-filled anonymous questionnaires, and the data collected were analyzed to relate patients' sociodemographic characteristics to their awareness of ACP/ADs and attitudes to health care autonomy and end-of-life care. Results Among 1084 patients who completed the questionnaire, 415 (38.3%) had heard about ACP/ADs. Having been informed about ACP/ADs, 995 (91.8%) were willing to find out their true health status and decide for themselves; 549 (50.6%) wanted to institute ACP/ADs. Regarding end-of-life care, 473 (43.6%) chose Do Not Resuscitate, and 435 (40.1%) wished to forgo life-support treatment if irreversibly moribund. Patients predominantly (481, 44.4%) chose general hospital as their preferred place to spend their last days of life; only 114 (10.5%) favored a special hospice facility. Patients' main concerns during end-of-life care were symptom control (35.1%), followed by functional maintenance and quality of life (29.8%), and prolonging life (18.9%). More highly educated patients had significantly greater awareness of ACP/ADs than less well educated ones (χ 2 = 59.22, P < .001) and were more willing to find out the truth for themselves (χ 2 = 58.30, P ≤ .001) and make medical decisions in advance (χ 2 = 55.92, P < .001). Younger patients were also more willing than older ones to know the truth (χ 2 = 38.23, P = .001) and make medical decisions in advance (χ 2 = 18.42, P = .018), and were also more likely to wish to die at home (χ 2 = 96.25, P < .001). Only 212 patients’ family members (19.6%) wanted life-support treatment for themselves if irreversibly moribund, whereas 592 (54.6%) would want their relative to receive such procedures in the same circumstances; a similar discrepancy was evident for end-of-life invasive treatment (18.3% vs 42.7%). Conclusions Awareness about ACP/ADs in China is still low. Providing culturally sensitive knowledge, education, and communication regarding ACP/ADs is a feasible first step to promoting this sociomedical practice. [ABSTRACT FROM AUTHOR]

• The local flexibility matrix of the inclined cracked functionally graded material (FGM) beam is studied and validated. • The bending and tensile stiffnesses of the inclined cracks and their interaction are taken into consideration. • The vibrations of the FGM beam with multiple inclined cracks are investigated. • The wave propagation characteristics of the cracked FGM beam are presented. This paper proposes an FEA method to study the vibration and wave propagation in functionally graded material (FGM) beams with multiple inclined cracks by introducing the local flexibility matrix caused by the cracks. The bending and tensile stiffnesses of the inclined cracks and their interaction are taken into consideration. Two-node (three degrees of freedom per node) beam element is used. The inclined cracks are equivalent to transversal cracks to calculate the additional flexibility matrix of the inclined cracked FGM beam element. The material properties of the FGM beam are supposed to satisfy the exponential law along its thickness. The governing equations of motion for the FGM beam with multiple inclined cracks are deduced in the frame of Euler-Bernoulli theory and Lagrange function, and numerically solved by the Newmark average acceleration method. Both theoretical and numerical comparisons are presented to validate the present method for the inclined cracked FGM beam with varying boundary conditions, arbitrary inclined crack angles as well as varying inclined crack lengths. The effects of the location, length, inclined angle and number of the inclined cracks as well as material property ratio on the fundamental frequencies and wave propagation characteristics of the inclined cracked cantilever FGM beams are comprehensively investigated. [ABSTRACT FROM AUTHOR]

The endophytic fungus Harpophora oryzae is a beneficial endosymbiont isolated from wild rice. H. oryzae can not only promote rice growth and biomass accumulation but also protect rice roots from invasion by its close relative Magnaporthe oryzae . Autophagy is a highly evolutionary conserved process from lower to higher eukaryotic organisms, and is involved in the maintenance of normal cell differentiation and development. In this study, we isolated a gene ( HoATG5 ) which encodes an essential protein required for autophagy from the beneficial endophyte fungus H. oryzae . Using targeted gene replacement, a ΔHoATG5 mutant was generated and used to investigate the biological functions of autophagy in H. oryzae . We found that the autophagic process was blocked in the HoATG5 deletion mutant. The mutant showed increased vegetative growth and sporulation, and was sensitive to nutrient starvation. The ΔHoATG5 mutant lost its ability to penetrate and infect the wounded barley leaves. These results provide new knowledge to elaborate the molecular machinery of autophagy in endophytic fungi. [ABSTRACT FROM AUTHOR]

