Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma.Although specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to treat.Consequently,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug development.This investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were identified.Gene Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent groups.Validation through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma patients.In TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to TMz.Mechanistically,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ubiquitination.This,in turn,elevated ITPKB stability and impaired ROS production.Furthermore,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse model.These findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

Design of luminescence in(Sr,Gd)Li(Al,Mg)_(3)N_(4):Eu^(2+)deep red phosphors via crystal field engineering for full-spectrum WLEDs

Red phosphor,with longer wavelength,is highly desirable for full-spectrum WLEDs.Targeted deep red phosphors(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+)were designed from the initial model of SrLiAl_(3)N_(4):Eu^(2+)by structural modification.The correlations among structural evolution,crystal-field environment,and luminescence properties were elucidated.Replacing Sr^(2+)with Gd^(3+)in(Sr,Gd)LiAl_(3)N_(4):Eu^(2+)leads to the enhanced crystal field splitting,larger Stokes shift,and increased structural polyhedron distortion differences,consequently resulting in spectral red-shift and broadening.For further spectral tuning,Mg,with lower electronegativity,was also introduced to modify the local crystal structure,consequently resulting in a further red-shift towards 675 nm and enhanced photoluminescence intensity in(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+).What’s more,w-LEDs were fabricated by using blue LED chip,blue,green,red and deep red((Sr,Gd)Li(Al,Mg)_(3)N_(4):Eu^(2+))phosphors whose color rendering index were Ra 96.0 and R997.7.All above results demonstrate that the partial replacements of Sr^(2+)by Gd^(3+)and Al^(3+)by Mg^(2+)are effective methods for spectral modulation and(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+)phosphors are suitable for highquality full-spectrum WLEDs.

Synthesis, structure and luminescent properties of yellow phosphor La3Si6N11 ：Ce^3＋ for high power white-LEDs

A series of high phase purity blue light excitable yellow-emitting LaSiN:xCephosphors were synthesized by the high temperature solid state reactions method. The structure and luminescent properties were investigated. The phase structure was studied by means of X-ray diffraction, structures refinements and energy dispersive X-ray spectroscopy. The phosphors effectively excited by the light of450 nm and show intense yellow emission at 535 nm with FWHM of 115 nm corresponding to the5 d →~2 Fand 5 d →~2 Ftransitions of Ce. In addition,the optimized LaSiN:0.14 Ceexhibits a weak thermal quenching, which remains 98.2% of the initial emission intensity when heated to 200 ℃,the thermal quenching properties exhibit a modest decline when the temperature returned to room temperature. The above results indicate that LaSiN:Cecan be regarded as a high promising phosphor for applications in high power white-light LED.

White-light emitting single-phase phosphor La_3Si_6N_(11):Dy^(3+),Tb^(3+):Color tunable emission, thermal stability and energy transfer process

A novel white-light emitting single-phase phosphor La_3 Si_6 N_(11):Dy^(3+),exhibiting two emission peaks centering at 475 and 575 nm, was prepared via conventional solid-state reactions. The structure and morphology of La_3 Si_6 N_(11):Dy^(3+)/Tb^(3+) were investigated by X-ray diffraction(XRD) and scanning electron microscopy(SEM). The emission colors can be tuned from white to yellow-green through increasing the Tb^(3+) concentration in La_3 Si_6 N_(11):Dy^(3+),Tb^(3+), The mechanism of energy transfer(ET) from Dy^(3+) to Tb^(3+) is confirmed according to the excitation,emission spectra and decay lifetimes curve. The temperaturedependent luminescence measurements of La_(2.83)Si_6 N_(11):0.1 Dy^(3+),0.07 Tb^(3+) were also performed, and a good thermal stability is shown, suggesting superior properties for the application as white lightemitting diodes(w-LEDs) phosphor.

Broadband near-infrared luminescence and energy transfer of Cr^(3+),Ce^(3+) co-doped Ca_(2)LuHf_(2)Al_(3)O_(12) phosphors

Broadband near-infrared phosphors are highly desirable for food testing.Targeted Ca_(2)LuHf_(2)Al_(3)O_(12):Cr^(3+)(CLHA:Cr^(3+)) and Ca_(2)LuHf_(2)Al_(3)O_(12):Ce^(3+),Cr^(3+)(CLHA:Ce^(3+),Cr^(^(3+))) phosphors were synthesized by the conventional high-temperature solid state reaction.The CLHA:Cr^(3+)phosphor,with a good thermal stability,shows a red shift owing to radiation reabsorption and non-radiative transition with increasing Cr^(3+)content.For co-doped sample,the emission intensity of Cr^(3+)can be enhanced by three times due to the energy transfer from Ce^(3+)to Cr^(3+),which can be evidenced by a significant overlap between the PLE of Cr^(3+)single-doped phosphor and the PL of Ce^(3+)single-doped phosphor.In addition,the mechanism of energy transfer is identified as a quadrupole-quadrupole interaction according to decay Lifetime and Dexter’s energy transfer formula.The broadband NIR emission peaked at 775 nm of CLHA:Cr^(3+),Ce^(3+)phosphor shows a bright prospect in nondestructive quality-control analysis systems for food.

