Endorepellin remodels the endothelial transcriptome toward a pro-autophagic and pro-mitophagic gene signature.

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin protein ligase Parkin and the tumor suppressor mitostatin. Induction of both proteins required the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2). Furthermore, we discovered that endorepellin evoked mitochondrial depolarization in endothelial cells via a specific interaction between its two proximal LG1/2 domains and VEGFR2. We also found that following loss of membrane potential, mitostatin and parkin interact and that mitostatin associates with the established Parkin receptor mitofusin-2. In conclusion, we have identified a critical role for endorepellin in remodeling the autophagic transcriptome and influencing mitochondrial homeostasis

Awareness of interventional radiology before professional training and outcome measurement of an interventional radiology curriculum: a survey of third-year undergraduates in a Chinese medical college

PURPOSEWe aimed to assess the awareness of interventional radiology (IR) among medical students, and to evaluate an IR curriculum in China.METHODSBetween the academic years of 2008 and 2016, 517 third-year medical undergraduates, who successfully applied for an IR curriculum, received a survey related to IR before taking the course. Final exams were conducted after the IR course.RESULTSA total of 355 of the 517 medical students (68.67%) answered the survey; 81.97% of the respondents had heard of IR, 40.28% believed they understood what IR is, but no one was familiar with IR. The four most common pathways for medical students to acquire IR knowledge were via new media (e.g., internet, apps) (42.82%), a teacher/textbook (36.90%), a friend (32.68%), and traditional media (26.48%). The most familiar interventional procedures to respondents were percutaneous transluminal coronary angioplasty (PTCA, 78.59%) and transcatheter arterial chemoembolization (TACE, 44.51%). The results of the survey also indicated that 68.45% of the respondents wanted to learn about IR, but that only 47 male students (13.24%) considered a career in IR. The pass rate of the IR course final exam was 87.04%, i.e., 87.04% of the students successfully completed the course and final exam.CONCLUSIONThe IR knowledge of medical students in China is worse than that of European medical students. We suggest that providing medical students with general information about IR in the media, as well as via teaching and textbooks in medical school, requires prompt and significant attention. An IR curriculum is beneficial for increasing the IR knowledge of undergraduates

Domain Wall Conduction in Calcium-Modified Lead Titanate for Polarization Tunable Photovoltaic Devices

Ferroelectric domain wall (DW) conduction, confirmed in recent experiments, has attracted intense attention due to its promising applications in optoelec- tronic devices. Herein, we provide theoretical evidence of electric conduction in Pb0.8Ca0.2TiO3 (PCT) DWs. The separation of charge accumulation in DWs, corresponding to the electronic conduction-band minimum (CBM) and valence-band maximum (VBM), weakens the tendency for the electron-hole recombination, thereby providing more efficient channels for charge transfer. We fabricate PCT-based functional photovoltaic devices with polarization tunable charge transfer to exploit the combined conduction and ferroelectric properties of the DW. The photovoltaic performance of the devices can be regu- lated by the alternation of ferroelectric domains in PCT, caused by variation of the external poling. Our work broadens the applicability of DW conduction and may inspire the future design of high-performance materials in photovoltaic devices

The Tall Fescue Turf Grass Class I Chitinase Gene \u3cem\u3eFaChit1\u3c/em\u3e Is Activated by Fungal Elicitors, Dehydration, Ethylene, and Mechanical Wounding

The cDNA, genomic DNA, and promoter sequence of FaChit1, a class I chitinase gene from Festuca arundinacea, were isolated and characterized in the present work. The deduced amino acid sequence of FaChit1 contains the chitin binding, catalytic, and proline and glycine-rich domains characteristic for most class I chitinases, but no C-terminal extension region. FaChit1 is induced effectively by fungal elicitors, dehydration, and ethylene, but only slightly by mechanical wounding. To identify potential stress-related cis-acting elements, 5′ sequences 935, 651, and 233 bp upstream of the FaChit1 start codon were fused to the GUS reporter gene and analyzed in transgenic tobacco. The results indicated that the 935 bp fragment closely mirrored endogenous gene expression and that the 651 bp fragment was sufficient to direct reporter the gene expression in response to fungal elicitors, ethylene, dehydration, or mechanical wounding due to both known and presently uncharacterized cis-acting elements

Clinical, Cytogenetic, and Molecular Findings in Two Cases of Variant t(8;21) Acute Myeloid Leukemia (AML).

t(8;21)(q22;q22) is present in ~5–10% of patients with de novo acute myeloid leukemia (AML) and is associated with a better overall prognosis. Variants of the t(8;21) have been described in the literature, however, their clinical and prognostic significance has not been well-characterized. Molecular profiling of these cases has not previously been reported but may be useful in better defining the prognosis of this subset of patients. We present two cases of variant t(8;21) AML including clinical, cytogenetic, and molecular data

Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that decorin protein core modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin protein core to inhibit genes necessary for immunomodulatory responses while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic administration of decorin protein core and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties

Diuretic properties and chemical constituent studies on

The pharmacological evaluation demonstrated that the extracts from the stem of S. brachyanthera could significantly increase the outputs of urine of rats compared to those of furosemide treated group, and the effect could last for a longer period of time. The best effect appeared in the first two hours, which scientifically confirmed the diuretic effect of the plant. The comparative pharmacognosy study showed that the characters of the crude drugs of the stem of S. brachyanthera were similar to those of Akebia caulis. Further systemic work on its chemical constituents by chromatographic methods and NMR elucidations led to the isolation of 10 triterpenoids, 6 flavonoids, 4 lignanoids, and 3 phenylethanoid glycosides, whose structural types were much similar to those of A. quinata. Among them, 7 compounds were firstly reported in the genus of Stauntonia and calceolarioside B was the common characteristic constituent in both plants. From the similar pharmacognosy characters, pharmacological effects, and chemical constituents, it could be concluded that S. brachyanthera have a great possibility to be a succedaneum of Akebia caulis, whose supply is extremely short in recent years

A comparative study on the cyclic plasticity and fatigue failure behavior of different subzones in CrNiMoV steel welded joint

The cyclic plasticity and the low cycle fatigue failure behavior of the weld metal (WM) and base metal (BM) of the CrNiMoV steel welded joint under the strain and stress-control modes were investigated respectively. Significant cyclic softening was observed for both the WM and BM under the low cycle fatigue tests with the two control modes. Besides, obvious ratcheting happened in the WM and BM under the stress-controlled cyclic loading conditions. It is shown that both the WM and BM exhibited lower fatigue strength at the stress control mode than that at the strain control mode due to the influence of tension-compression asymmetry. Meanwhile, the WM showed larger cyclic softening rate, lower ratchetting deformation and fatigue strength than the BM under the same loading levels. The failure location of the WM specimens shifted from BM region (nearby the heat affected zone) to the center of WM with the increasing of strain amplitude under the strain-controlled tests, which can be explained with the similar maximum equivalent plastic strain amplitude location shifting behavior observed from the corresponding finite element simulations

Case Report: Clinicopathological Analysis of Minute Pulmonary Meningothelial-Like Nodules: Report of 7 Cases

ObjectiveTo investigate the clinical manifestations, radiologic features, pathological features, and immunophenotype of minute pulmonary meningothelial-like nodules (MPMNs).MethodThis is a retrospective observational study. We collected the clinical data of 7 cases of MPMNs, and performed comprehensive characterization using a combination of clinical, morphological, radiologic and immunohistochemical assessments.ResultsOf the 7 cases of MPMNs, 6 were female and 1 was male. The median age was 55 years. All MPMNs were multiple in lung with the size from 0,01 to 0,5cm. Chest CT examination showed ground-glass attenuation or solid nodules. Four cases were concomitant with carcinoma and/or pneumonia, and 3 cases occurred alone. Four of the 7 patients had no obvious symptoms; 3 patients had chest pain or cough or shortness of breath or hemoptysis. Multiple white nodules were found macroscopically, and the diseased cells grew along the alveolar septum, with relatively normal morphology, rich cytoplasm, unclear cell boundary, and uniform nucleus with delicate chromatin and without atypia; and the diseased cells showed nest or whorls distribution. EMA, PR, CD56 and vimentin were positive in all cases by immunohistochemistry.ConclusionsMPMNs are rare benign lesions in the lung, often multiple, usually less than 0.5cm in diameter, most of which have no obvious clinical symptoms. MPMNs are often found by chest CT, and occur independently or concomitant with other lesions. The positive immunohistochemical staining of EMA, PR, CD56, vimentin supports the diagnosis

Characterization and Clinical Significance of EIF1AX Mutations and Co-Mutations in Cytologically Indeterminate Thyroid Nodules: A 5-Year Retrospective Analysis.

OBJECTIVE: Mutations in the EIF1AX gene have been recently detected in a small percentage of benign and malignant thyroid lesions. We sought to investigate the prevalence and clinical significance of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. MATERIALS AND METHODS: A 5-year retrospective analysis was performed on thyroid nodules with a cytologic diagnosis of Bethesda category III or IV, which had undergone testing by our in-house next generation sequencing panel. Surgically resected nodules with EIF1AX mutations were identified, and mutation type and presence of co-mutations were correlated with histopathologic diagnosis. RESULTS: 41/904 (4.5%) cases overall and 26/229 (11.4%) surgically resected nodules harbored an EIF1AX mutation. The most common histologic diagnoses were follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma. 11/26 (42.3%) of nodules had isolated EIF1AX mutation. Comutations were found in RAS (12/26; 46.2%), TERT (5/26; 19.2%) and TP53 (2/26; 7.7%). EIF1AX mutation alone conferred a 36.4% risk of malignancy (ROM) and 54.5% ROM or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), while the ROM was significantly higher in nodules with concurrent RAS (71.4%), TERT, TP53 and RAS+TERT (100%) mutations. CONCLUSION: EIF1AX mutations occur in benign and malignant follicular thyroid neoplasms. In our cohort, the majority of mutations occurred at the splice acceptor site between exons 5 and 6. Importantly, the coexistence of EIF1AX mutations with other driver pathogenic mutations in RAS, TERT and TP53 conferred a 100% ROM or NIFTP, indicating that such nodules require surgical removal