Fibrosis is a pathological wound healing process characterized by excessive extracellular matrix deposition, which interferes with normal organ function and contributes to ~ 45% of human mortality. ...Fibrosis develops in response to chronic injury in nearly all organs, but the a cascade of events leading to fibrosis remains unclear. While hedgehog (Hh) signaling activation has been associated with fibrosis in the lung, kidney, and skin, it is unknown whether hedgehog signaling activation is the cause or the consequence of fibrosis. We hypothesize that activation of hedgehog signaling is sufficient to drive fibrosis in mouse models.
In this study, we provide direct evidence to show that activation of Hh signaling via expression of activated smoothened, SmoM2, is sufficient to induce fibrosis in the vasculature and aortic valves. We showed that activated SmoM2 -induced fibrosis is associated with abnormal function of aortic valves and heart. The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves.
Our data show that activating hedgehog signaling is sufficient to drive fibrosis in mice, and this mouse model is relevant to human aortic valve stenosis.
Objective
This study shares our experience in managing adrenal schwannoma (AS).
Methods
The clinical data of eight patients with AS in our hospital from April 2007 to April 2022 were analyzed ...retrospectively.
Results
A total of 1309 patients with adrenal lesions were treated in the affiliated hospital of Guizhou Medical University for 15 years, of which only 8 cases were diagnosed as AS, accounting for 0.61%. Among the eight patients with AS, there were five females and three males, with an average age of 48.63 ± 12.05 years, and the average maximum diameter of the tumor was 6.96 ± 1.83 cm. All patients underwent adrenalectomy and were pathologically diagnosed as AS after the operation. The average follow-up time of eight patients with AS was 60.13 ± 22.33 months, and there was no recurrence or metastasis.
Conclusion
The retroperitoneum is an uncommon site for schwannoma tumors, and among adrenal incidentalomas, the schwannoma is rare. The disease lacks specific clinical and imaging features, but correct diagnosis before the pathological examination is very important for clinical management and surgical decision. When imaging examination indicates a slow-growing retroperitoneal mass, schwannoma should be considered. Surgical resection is the main treatment. Pathology is the gold standard for diagnosis. Most of the tumors are benign and have a good prognosis. There is a risk of recurrence after the operation, and it should be monitored actively.
Monolayered Ni-based layered double hydroxides (LDHs) enriched with hydroxyl vacancies are synthesized and first applied in the methanol-assisted energy-saving hydrogen production system including ...independent electrolysis and photovoltaic-electrolysis. The rich hydroxyl vacancies are revealed to endow monolayered LDHs with significantly superior performance in the aspects of the activity for methanol oxidation reaction and the boosting effect for cathodic hydrogen production compared to the bulk counterparts. The theoretical and experimental results confirm that the hydroxyl vacancies can increase density of states near Fermi level of LDH (i.e. elevate electrical conductivity to form favorable charge transportation during electrocatalysis), and promote its adsorption and further cleavage for methanol, thus leading to the enhanced methanol oxidation reaction performance.
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•Monolayered Ni-based LDHs with OH vacancies are applied in the methanol-assisted energy-saving hydrogen production.•Rich OH vacancies are revealed to endow monolayered LDHs with superior performance.•Enhancement mechanism associated with the OH vacancies existing in monolayered LDH is uncovered theoretically.
The GINS complex has been implicated in the prognosis of various cancers. It comprises four subunits, encoded by
,
,
, and
genes. Based on the current understanding, no report exists on the role of ...the GINS complex in pancreatic cancer.
We employed various bioinformatics databases including GEPIA, UALCAN, GEPIA2, and Kaplan Meier Plotter to identify the expression profile of the four genes (
,
,
, and
), their correlation with pancreatic cancer grade as well as their prognostic value of in pancreatic cancer. Western blotting and qRT-PCR analyses were conducted to verify the expression profiles of the four genes in pancreatic cancer. CCK8 and EdU cell experiments were conducted to reveal the role played by the four genes in pancreatic cancer cell proliferation.
Based on GEPIA, Western blotting, and qRT-PCR analyses, all the four genes in the GINS complex were overexpressed in pancreatic cancer. Notably, the expression of each member was significantly associated with pancreatic cancer grade. The prognostic analysis revealed that not only the whole GINS complex but also each individual were prognostic biomarkers for pancreatic cancer. CCK8 and EdU experiments demonstrated that inhibition of the expression of each GINS member lowered pancreatic cancer cell proliferation.
This work implicated
,
,
, and
genes as critical prognostic markers for pancreatic cancer.
The poor prognosis of cholangiocarcinoma in humans is related to several factors, such as (i) the heterogeneity of the disease, (ii) the late onset of symptoms and (iii) the limited comprehension of ...the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases.