Green and red phosphor for LED backlight in wide color gamut LCD

Wide color gamut(WCG) backlight for liquid crystal display(LCD) utilizing white light-emitting diodes(LED) has attracted considerable attention for their high efficiency and color reduction.In this review,recent developments in crystal structure,luminescence and applications of phosphors for wide color gamut LED backlight are introduced.As novel red phosphors,Mn4+activate fluoride and aluminate phosphors are advanced in quantum efficiency,thermal quenching and color saturation for their characteristic spectrum with broad excitation band and linear emission.The crystal structure and fluorescence properties of Mn4+doped fluosilicate,fluorogermanate,fluotitanate,as well as Sr4 Al14O25,CaAl12O19 and BaMgAl10O17 phosphors are discussed in detail.A serial of narrow-band red-emitting Eu2+,Eu3+and Pr3+-doped nitride silicates and molybdate phosphors are also introduced.Rare-earth-doped oxynitride and silicate green-emitting phosphors have attracted more and more attention because of the wide excitation,narrow emission,high quenching temperature,high quantum efficiency,such as β-sialon:Eu2+,Ba3Si6O12N2:Eu2+,MSi2O2N2:Eu2+(M=Ca,Sr,Ba),y-AlON:Mn2+and Ca3Sc2Si3O12:Ce3+.All above phosphors demonstrate their adaptability in wide color gamut LCD display.Especially for Mn4+doped fluosilicate red phosphor and β-sialon:Eu2+green phosphor.To achieve an ultra-high color gamut in white LED backlight and against the OLED,innovative narrow-band-emission red and green phosphor materials with independent intellectual property rights are continuously pursed.

Carbon interstitial defects causing emission red shift in YAG:Ce phosphor:First-principles calculation

Y3Al5O12:Ce3+ is the most famous phosphor material due to its excellent photolumincent properties.Here,through first-principles calculation,the effect of carbon interstitial defects on Y3Al5O12:Ce3+phosphor was investigated. It is found that the carbon interstitials tend to occupy the next-nearest sites of Ce3+ion in Y3Al5O12:Ce3+ lattice. Specially,these interstitial defects can shorten the Ce3+-O2-bond length, leading to a larger crystal field splitting of 5 d orbital of the Ce3+atom and bigger 5 d centroid shift.These two factors cause the emission spectrum of Y3Al5O12(C):Ce3+red shift compared with that of Y3Al5O12:Ce3+. Moreover, with our comparison experiment, we find that the Y3Al5O12(C):Ce3+ has an obvious red shift compared with that of Y3Al5O12:Ce3+system,which is in accord with our first principles calculation. Our work systematically investigates the impact of the carbon interstitial defect on Y3Al5O12:Ce3+,and provides a new route to tune the emission spectrum in Y3Al5O12:Ce3+.

Enhanced luminescence performances of Mn^(4+)-activated Sr_(4)Al_(14)O_(25)red phosphors by doping with Sc^(3+)ions

A series of non-rare earth Mn^(4+)-activated strontium aluminate phosphors Sr_(4)Al_(14)O_(25):Mn^(4+)co-doped with Sc^(3+)ions were successfully synthesized by a high-temperature solid-state reaction method.XRD result reveals that there is no introduction of additional phase but expansion of lattice with incorporation of Sc34 ions.Excitation and emission spectrum measurement shows that the synthesized phosphors can be efficiently excited by near-ultraviolet and blue light,and a deep red emission centered at 652 nm with a narrow full width at half maximum(FWHM)can be obtained,which is attributed to the transition^(2)E→^(4)A_(2)of Mn^(4+)ions.In addition,the crystal field strength parameter(Dq)and Racah parameters(B,C)and energies of states were calculated based on experimental data.Moreover,the luminous intensity of Sr_(4)Al_(14-x)SCxO_(25):Mn^(4+)is enhanced and increased by 60%compared with Mn^(4+)single incorporated sample at x=0.06.A phenomenon of redshift is observed in the excitation spectrum and discussed systematically.Finally,the mechanism of the positive effects with Sc^(3+)ions incorporated into lattice is discussed in detail.All the results suggest that the Sr_(4)Al_(13.94)Sc_(0.06)O_(25):Mn^(4+)phosphor will become one of the great candidates for backlight of LCD.