In this paper we propose a novel fuzzy hybrid quantum artificial immune clustering algorithm based on cloud model (C-FHQAI) to solve the stochastic problem. Fuzzy hybrid quantum artificial immune algorithm can be developed with some of the advantages of information processing where there is a certain amount of indeterminism with qubits, i.e. quantum bits, replacing classical neurons having deterministic states and also in place of the classical artificial immune algorithm with quantum operators. The fuzzy combinatorial fuzzy hybrid quantum artificial immune clustering algorithm (C-FHQAI) is more expressive than the other fuzzy theories and methods. Finally, numerical examples show that the clustering effectiveness of the C-FHQAI algorithm is fast convergence and improves the accuracy of the fuzzy calculation. We find that the C-FHQAI clustering algorithm has the perspective of widespread application. [ABSTRACT FROM AUTHOR]

Abstract: Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions. The term autophagy denotes any cellular process which involves the delivery of cytoplasmic material to the lysosome for degradation. Autophagy, in filamentous fungi plays a critical role during cellular development and pathogenicity. Autophagy, like the mitogen-activated protein (MAP) kinase cascade and nutrient-sensing cyclic AMP (cAMP) pathway, is also an important process for appressorium turgor accumulation in order to penetrate the leaf surface of host plant and destroy the plant defense. Yeast, an autophagy model, has been used to compare the multi-valued functions of ATG (autophagy-related genes) in different filamentous fungi. The autophagy machinery in both yeast and filamentous fungi is controlled by Tor kinase and both contain two distinct phosphatidylinositol 3-kinase complexes. In this review, we focus on the functions of ATG genes during pathogenic development in filamentous fungi. [Copyright &y& Elsevier]

Abstract: Angiogenin, a basic heparin-binding protein, has been shown to play a key role in tumor growth and angiogenesis. It was found in the present study that 67 out of 100 lung adenocarcinomas exhibited angiogenin nuclear expression, and this nuclear expression correlated with vascular and pleural invasion as well as positive lymph node metastasis. To down-regulate angiogenin expression, we constructed an adenoviral-vector based short hairpin RNA system. ELISA, real-time qPCR and immunocytochemical staining demonstrated that adenoviral-vector based siRNA decreased angiogenin mRNA level and protein secretion, and inhibited angiogenin nuclear expression in A549 cells, resulting in marked inhibition on ribosomal RNA transcription, in vitro cell proliferation, soft agar colony formation, and xenograft tumor proliferation and angiogenesis. Experiments with neomycin further confirmed that angiogenin nuclear expression played an important role in tumor growth. Based on these data, we concluded that angiogenin nuclear expression played a dual role in the growth of lung adenocarcinoma with respect to cancer cell proliferation and angiogenesis. [Copyright &y& Elsevier]

Three Zn(II)-CPs were synthesized and used as photocatalyst for dye degradation. [Display omitted] Three newly developed coordination polymers (CPs), denoted as [Zn 2 (HL)(ptp) 2 ] n (1) , [Zn(HL)(bpz)·0.25H 2 O] n (2) and [Zn(HL)(bic)·H 2 O] n (3) , have been synthesized using hydrothermal methods. These CPs are composed of zinc ions and specific ligands with 3-(4-carboxyphenoxy)-5-methylbenzoic acid (H 3 L); 3,5-bis(4-pyridyl)-1,2,4-triazolyl (ptp); 3,3ʹ,5,5ʹ-tetramethyl-4,4ʹ-bipyrazole (bpz) and 3,6-bis(imidazol-1-yl)-9H-carbazole (bic) which provide oxygen and nitrogen donor sites. The molecular structures of the CPs were determined through single X-ray diffraction analysis, revealing a tetrahedral geometry. The CPs 1 – 3 have distorted tetrahedral geometry. The layered structural progression, starting from the tetrahedral complex and moving towards 1D, 2D, and potentially 3D networks, showcases the intricacies and hierarchical nature of CP 1 – 3 's molecular architecture. An interesting property of these CPs is their semiconducting nature. They exhibit the ability to serve as photocatalysts, especially against organic pollutants such as Acid chrome blue (ACB), Methyl blue (MB), Methyl orange (MO), and Rhodamine B (RhB). Among the CPs, CP 1 demonstrates superior photocatalytic activity against RhB (RhB) at a concentration of 25 mg/L. This suggests that CP 1 , when used in a quantity of 25 mg, exhibits enhanced efficiency in degrading RhB through photocatalysis. The optimal conditions, where 25 mg/L RhB and 25 mg of CP 1 are employed, result in the degradation of an impressive 97.51 % of RhB. [ABSTRACT FROM AUTHOR]

