Objective To investigate the effects of JSH⁃23 combined with Stattic targeting inhibition of nuclear factor⁃κB (NF⁃κB) and signal transducer and activator of transcription factor 3 (STAT3) signaling ...pathways on the proliferation and migration ability of mesenchymal glioblastoma cells and the expressions of NF⁃κB pathway and STAT3 pathway⁃related proteins. Methods The mRNA⁃seq results of 529 glioma patients were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatics was used to analyze the correlation between RelA/P65 and STAT3 and the markers of mesenchymal glioblastoma, as well as the expression of NF⁃κB pathway and STAT3 pathway⁃related proteins in mesenchymal, classical and proneural glioblastoma. The human glioma cell lines U87MG and U251MG in vitro were treated with JSH⁃23, Stattic, JSH⁃23 and Stattic, respectively. The half⁃inhibitory concentration (IC50) of the two drugs was calculated by cytotoxicity assay, and the synergistic effect of the two drugs was observed by drug synergistic assay. CCK
ObjectiveTo explore the mechanism of FGFR3⁃TACC3 (F3⁃T3) fusion gene mediating DNA damage repair through promoting pyruvate kinase M2 (PKM2)'s nuclear translocation in glioblastoma. MethodsThe ...lentiviral transfection technology was used to constructed stable transitional cell lines U87MG cells and U251MG cells that stably expressing F3 ⁃ T3 and empty vector. In vivo glioblastoma model was constructed by intracranial in situ tumor implantation in athymic mice, and the tumorigenic ability of F3⁃T3 transfected cells in athymic mice of each treatment group was observed by small⁃animal in vivo imaging system. Bioinformatics analysis was performed to analyze gene microarray data exploring the possible biological functions of F3 ⁃ T3 mediating chemoresistance and identify the relationship between survival expectations and PKM2 expression levels in glioblastoma patients from The Cancer Genome Atlas (TCGA) database. Transient transfection of small interference RNA (siRNA) was used to knock down the expression of PKM2 in the F3 ⁃ T3 transfected cells. Proliferative activity of U87MG and U251MG cells treated with different concentrations of temozolomide (TMZ), transfected with siRNA, and TMZ in combination with Compound 3k, a PKM2 inhibitor, was observed in CCK ⁃ 8 cell proliferation assays. Nuclear and cytoplasmic proteins were extracted separately and PKM2 protein expression was observed in whole cell extract, cytoplasmic extract and cytosolic extract after TMZ treatment. Relative expression of PKM2, relative expression of cytosolic phosphorylated histone H2AX (p⁃H2AX) and relative expression of siRNA knockdown PKM2 gene in U87MG and U251MG cells stably expressing the F3 ⁃ T3 fusion gene, detected by Western blotting. Results1) CCK⁃8 cell proliferation assay showed that the survival rate of U87MG cells in the F3 ⁃ T3 transfected group was higher than that in the empty vector transfected group after treatment with TMZ 640, 320, 160, 80, 40 μmol/L (P = 0.000, 0.000, 0.000, 0.000, 0.004, 0.010), and the survival rate of U251MG cells in the F3 ⁃ T3 transfected group was also higher than that in the empty vector transfected group after TMZ 640, 320, 160, 80, 40, 20, 5 μmol/L (P = 0.000, 0.000, 0.000, 0.002, 0.001, 0.002); the survial rate of U87MG cells in the si⁃PKM2⁃1009 transfected group was lower than that of F3 ⁃ T3 transfected group after TMZ 640, 320, 160, 80, 40, 20, 10, 5, 2.50 μmol/L, the survival rate of U251MG cells in the si⁃PKM2⁃1377 transfected group was also lower than that in F3⁃T3 transfected group after TMZ 640, 320, 160, 80, 40, 20, 5 μmol/L (P = 0.000, 0.000, 0.002, 0.000, 0.002, 0.048, 0.042); and the survival rate of U87MG cells in TMZ + Compound 3k group was lower than TMZ group after TMZ 640, 320, 160, 80, 40, 20 μmol/L (P = 0.000, 0.000, 0.000, 0.000, 0.001, 0.002), and the survival rate of U251MG cells in TMZ + Compound 3k group after treatment with high concentrations of TMZ (640, 320, 160, 80 and 40 μmol/L) was also lower than TMZ group (P = 0.000, 0.000, 0.000, 0.000, 0.003), while the survival rate of U251MG cells in TMZ + Compound 3k group after treatment with low concentrations of TMZ (10, 5 and 2.50 μmol/L) was higher than that of TMZ group (P = 0.000, 0.000, 0.006). 