With the increasing video on demand service need in broadcasting television and the development of triple play strategy, the next generation wireless network television system has been presented. ...With the advantages of interactive capability, next generation broadcasting-wireless (NGB-W) experiment network can cooperate with digital terrestrial multimedia broadcasting and China mobile multimedia broadcasting downlink systems. In this paper, the key technologies of NGB-W are described in detail. Application test and network deployment of NGB-W in Shanghai are presented to validate its extensive use.
Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). The enzymatic modification has ...been demonstrated to be highly regiospecific, forming proteinogenic para-Tyr (p-Tyr) exclusively. Here we biochemically characterized the first example of a phenylalanine 3-hydroxylase (Phe3H) that catalyzes the synthesis of meta-Tyr (m-Tyr) from Phe. Subsequent mutagenesis studies revealed that two residues in the active site of Phe3H (Cys187 and Thr202) contribute to C-3 rather than C-4 hydroxylation of the phenyl ring. This work sets the stage for the mechanistic and structural study of regiospecific control of the substrate hydroxylation by PheH.
What you watch and when you watch say a lot about you, and such information at the aggregated level across a user population obviously provides significant insights for social and commercial ...applications. In this paper, we propose a model for inferring household structures based on analyzing users' viewing behaviors in Internet Protocol Television (IPTV) systems. We emphasize extracting features of viewing behaviors based on the dynamic of watching time and TV programs and training a classifier for inferring household structures according to the features. In the training phase, instead of merely using the limited labeled samples, we apply semisupervised learning strategy to obtain a graph-based model for classifying household structures from users' features. We test the proposed model on China Telecom IPTV data and demonstrate its utility in census research and system simulation. The demographic characteristics inferred by our approach match well with the population census data of Shanghai, and the inference of household structures of IPTV users gives encouraging results compared with the ground truth obtained by surveys, which opens the door for leveraging IPTV viewing data as a complementary way for time- and resource-consuming census tracking. On the other hand, the proposed model can also synthesize trace data for the simulations of IPTV systems, which provides us with a new strategy for system simulation.
Background
The modular inner branched stent-graft (MIBSG) (WeFlow-Arch™) is an emerging device for challenging aortic arch pathologies. Hemodynamic numerical simulation is conducive to predicting ...long-term outcomes as well as optimizing the stent-graft design.
Objective
This study aims to analyze the hemodynamic characteristics of the MIBSG devices based on numerical simulation analyses.
Methods
From June 2019 to June 2021, MIBSGs were utilized in eight cases. Numerical simulation analyses of branch perfusion and indicators including the time-averaged wall shear stress, oscillatory shear index, and relative residence time were performed.
Results
Lesions involved Zone 1 (
n
= 2), Zone 2 (
n
= 4), and Zone 3 (
n
= 2). Branched stent-grafts were deployed in the innominate artery and left common carotid artery (
n
= 5) or in the innominate artery and left subclavian artery (
n
= 3). The hemodynamic change in common was increased perfusion in the descending aorta and left common carotid artery. Half of the patients had increased cerebral perfusion of 8.7% at most, and the other half of the patients showed a reduction of 5.3% or less. Case 3 was considered to have acquired the greatest improvement in hemodynamic features.
Conclusion
The MIBSG showed improved hemodynamic features in most cases. The design of the MIBSG could be partly modified to acquire better hemodynamic performance.
•A comprehensive approach was used to uncover potential flavor-contributing factors.•Highly correlated modules were identified, including blue, black, pink and turquoise.•Potential flavor ...constituents strongly associated with sensory attributes were given.•The influence of taste factors on olfactory characteristics were displayed.•This study provides a novel approach and valuable insights into flavor perception.
Flavor profiles of various Pyrus spp. cultivars exhibit significant variations, yet the underlying flavor-contributing factors remain elusive. In this investigation, a comprehensive approach encompassing metabolomics analysis, volatile fingerprint analysis, and descriptive sensory analysis was employed to elucidate the flavor disparities among Nanguoli, Korla fragrant pear, and Qiuyueli cultivars and uncover potential flavor contributor. The study comprehensively characterized the categories and concentrations of nonvolatile and volatile metabolites, and 925 metabolites were identified. Flavonoids and esters dominated the highest cumulative response, respectively. Utilizing weighted correlation network analysis (WGCNA), seven highly correlated modules were identified, yielding 407 pivotal metabolites. Further correlation analysis of the differential substances provided potential flavor constituents strongly associated with various sensory attributes; taste factors had a certain association with olfactory characteristics. Our findings demonstrated the manifestation of flavor was a result of the synergistic effect of various compounds; evaluation olfactory flavor necessitated a comprehensive consideration of taste substances.