Three Zn(II)-CPs were synthesized and used as photocatalyst for dye degradation. [Display omitted] Three novel Zn(II)-based CPs (coordination polymers) with formula [Zn 3 (μ 3 -OH)(L)(H 2 O) 5 ] n (1), [Zn 5 (L) 2 (bpz) 2 (H 2 O) 2 ] n (2) and [Zn 2 (HL)(bip)(H 2 O) 2 ·H 2 O] n (3) (H 5 L = 3,5-di(2ʹ,4ʹ -dicarboxyphenyl)benozoicacid, bpz = 3,3ʹ,5,5ʹ-tetramethyl-4,4ʹ-bipyrazole and bip = 3,5-bis(1-imidazoly)pyridine have been synthesized hydrothermally by O and N donor ligands. The single x-ray diffraction reveals that CPs are mixed geometry. In CP 1 , Zn1 is square pyramidal geometry and Zn3 is distorted octahedral. In CP 2 , Zn1 is tetrahedral; Zn2 is distorted octahedral and Zn3 is square pyramid geometry. In CP 3 , Zn metals are distorted octahedral. By interacting with intra- and intermolecular hydrogen bonds, all CPs are stable. The nature of these CPs is semiconducting. Methyl blue (MB), Methyl orange (MO), Methyl violet (MV), and Rhodamine B (RhB) are examples of organic pollutants against which the photocatalytic activity of CPs is studied. CP 3 (25 mg) have higher photocatalytic activity against MV (20 ppm) under pH 6 condition. [ABSTRACT FROM AUTHOR]

We investigated the in vivo toxicity of InP/ZnS quantum dots (QDs) in Chinese rare minnow ( Gobiocypris rarus ) embryos. The 72 h post-fertilization (hpf) LC 50 (median lethal concentration) was 1678.007 nmol/L. Rare minnows exposed to InP/ZnS QDs exhibited decreased spontaneous movement, decreased survival and hatchability rates, and an increased malformation rate. Pericardial edema, spinal curvature, bent tails and vitelline cysts were observed. Embryonic Wnt8a and Mstn mRNA levels were significantly up-regulated after InP/ZnS QDs treatment at 48 hpf (200 nmol/L) (p < 0.05). The superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels at 96 hpf (800 nmol/L) had an increasing trend. Hsp70 mRNA expression was significantly changed at 48 hpf (200 nmol/L), but compared with the blank control, the different InP/ZnS QDs treatments did not significantly change the Olive tail moments (p > 0.05). Thus, InP/ZnS QDs caused teratogenic effects and death during the development of Chinese rare minnow embryos, but InP/ZnS QDs did not cause significant genetic toxicity during Chinese rare minnow development. [ABSTRACT FROM AUTHOR]

Triphenyltin (TPhT) is a kind of organotin compounds which have been used ubiquitously as herbicide, pesticide, and fungicide in agriculture. The present study provides the possibility to detect and monitor TPhT with normal Raman spectroscopy and surface enhanced Raman scattering (SERS) spectroscopy. Firstly, the complete vibrational Raman spectra characterization of TPhT along with the IR spectroscopy were reported for the first time. Then a wide range of pH values were carried out to choose the optimal pH value in TPhT detection by using Raman spectroscopy. Afterwards, Raman spectra of various TPhT solutions were collected and analyzed. The results indicate that the optimal pH value for TPhT detection by Raman spectroscopy is 5.5, and with silver nanoparticles (Ag NPs) as SERS substrate is an effective technique for trace TPhT detection with an enhancement by 5 orders of magnitude and the detection limit can be as low as 0.6 ng/L within less than 30 s. Finally, in this study, the residual of TPhT on apple peel was investigated by casting different concentrations of TPhT on apple peel under the current optimized condition. The result demonstrates that TPhT could be detected based on its SESR spectra at 6.25 ng/cm 2 in standard solutions. [ABSTRACT FROM AUTHOR]