2) An animal model of glioblastoma showed the presence of TMZ resistance in homozygous mice. 3) Bioinformatic analysis showed that the biological function of F3⁃T3 was significantly enriched in the DNA repair pathway (P = 0.000). Survival and overall survival of glioblastoma patients in the TCGA database were lower in the PKM2 high expression group than in the low expression group (P < 0.05). 4) Western blotting showed that the relative expression of p⁃H2AX in U87MG (P = 0.000, 0.000, 0.004) and U251MG (P = 0.000, 0.007, 0.005) cells in the F3 ⁃ T3 transfected group were lower than those in the empty vector transfected group after TMZ treatment for 48 h and then medium change for 24, 36 and 48 h. PKM2 protein incorporation into the nucleus was observed in both U87MG and U251MG cells in the F3⁃T3 transfected group after TMZ treatment, whereas it was not observed in cells in the empty vector transfected group; si⁃PKM2⁃1009 and si⁃ PKM2⁃1377 knocked down the relative expression of p⁃H2AX in U87MG (P = 0.000, 0.001, 0.006) and U251MG (P = 0.000, 0.000, 0.000) cells, respectively. ConclusionsIn the presence of TMZ, F3 ⁃ T3 promotes PKM2's nuclear translocation and activates DNA damage repair pathways, which in the eventually results resistance of glioblastoma cell to TMZ. PKM2 inhibitors can compromise the resistance glioblastoma cells stably expressing F3⁃T3 fusion gene to TMZ.
Objective To investigate the effects of JSH⁃23 combined with Stattic targeting inhibition of nuclear factor⁃κB (NF⁃κB) and signal transducer and activator of transcription factor 3 (STAT3) signaling ...pathways on the proliferation and migration ability of mesenchymal glioblastoma cells and the expressions of NF⁃κB pathway and STAT3 pathway⁃related proteins. Methods The mRNA⁃seq results of 529 glioma patients were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatics was used to analyze the correlation between RelA/P65 and STAT3 and the markers of mesenchymal glioblastoma, as well as the expression of NF⁃κB pathway and STAT3 pathway⁃related proteins in mesenchymal, classical and proneural glioblastoma. The human glioma cell lines U87MG and U251MG in vitro were treated with JSH⁃23, Stattic, JSH⁃23 and Stattic, respectively. The half⁃inhibitory concentration (IC50) of the two drugs was calculated by cytotoxicity assay, and the synergistic effect of the two drugs was observed by drug synergistic assay. CCK⁃8 assay and colony⁃forming assay were used to detect the proliferation activity of tumor cells. Wound healing assay and Transwell assay were used to detect the migration ability of tumor cells. Western blotting was used to detect the relative expressions of NF⁃κB pathway and STAT3 pathway⁃related proteins P65, phosphorylated P65 (p⁃P65), STAT3, phosphorylated STAT3 (p⁃STAT3) and CD44. Results 1) Bioinformatics analysis showed that RelA/P65 mRNA and STAT3 mRNA were positively correlated with mesenchymal glioblastoma markers CD44, CXCR4, CHI3L1, IL⁃4R and TRADD (r=0.206-0.605; P＜0.01, for all); the expressions of NF⁃κB pathway and STAT3 pathway⁃related proteins in mesenchymal glioblastoma were the highest, followed by classical glioblastoma, and the lowest in proneural glioblastoma. 