Nickel-Catalyzed Cross-Coupling of Aryl Pivalates with Cyclobutanols Involving C-O and C-C Bond Cleavage

of main observation and conclusion An efficient nickel-catalyzed cross-coupling of aryl pivalates with cyclobutanols is described.The use of Ni(cod)2/PCy3/base as the catalytic system enables the cleavage of inert C—0 bond and C—C bond under mild conditions,thus providing a facile access to y-arylated ketones in generally good to excellent yields.This transformation is also characterized by wide substrate scope and functional group compatibility,for example,methoxy,γ-dimethylamino,keto,ester,fluoro and TMS groups are well-tolerated during the reaction process.

Effect of fluxes on synthesis and luminescence properties of BaSi_2O_2N_2:Eu^(2+) oxynitride phosphors

Eu^2＋ activated BaSi2 O2 N2 oxynitride bluish-green phosphor was synthesized adopting conventional high-temperature solid-state reaction method, in which BaF2, Na2 CO3 and NH4 Cl were used as the fluxes.The phase formation, size distribution and microscopic morphology were characterized to investigate the influence of adding fluxes on photo luminescence properties. The results indicate that with the addition of BaF2 flux, the particle morphology becomes regular and size distribution narrows and the phase purity of BaSi2 O2 N2：Eu^2＋ phosphor can be improved effectively. The photoluminescence intensity of BaSi2 O2 N2：Eu^2＋ phosphor with BaF2 as flux gets enhanced obviously, which is much higher than that of Na2 CO3, NH4 Cl and without flux. The optimum content of BaF2 flux is 4 wt%, and the maximum photoluminescence intensity of the BaSi2 O2 N2：Eu^2＋ phosphor prepared with BaF2 flux rises to 141%,meanwhile, the phosphors with BaF2 flux exhibits low thermal quenching. The results indicate that the BaSi2 O2 N2：Eu^2＋ is sort of promising bluish-green phosphor for application in full-spectra LED.

Luminescent properties of Ce^(3+),Er^(3+) co-doped La_3Si_6N_(11)

In order to obtain near-infrared phosphor pumped by blue chip with high luminous efficiency, a novel near-infrared phosphor Ce^(3+)/Er^(3+) doped La_3Si_6N_(11) was designed and firstly prepared via conventional solid-state reactions. The structure and morphology of Ce^(3+)/Er^(3+) doped La_3Si_6N_(11) were investigated by X-ray diffraction(XRD) and scanning electron microscopy(SEM). Compared with Er^(3+) doped La_3Si_6N_(11),the emission intensity of the Ce^(3+), Er^(3+) co-doped phosphor can be increased more than 5 times.Meanwhile, the mechanism of energy transfer from Ce^(3+) to Er^(3+) is confirmed according to the excitation,emission spectra and decay lifetimes curve. Above results suggest that La_3 Si_6 N_(11):Ce^(3+),Er^(3+) is a promising near-infrared phosphor for blue pumped LEDs(light-emitting diodes).

Blue-emitting Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+) phosphors for high CRI white LEDs

A broadband blue-emitting Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+)(x=0-0.2) phospho rs were synthesized,which can be used for near-UV pumped white light-emitting diodes(w-LEDs).The crystal structures,photoluminescence pro perties,external quantum efficiency,the rmal stability and application perfo rmance of Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+),by partially substituting Sr^(2+) with Ca^(2+)(x=0-0.2),were studied by various analytical techniques.When the Ca/Sr ratio of Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+) gradually increases,the emission peak of Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+) red-shiftes from 459 to 465 nm,corrected external quantum efficiency increases from 31.8% to 42.9%,and the thermal stability is also improved.The mechanism of the changes of the photoluminescence emission and excitation spectra,external quantum efficiency and thermal stability properties was also investigated in detail.In addition,a w-LED was fabricated by using SrLu_(2)O_(4):Ce^(3+)(blue),β-sialon:Eu^(2+)(green) and(Sr,Ca)AlSiN_(3):Eu^(2+)(red) phosphors combined with a 405 nm near-UV LED chip,and its color rendering index(CRI) reaches 96.0.When Sr_(0.8)Ca_(0.2)Lu_(2)O_(4):Ce^(3+) is applied as blue phosphor to substitute SrLu_(2)O_(4):Ce^(3+),the obtained w-LED devices have high luminous efficiency,and CRI greater than 95.0.These re sults show that the Sr_(1-x)Ca_(x)Lu_(2)O_(4):Ce^(3+) can be potential blue phosphors for n-UV pumped high CRI w-LEDs application.

Nickel-Catalyzed Direct Coupling of Allylic Alcohols with Organoboron Reagents

The direct coupling of allylic alcohols with arylboronic acids or their derivatives catalyzed by Ni（cod）2 in the presence of a catalytic amount of base has been developed. A wide variety of allylic substrates or aryIboronic acids turned out to be applicable to this catalytic system. The present method does not require the use of ligands for stabilizing the nickel catalyst in most cases or additional activators for activation of altylic alcohols.