Magnaporthe oryzae infects rice, wheat and other grass crops through appressoria. The formation of the appressorium is regulated by the external environment, signal transduction pathways, and transcription factors. Transcription factors Vrf1 and Hox7 are involved in the regulation of appressorium formation. In this study, we demonstrate that Vrf1 and Hox7 play vital roles in coordinately regulating appressorium maturation. In strain 70–15, deletion of VRF1 resulted in the inability to continue melanization and maturation of the incipient appressorium, and deletion of HOX7 also resulted in defects in appressorium melanization and maturation. The defects in appressorium formation in Δ hox7 Δ vrf1 were similar to those in Δ hox7 and Δ vrf1. The gene expression profiles of the incipient appressoria at 5 h post-inoculation (hpi) showed that the expression levels of 704 genes (25.94 % of all differentially expressed genes in the three mutants) were significantly downregulated (606 genes) or upregulated (98 genes). In the appressoria of Δ hox7 , Δ vrf1 , and Δ hox7 Δ vrf1 at 5 hpi, the expression level of genes related to cell wall remodeling was changed. Genes for melanin synthesis, chitin and glucan degradation, and extracellular cell wall degrading enzyme were significantly downregulated, while genes for chitin and glucan synthesis were upregulated. After 8 hpi, the incipient appressoria of Δ hox7 , Δ vrf1 , and Δ hox7 Δ vrf1 regerminated and formed swollen hyphal-like structures with multiple nuclei. The ratio of the nuclear number of the hyphal-like structures of Δ hox7 , Δ hox7 Δ vrf1 , and Δ vrf1 was close to 6:4:2 at 24 hpi. Therefore, although Vrf1 and Hox7 are somewhat functionally different, they synergistically regulate appressorium maturation in M. oryzae. [ABSTRACT FROM AUTHOR]

The endophytic filamentous fungus Harpophora oryzae is a beneficial endosymbiont isolated from the wild rice. H. oryzae could not only effectively improve growth rate and biomass yield of rice crops, but also induce systemic resistance against the rice blast fungus, Magnaporthe oryzae . In this study, Agrobacterium tumefaciens -mediated transformation (ATMT) was employed and optimized to modify the H. oryzae genes by either random DNA fragment integration or targeted gene replacement. Our results showed that co-cultivation of H. oryzae conidia with A. tumefaciens in the presence of acetosyringone for 48 h at 22 °C could lead to a relatively highest frequency of transformation, and 200 μM acetosyringone (AS) pre-cultivation of A. tumefaciens is also suggested. ATMT-mediated knockout mutagenesis was accomplished with the gene-deletion cassettes using a yeast homologous recombination method with a yeast– Escherichia – Agrobacterium shuttle vector pKOHo. Using the ATMT-mediated knockout mutagenesis, we successfully deleted three genes of H. oryzae ( HoATG5 , HoATG7 , and HoATG8 ), and then got the null mutants Δ Hoatg5 , Δ Hoatg7 , and Δ Hoatg8 . These results suggest that ATMT is an efficient tool for gene modification including randomly insertional mutagenesis and gene deletion mutagenesis in H. oryzae. [ABSTRACT FROM AUTHOR]

Calpains are intracellular, cysteine proteases found in plants, animals and fungi functioning as signal transduction components in different cellular pathways including sporulation and alkaline adaptation in fungi. Calpains-related MoCAPN1 (MGG_14872), MoCAPN3 (MGG_15810) and MoCAPN4 (MGG_04818) genes from Magnaporthe oryzae genome which are 2604, 3513 and 771-bp in length and encoding identical proteins of 867, 1170 and 256 amino acids were functionally characterized for different phenotypes through gene disruption method. All the mutants except those for MoCAPN1 showed normal phenotypes. In pathogenicity test, the mutants did not lead to any visible changes in phenotypes causing similar blast lesions on blast susceptible rice and barley leaves as those of the Guy-11 strain suggesting no major role in pathogenicity. Germ tubes formation, appressorium formation, mycelium radial growth and mating with 2539 strain were indistinguishable among the mutants and Guy-11 strains. Cell wall integrity (congo red) test, stress response under chemical pressure (ZnSO 4 , CuSO 4 and CdCl 2 ), osmotic and oxidative (NaCl and H 2 O 2 ) stress response, growth response on glucose and nitrogen deficient media resulted in similar results in the mutants and Guy-11 strains. However, mutants for Δ MoCAPN1 gene produced reduced (0.57 ± 0.15B and 0.54 ± 0.05B) conidia compared to that (1.69 ± 0.13A) of the Guy-11 strain showing its involvement in conidiation. [ABSTRACT FROM AUTHOR]