2) The cytotoxicity assay showed the IC50 of JSH⁃23 on U87MG and U251MG cells were 59.39 and 56.21 μmol/L, and Stattic were 0.96 and 1.08 μmol/L. The drug synergistic assay showed that the synergistic effect of JSH⁃23 at 40-80 μmol/L and Stattic at 0.50-1 μmol/L on U87MG was the highest, and the synergistic effect of JSH⁃23 at 40 μmol/L and Stattic at 1 μmol/L on U251MG was the highest. The final concentration of JSH⁃23 was 60 μmol/L and Stattic was 1 μmol/L. 3) After the combined treatment of JSH⁃23, Stattic, JSH⁃23 and Stattic, the proliferation activity of U87MG and U251MG cells decreased (P=0.000, for all), the colony forming efficiency decreased (P=0.000, for all), the cell mobility decreased (P＜0.05, for all), and the positive cell numbers of crystal violet staining decreased (P=0.000, for all). The relative expressions of P65 (P=0.000, for all), p⁃P65 (P=0.000, for all), STAT3 (P=0.000, for all), p⁃STAT3 (P=0.000, for all) and CD44 (P=0.000, for all) were decreased, especially after JSH⁃23 combined with Stattic treatment (P＜0.01, for all). Conclusions JSH⁃23 combined with Stattic targeting inhibition of NF⁃κB and STAT3 signaling pathways can effectively inhibit the proliferation and migration ability of mesenchymal glioblastoma cells, and down⁃regulate the relative expressions of NF⁃κB pathway and STAT3 pathway⁃related proteins.
Purpose： The aim of this study was to determine whether PET （positron emission tomography） imaging parameters from simultaneous ^11C-choline PET/MRI （magnetic resonance imaging） could be used to ...characterize primary prostate cancer. Methods： Forty-six patients with biopsy-proven high-risk prostate cancer （clinical T stage ≥ cT2c, a Gleason score 〉 8, or PSA （prostate-specific antigen） level 〉 20 ng/mL） were prospectively enrolled. A SUV （standardized uptake value） histogram analysis including maximum SUV, mean SUV, SUV variance, SUV entropy, MTV （metabolic tumor volume）, and UVP （uptake volume product） was applied for the calculation of PET imaging parameters. Correlations between the PSA level and Gleason score were then evaluated. Results： Maximum SUV, mean SUV, MTV, UVP, and SUV variance were significantly correlated with PSA level, whereas SUV variance was the only parameter negatively correlated with the Gleason score. Multivariate logistic regression analysis demonstrated that MTV and PSA level at diagnosis were independent predictors of positive distant metastasis status. Conclusions： PET imaging parameters from simultaneous ^11C-choline PET/MRI were correlated with PSA level. However, ^11C-choline metabolic tumor heterogeneity was not associated with biospecimen-derived Gleason scores in prostate cancer. To apply PET texture quantification analysis to prostate cancer, a more specific PET radiotracer is required.
A novel strategy for the asymmetric construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones via an intramolecular vinylogous Rauhut–Currier reaction of ...para-quinone methides (p-QMs) under the bifunctional catalysis of chiral amine-phosphine is described. This intramolecular mode for the catalytic enantioselective 1,6-conjugate addition of p-QMs has been explored for the first time, delivering two types of synthetically important heterocycles in high yields and enantioselectivites.
A novel base-mediated tandem spirocyclopropanation/rearrangement reaction of vinyl p-quinone methides (p-VQMs) with sulfonium salts is described. The unprecedented reactivity of p-VQMs was explored ...for the first time in the spiroannulation cascade, providing a stereoselective approach to the construction of synthetically interesting, densely functionalized spirocyclopentenyl p-dienones.
