Lattice QCD Calculation of Electroweak Box Contributions to Superallowed Nuclear and Neutron Beta Decays.

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR.

Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms. Methods: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1ß, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms. Results: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels. Conclusions: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.

Portal hypertension caused by pancreatic cancer: Multidetector computed tomography diagnosis and multivariate analysis of variceal hemorrhage.

CONTEXT: Pancreatic cancer portal hypertension (PCPH) is a rare cause of gastrointestinal bleeding. This study retrospectively assessed gastrointestinal bleeding risk factors in 57 PCPH patients diagnosed via multidetector computed tomography (MDCT). MATERIALS AND METHODS: The data of patients with pancreatic cancer from January 2008 to January 2018 at Qingdao Municipal Hospital were reviewed. PCPH patients were screened with MDCT and followed up. MDCT findings (e.g., the location of the venous obstruction, type of variceal veins pathway, and splenomegaly) were recorded. Variceal hemorrhage was recorded. The MDCT findings and clinical data of the PCPH patients were used in this analysis to explore the risk factors of variceal hemorrhage using binary logistic regression and multivariate logistic regression model. RESULTS: Fifty-seven of the 182 patients were diagnosed with PCPH. A total of 7 draining routes and 11 types of varices were found. Of these patients, eight experienced variceal hemorrhage. Univariate analysis showed that splenomegaly (odds ratio [OR] = 10.364, P = 0.003) was significantly associated with an increased risk of variceal hemorrhage. Multivariate analysis showed that splenomegaly (OR = 66.491, 95% confidence interval: 2.790-1584.643, P = 0.009) was an independent influencing factor for variceal hemorrhage in PCPH patients. CONCLUSIONS: Patients with pancreatic cancer have high morbidity of PCPH. The splenomegaly is more prone to hemorrhage. Splenomegaly was an independent risk factor of variceal hemorrhage. MDCT can provide insight into the stenosis and occlusion of the portal vein system and the drainage routes of variceal veins and is one of the best ways to diagnose PCPH.

High Glucose Level Induces Cardiovascular Dysplasia During Early Embryo Development.

The incidence of gestational diabetes mellitus (GDM) has increased dramatically amongst multiethnic population. However, how gestational diabetes mellitus damages the developing embryo is still unknown. In this study, we used yolk sac membrane (YSM) model to investigate angiogenesis in the developing chick embryo. We determined that in the presence of high glucose, it retarded the growth and extension of the embryonic vascular plexus and it also reduced the density of the vasculature in yolk sac membrane model. Using the same strategy, we used the chorioallantoic membrane (CAM) as a model to investigate the influence of high glucose on the vasculature. We established that high glucose inhibited development of the blood vessel plexus and the blood vessels formed had a narrower diameter than control vessels. Concurrent with the abnormal angiogenesis, we also examined how it impacted cardiogenesis. We determined the myocardium in the right ventricle and left atrium were significantly thicker than the control and also there was a reduction in glycogen content in cardiomyocytes. The high glucose also induced excess reactive oxygen species (ROS) production in the cardiomyocytes. We postulated that it was the excess reactive oxygen species that damaged the cardiomyocytes resulting in cardiac hyperplasia.

Stepwise stent deployment technique for tandem intracranial aneurysms: a review of 21 cases.

OBJECTIVES: We performed this study to report our experience using a stepwise stent deployment technique for the treatment of tandem intracranial aneurysms. METHODS: Patients with intracranial tandem aneurysms that were treated with a stepwise stent deployment technique between May 2009 and June 2013 were retrospectively reviewed. RESULTS: Twenty-one patients with 42 tandem aneurysms were identified (11 men, 10 women), with a mean age of 53.7 years (range, 17-82 years). Subarachnoid haemorrhage was confirmed in 12 patients using computed tomography at onset. Complete occlusion was achieved in 20 of the aneurysms (47.6%) after the procedure, neck remnant in 9 (21.4%), and aneurysm remnant in 13 (31.0%). The perioperative complications included in-stent thrombosis in one case and vasospasm in two cases, none of which left a permanent neurological deficit. The modified Rankin Scale (mRS) score at discharge was 0-2 in 20 cases and 3 in one case. The follow-up angiograms available for 17 patients showed complete occlusion in 26 aneurysms, improved in 4, and stable in 4. All of the patients had mRS scores of 0-1 during the clinical follow-up period. CONCLUSIONS: The stepwise stent deployment technique is feasible and helpful in the treatment of intracranial tandem aneurysms. KEY POINTS: • Treating wide-necked intracranial aneurysms with stent-assisted coiling is preferable. • Tandem wide-necked intracranial aneurysms can be treated with a single stent. • Stepwise stent deployment is technically feasible for embolizing tandem intracranial aneurysms.

Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development.

Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10(-8)-10(-6)µmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased in mesenchymal cell mass treated by low concentration of Dex. Mmp-13 expression was obviously up-regulated by Dex in both mesenchymal cells and primary chondrocyte cultures. And Col10a1 expression was also increased by Dex exposure in chondrocyte. In summary, we have revealed that different concentrations of Dex exposure during early gestation could exert a biphasic effect on vertebrate skeletal development.

Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo.

BACKGROUND: The developing embryo is very sensitive to oxidative stress and excess reactive oxygen species (ROS) generation is often associated with cardiovascular malformation. However, little is known about the adverse effects of ROS during heart morphogenesis, especially during the formation of the atria and ventricles. METHODS AND RESULTS: We have treated early chick embryos with 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH) to generate free radicals in the developing heart. We established that excess ROS induced by AAPH caused cardiomegaly to develop in 4-, 14- and 17-day-old embryos. The cardiomyocytes of these AAPH-treated hearts were hypertrophic, in both the compact and trabeculated myocardium. The weight of these hearts was also significantly increased in an AAPH dose-dependent fashion. We examined and compared the functions of the AAPH-treated and untreated hearts by echocardiography and determined that the ejection fraction was shortened. BrdU incorporation assay was performed and revealed that cell proliferation was not the main cause of cardiomegaly. However, we established that the cardiomyocytes exposed to excess ROS were distinctively larger than control cardiomyocytes - indicting that cardiomegaly was attributed to hypertrophy. We have also found that excess ROS inhibited Wnt signaling but enhanced VEGF signaling. Consequently, this promoted angiogenesis and caused larger coronary arteries to develop in the AAPH-treated hearts. CONCLUSIONS: We have demonstrated that cardiomyocyte hypertrophy and changes in Wnt and VEGF signaling were the main contributing factors in the development of cardiomegaly induced by oxidative stress.

A pivotal role of the vascular endothelial growth factor signaling pathway in the formation of venous hypertension-induced dural arteriovenous fistulas.

Dural arteriovenous fistulas (DAVFs) are associated with venous hypertension. Numerous studies have revealed high expression levels of vascular endothelial growth factor (VEGF) in human DAVF specimens, as well as in animal models of experimental venous hypertension. The objective of the present study was to clarify whether the VEGF signaling pathway is important in the development of DAVFs. Rats (n=216) were randomly divided into six groups. In the rats from five groups (groups A and C-E, n=45 in each group; group B, n=12), experimental venous hypertension was induced by right common carotid artery (CCA)­external jugular vein (EJV) anastomosis, superior sinus occlusion and left transver sinus occlusion, while the remaining group (group F, n=24) underwent sham surgery. The rats in group A received a VEGF recombinant adenovirus injection into the distal section of the right EJV 30 min prior to anastomosis of the CCA and EJV. An equivalent control adenovirus was injected into the right EJV of group B rats prior to anastomosis. The rats in group C received no virus prior to anastomosis and no medicine subsequent to surgery. The group D rats were lavaged with Vatalanib, a VEGF receptor (VEGFR) inhibitor, and the group E rats were lavaged with an equal quantity of saline weekly following surgery. Six rats from groups A-E and one rat from group F were sacrificed in the first, second, fourth and twelfth weeks after surgery for immunohistochemical analysis of VEGF expression and analysis of microvessel density. Cerebral angiography was performed on the remaining rats in each group on the twelfth week after surgery. The results revealed that following transfection with VEGF recombinant adenovirus, angiogenesis in the dura mater of venous hypertensive rats was increased subsequent to the increase in the VEGF expression levels of the brain and dura mater. The rate of DAVF induction by venous hypertension was significantly reduced by the VEGFR antagonist due to reduced angiogenesis in the dura mater. In conclusion, VEGF and its receptor may be important in the formation of venous hypertension-induced DAVFs.