The fretting corrosion behavior of quench–polish–quench (QPQ)-treated TP316H steel was investigated in liquid sodium at 450 °C. The surface of the sample after QPQ is a multi-layer structure, consisting of the outermost oxide layer, the middle nitriding layer, and an underneath diffusion layer. The fretting wear and corrosion increased the material damage. With increasing thickness of the nitriding layer, the cross-sectional hardness and wear resistance remarkably increased, the fretting corrosion volume decreased. The effect of multilayer structure anti-wear and anti-corrosion were examined. Possible fretting corrosion mechanisms of the multilayer structure prepared by QPQ on TP316H in liquid sodium are discussed. • Time of QPQ treatments influence the multilayer structure of modified surface. • The high-hardness nitriding layer exerts the main anti-wear effect. • The diffusion layer exerts better anti-corrosion effect, and decomposes into the harder CrN and α-Fe phases. • QPQ treatments are promising for combating fretting corrosion of TP316H in liquid sodium. [ABSTRACT FROM AUTHOR]

Pyrolysis of Spartina alterniflora (smooth cordgrass) was investigated by thermogravimetric analysis in a nitrogen atmosphere at heating rates of 5, 10, 20, and 40 °C/min. Main weight-loss was observed in smooth cordgrass at temperatures ranging from 200 °C to 360 °C, owing to release of 72%–74% of total volatiles. Pyrolysis characteristics such as distribution of pyrolysis products and thermal-decomposition rate significantly changed based on heating rate, but had no significant effect on the total yield of volatile matters. Activation energy was evaluated by four model-free methods, namely, Friedman, Flynn–Wall–Ozawa (FWO), Kissinger–Akahira–Sunose (KAS), and Kissinger methods. Experimental results showed that the activation energy obtained from the Kissinger method was in agreement with the average value of activation energy (183.6 kJ/mol to 183.4 kJ/mol) determined by FWO and KAS methods. Results of the master-plots method indicated that the most probable reaction model function was f (a) = (1 − a)3.37 under activation energy of 183.5 kJ/mol. [ABSTRACT FROM AUTHOR]

Abstract: Over-expression of cleaved cyclin E in breast tumors is closely associated with tumor progression and resistance to antiestrogens. 17β-Estradiol (E2) has been recently shown to induce cyclin E processing in breast cancer cells. Tamoxifen has been used in patients with estrogen-sensitive breast cancer, yet resistance to antiestrogens and recurrence will appear in some of the patients after its continued use. We therefore addressed possible effects of tamoxifen on the generation of cleaved cyclin E and its signal mechanism(s) in estrogen-responsive MCF-7 breast cancer cells that express both G protein-coupled protein (GPR) 30 and estrogen receptor α (ERα). 4-Hydroxytamoxifen (OHT, tamoxifen's active form) failed to prevent E2-induced proteolysis of cyclin E and migration, but rather triggered cyclin E cleavage coincident with augmented migration. OHT-induced cyclin E truncation also occurred in SK-BR-3 cells that express GPR30 and lack ERα, but not in MDA-MB-231 cells that express neither GPR30 nor ERα. G1, a specific GPR 30 agonist, caused dramatic proteolysis of cyclin E and enhanced migration. Furthermore, OHT-stimulated cleavage of cyclin E and migration were tremendously attenuated by G15, a GPR30 antagonist, or siRNA against GPR30. In addition, inhibitors for EGFR or ERK1/2 remarkably suppressed OHT-induced truncation of cyclin E, suggesting involvement of EGFR signaling. Collectively, our data indicate that OHT contributes to the production of proteolyzed cyclin E via GPR30 with augmented migration in MCF-7 cells. [Copyright &y& Elsevier]