Percutaneous vertebroplasty (VP) provides substantial benefit to patients with painful osteoporotic vertebral compression fractures (OVCF). However, the reoccurrence of vertebral fracture after VP is ...a major concern. The purpose of this study is to conduct a meta-analysis on the incidence of subsequent fractures after VP in patients with OVCF. PubMed and EMBASE were searched. In addition, we scrutinized the reference list of all relevant articles to supplement the database search. We included original articles reporting on new fracture rates after VP in OVCF patients. Subsequent fracture rates were pooled across studies using a random-effects meta-analysis. Thirty-nine studies with a total of 8047 participants from 12 countries were included in this meta-analysis. Patients’ age ranged from 64.2 to 94.6 years (reported by 31 studies). The median follow-up was 21 months (36 studies). Pooled estimate for subsequent fractures after VP was 23.4% (95% CI, 19.8–27.2%;
I
2
= 93.0%,
p
< 0.01). New fractures after VP in 54.6% of cases occurred in the vertebral bodies adjacent to the treated vertebra (95% CI, 49.0–60.1%;
I
2
= 66.0%,
p
< 0.01). A significant proportion of patients undergoing VP for OVCF experience new fractures after treatment, most of which are developed in the vertebral bodies adjacent to the treated vertebra.
This study deals with an extensive taxonomic reevaluation focusing on phylogenetic relationships and morphological characterization of Tubeufiales, especially those helicosporous hyphomycetes which ...are difficult to identify. Based on evidence from DNA sequence data and morphology, we introduce 13 new genera in the family Tubeufiaceae,
viz. Acanthotubeufia
,
Dematiohelicoma
,
Dematiohelicomyces
,
Dematiohelicosporum
,
Dematiotubeufia
,
Helicoarctatus
,
Helicohyalinum
,
Helicotruncatum
,
Neochlamydotubeufia
,
Neohelicoma
,
Pleurohelicosporium
,
Pseudohelicomyces
and
Pseudohelicoon
; transfer
Chaetosphaerulina
from Dothideomycetes genera
incertae sedis
, and
Artocarpomyces
and
Helicodochium
from Ascomycetes genera
incertae sedis
into Tubeufiaceae; introduce 52 new species,
viz. Berkleasmium fusiforme
,
B. longisporum
,
Chlamydotubeufia cylindrica
,
Dematiohelicosporum guttulatum
,
Helicoarctatus aquaticus
,
Helicodochium aquaticum
,
Helicohyalinum infundibulum
,
Helicoma aquaticum
,
H. brunneisporum
,
H. cocois
,
H. rufum
,
H. fusiforme
,
H. longisporum
,
H. multiseptatum
,
H. rubriappendiculatum
,
H. septoconstrictum
,
H. tectonae
,
Helicomyces hyalosporus
,
Helicosporium aquaticum
,
H. flavisporum
,
H. setiferum
,
H. vesicarium
,
H. viridiflavum
,
Neochlamydotubeufia fusiformis
,
Neohelicomyces hyalosporus
,
Neohelicosporium acrogenisporum
,
N. astrictum
,
N. ellipsoideum
,
N. irregulare
,
N. krabiense
,
N. laxisporum
,
N. ovoideum
,
Pleurohelicosporium parvisporum
,
Pseudohelicomyces aquaticus
,
P. hyalosporus
,
Tubeufia abundata
,
T. bambusicola
,
T. brevis
,
T. brunnea
,
T. chlamydospora
,
T. dictyospora
,
T. eccentrica
,
T. fangchengensis
,
T. hechiensis
,
T. inaequalis
,
T. krabiensis
,
T. rubra
,
T. sessilis
,
T. sympodihylospora
,
T. sympodilaxispora
,
T. taiwanensis
and
T. tratensis
; provide 43 new combinations,
viz. Acanthohelicospora guianensis
,
Acanthotubeufia filiforme
,
Berkleasmium aquatica
,
B. guangxiense
,
B. latisporum
,
B. thailandicum
,
Dematiohelicoma perelegans
,
D. pulchrum
,
Dematiohelicomyces helicosporus
,
Dematiotubeufia chiangraiensis