The negative influence of high-glucose ambience on neurogenesis in developing quail embryos.

Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologically, such that neural tube defects (NTDs) developed. In addition, we found that high glucose impaired nerve differentiation at dorsal root ganglia and in the developing limb buds, as revealed by neurofilament (NF) immunofluorescent staining. The dorsal root ganglia are normally derived from neural crest cells (NCCs), so we examine the delamination of NCCs from dorsal side of the neural tube. We established that high glucose was detrimental to the NCCs, in vivo and in vitro. High glucose also negatively affected neural differentiation by reducing the number and length of neurites emanating from neurons in culture. We established that high glucose exposure caused an increase in reactive oxidative species (ROS) generation by primary cultured neurons. We hypothesized that excess ROS was the factor responsible for impairing neuron development and differentiation. We provided evidence for our hypothesis by showing that the addition of vitamin C (a powerful antioxidant) could rescue the damaging effects of high glucose on cultured neurons.

Exposure to 2,5-hexanedione can induce neural malformations in chick embryos.

Worldwide, n-hexane is an organic solvent widely used in numerous industries such as chemical engineering, pharmaceutical and cosmetic industry. 2,5-Hexanedione (2,5-HD) is the main metabolite of n-hexane. It is now gradually recognized that chronic exposure to n-hexane could harm the health of people. Nevertheless, it is still unclear whether or not 2,5-HD is potentially teratogenic during pregnancies. In this study, we investigated the effects of 2,5-HD exposure on embryonic development in the chick embryo. We first determine the effect of 2,5-HD on neurodevelopment - specifically looking for neural tube defects in the forebrain, midbrain, and also for malformation in the eyes. We established that in the presence of 2,5-HD, the dorsal neural tubes were malformed during the closure of the neural folds. In addition, exposure to 2,5-HD could also inhibit neural differentiation as revealed by immunofluorescent staining for neurofilament (NF). We also demonstrated that the impaired neurodevelopment was attributed to negative effect of 2,5-HD on neurite development and positive effect on apoptosis in developing neurons. Specifically, we found 2,5-HD treatment resulted in fewer neurons and the neurites projecting from the neurons were significantly shorten when compared with control cultures. In addition, MTT and mitochondrial membrane potential (MMP) assays revealed neuron cell viability was reduced by exposure to 2,5-HD in a dose-dependent fashion. In sum, our results suggest that chronic exposure to 2,5-HD is harmful to the developing embryo, especially in the context of neurodevelopment.

Effects of D-cycloserine on extinction and reinstatement of morphine-induced conditioned place preference.

d-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl-d-aspartate (NMDA) receptor complex, has been shown to facilitate the extinction and prevent the relapse of cocaine-induced conditioned place preference (CPP) when administered before or after each extinction trail. However, some studies have suggested that DCS does not influence or even enhance relapse of seeking behavior on cocaine self-administration (SA) in rats or cocaine-dependent individuals undergoing clinical exposure treatment. Furthermore, there are no reports on the effects of DCS and the extinction of morphine-conditioned behaviors in mice. The present study investigated the effects of DCS on extinction by exposing mice to drug-paired cues and the subsequent reinstatement of morphine-primed CPP. Our results showed that DCS at doses of 7.5, 15, and 30mg/kg did not induce conditioned appetitive or aversive effects and DCS combined with morphine conditioning failed to affect the acquisition of morphine-induced CPP. Moreover, pretreatment with DCS (7.5, 15, and 30mg/kg, i.p.) prior to extinction training had no significant effects on the extinction and subsequent morphine-primed reinstatement of morphine-induced CPP. These results suggested that DCS may not be a powerful adjunct for cue exposure therapy of opioid addiction. In view of differing outcomes in both preclinical and clinical studies, the potential of DCS in exposure treatment of drug-seeking behaviors should be carefully evaluated.