Abstract: Mon1 protein is involved in cytoplasm-to-vacuole trafficking, vacuolar morphology and autophagy, and is required for homotypic vacuole fusion in Saccharomyces cerevisiae. Here we identify MoMON1 from Magnaporthe oryzae as an ortholog of S. cerevisiae MON1, essential for the morphology of the vacuole and vesicle fusion. Target gene deletion of MoMON1 resulted in accumulation of small punctuate vacuoles in the hypha and hypersensitivity to monensin, an antibiotic that blocks intracellular protein transport. The ΔMomon1 mutant exhibited significantly reduced aerial hyphal development and poor conidiation. Conidia of ΔMomon1 were able to differentiate appressoria. However, ΔMomon1 was non-pathogenic on rice leaves, even after wound inoculation. In addition, ΔMomon1 was slightly hypersensitive to Congo red and SDS, but not to cell wall degrading enzymes, suggesting significant alterations in its cell wall. The autophagy process was blocked in the ΔMomon1 mutant. Taken together, our results suggest that MoMON1 has an essential function in vacuolar assembly, autophagy, fungal development and pathogenicity in M. oryzae. [Copyright &y& Elsevier]

Abstract: Aims: To explore the effect and mechanism of exendin-4 on dexamethasone-induced apoptosis in pancreatic β-cells. Methods: Murine MIN6 pancreatic β-cells were treated with dexamethasone (100nmol/l) over 48h following pretreatment with exendin-4 (100nmol/l). Cell viability was determined using an MTT assay. The percentage of apoptotic cells was determined through fluorescence microscopy analysis after Hochest/PI staining and a flow cytometric assay after Annexin V-FITC/PI staining. Caspase 3 activity was measured using the caspase 3 activity assay kit. Expression of cyt-c, bcl-2, bax, AKT, and phosphorylated AKT was detected by western blot. Results: Exendin-4 reduced the percentage of cells undergoing apoptosis when β-cells were exposed to dexamethasone. Exendin-4 down-regulated caspase 3 activity, reduced cytochrome c levels in cytoplasm, and increased Bcl-2 protein levels and the Bcl-2 to Bax ratio in dexamethasone-treated β-cells. These exendin-4 effects were blocked in the presence of an inhibitor of the phosphoinositide-3 kinase (PI-3K) pathway or of the protein kinase A (PKA) pathway. Exendin-4 reversed dexamethasone-mediated inhibition of Akt phosphorylation, which was abrogated by the PI-3K and PKA inhibitors. Conclusion: PI-3K and PKA signaling are involved in the exendin-4-mediated modulation of β-cell apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors and the P2X3 subtype is an important candidate for this effect. Electroacupuncture (EA) has been clinically utilized to manage chronic pain. In this study, with neuropathic pain model of Sprague–Dawley (SD) rats, the P2X3 receptor protein level and expression location in the midbrain periaqueductal gray (PAG), a crucial site in endogenous pain modulatory system, were evaluated by Western blotting and immunohistochemistry. The results showed (1) pain thresholds were decreased while P2X3 receptor expression was up-regulated in the lateral PAG (lPAG) when neuropathic pain occurred. When the lPAG was pretreated with P2X3 receptors, antagonist A-317491 attenuated the antinociceptive effect produced by intra-lPAG injection of α,β-methylene-ATP (α, β-meATP), an agonist for P2X3 receptor. (2) Multiple EA treatments begot enhanced pain thresholds and increased P2X3 receptor immunoreactivity in the lPAG in neuropathic pain rats. Conversely, the down-regulated P2X3 receptor expression in the lPAG with antisense oligodeoxynucleotide (ODN) for P2X3 gene significantly attenuated the antinociceptive effect of EA treatment. These results suggest that P2X3 receptors in the lPAG play an inhibitory role in pain modulation and EA exerts a marked therapeutic effect in relieving neuropathic pain in CCI rats, which may be related to its regulative effect on the expression of P2X3 receptors in the lPAG. In conclusion, P2X3 receptors in the lPAG are involved in the supraspinal antiociception effect of EA treatment. [Copyright &y& Elsevier]