,
Helicohyalinum aquaticum
,
Helicoma elinorae
,
H. gigasporum
,
H. hongkongense
,
H. linderi
,
H. nematosporum
,
H. pannosum
,
H. serpentinum
,
Helicomyces chiayiensis
,
Helicotruncatum palmigenum
,
Neochlamydotubeufia khunkornensis
,
Neohelicoma fagacearum
,
Neohelicomyces pallidus
,
Neohelicosporium abuense
,
N. aurantiellum
,
N. griseum
,
N. morganii
,
N. myrtacearum
,
N. nizamabadense
,
N. sympodiophorum
,
N. taiwanense
,
N. vesiculiferum
,
Pseudohelicomyces indicus
,
P. paludosus
,
P. talbotii
,
Pseudohelicoon gigantisporum
,
P. subglobosum
,
Tubeufia dentophora
,
T. geniculata
,
T. lilliputea
,
T. machaerinae
,
T. sympodiophora
and
T. xylophila
; introduce 16 new records,
viz. Dictyospora thailandica
,
Helicomyces colligatus
,
H. torquatus
,
Neohelicosporium guangxiense
,
N. hyalosporum
,
N. parvisporum
,
Thaxteriellopsis lignicola
,
Tubeufia aquatica
,
T. chiangmaiensis
,
T. cylindrothecia
,
T. filiformis
,
T. guangxiensis
,
T. laxispora
,
T. parvispora
,
T. roseohelicospora
and
T. tectonae
. The taxonomy of
Helicoma
,
Helicomyces
and
Helicosporium
is revisited based on phylogenetic analyses and morphological evidence.
Neorhamphoria
is transferred to Bezerromycetaceae. Three species are excluded from the genus
Chlamydotubeufia
, twelve species from
Helicoma
, four species from
Helicomyces
, 25 species from
Helicosporium
, six species from
Neoacanthostigma
and one species from
Tubeufia
. A multi-gene phylogenetic tree based on maximum likelihood and Bayesian analyses of ITS, LSU, RPB2 and TEF1α sequence data of species of Tubeufiales is provided. Detailed descriptions and illustrations are provided, as well as the morphological comparison with similar taxa are explored. The checklist of accepted Tubeufiales species and re-organised Tubeufiales species are provided.
Among solution-processed photovoltaic materials, lead sulfide (PbS) colloidal quantum dots (QDs) possess a highly tunable bandgap and strong infrared absorption, while metal halide perovskites show ...extraordinary external quantum efficiency (EQE) in the visible region, which offers the opportunity to construct an ideal tandem cell of PbS QDs/perovskite. However, it still remains a huge challenge to integrate fragile perovskite films into a monolithic tandem structure. We have for the first time addressed the challenge of preparing stable and efficient tandem solar cells combining PbS colloidal QDs with emerging MAPbI 3 perovskites by all-solution-processing. A perfectly superimposed open circuit voltage and an optimal power conversion efficiency (PCE) of 11.03% have been achieved, which is the highest reported PCE for any PbS QD based tandem solar cell. And we believe this efficiency will be further improved by using perovskites with wider bandgaps to provide more complementary absorption. In addition, the introduction of a PbS subcell can effectively eliminate the hysteresis-effect in metal-halide perovskites, and result in high UV stability and exceptional storage stability under a dry environment without encapsulation. Therefore, we revealed that the synergetic use of QDs and perovskite materials in tandem structures can extend the range of device photo response and simultaneously deliver excellent device performance as well as improved stability. Moreover, our work provided an important starting point for future advances in efficient QDs/perovskite tandem solar cells with more complementary absorption.
