CHRM3 is a novel prognostic factor of poor prognosis andpromotes glioblastoma progression via activation of oncogenicinvasive growth factors

Glioblastoma(GBM)is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy.Clarification of molecular mechanisms of GBM’s characteristic invasive growth is urgently needed to improve the poor prognosis.Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor(CHRM3)were significantly higher in the recurrent samples than in the primary samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis,consistent with The Cancer Genome Atlas database.Knockdown of CHRM3 inhibited GBM cell growth and invasion.An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time.Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth,including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8.Taken together,CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.

Inconsistency of changes in uniaxial compressive strength and P-wave velocity of sandstone after temperature treatments

It is generally accepted that the uniaxial compressive strength(UCS)and P-wave velocity of rocks tend to decrease simultaneously with increasing temperature.However,based on a great number of statistical data and systematic analysis of the microstructure variation of rocks with temperature rising and corresponding propagation mechanism of elastic wave,the results show that(1)There are three different trends for the changes of UCS and P-wave velocity of sandstone when heated from room temperature(20C or 25C)to 800C:(i)Both the UCS and P-wave velocity decrease simultaneously;(ii)The UCS increases initially and then decreases,while the P-wave velocity decreases continuously;and(iii)The UCS increases initially and then fluctuates,while the P-wave velocity continuously decreases.(2)The UCS changes at room temperaturee400C,400Ce600C,and 600Ce800C are mainly attributed to the discrepancy of microstructure characteristics and quartz content,the transformation plasticity of clay minerals,and the balance between the thermal cementation and thermal damage,respectively.(3)The inconsistency in the trends of UCS and P-wave velocity changes is caused by the change of quartz content,phase transition of water and certain minerals.

Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma

Objective:O6 methylguanine-DNA methyltransferase(MGMT)promoter methylation is a biomarker widely used to predict the sensitivity of IDH-wildtype glioblastoma to temozolomide therapy.Given that the IDH status has critical effects on the survival and epigenetic features of glioblastoma,we aimed to assess the role of MGMT promoter methylation in IDH-mutant glioblastoma.Methods:This study included 187 IDH-mutant glioblastomas and used 173 IDH-wildtype glioblastomas for comparison.KaplanMeier curves and multivariate Cox regression were used to study the predictive effects.Results:Compared with IDH-wildtype glioblastomas,IDH-mutant glioblastomas showed significantly higher(P<0.0001)MGMT promoter methylation.We demonstrated that MGMT promoter methylation status,as determined by a high cutoff value(≥30%)in pyrosequencing,could be used to significantly stratify the survival of 50 IDH-mutant glioblastomas receiving temozolomide therapy(cohort A);this result was validated in another cohort of 25 IDH-mutant glioblastomas(cohort B).The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases,and 18.37 and 41.61 months for methylated cases,and in cohort B were 6.97 and 9.10 months for unmethylated cases,and 23.40 and 26.40 months for methylated cases.In addition,we confirmed that the MGMT promoter methylation was significantly(P=0.0001)correlated with longer OS in IDH-mutant patients with GBM,independently of age,gender distribution,tumor type(primary or recurrent/secondary),and the extent of resection.Conclusions:MGMT promoter methylation has predictive value in IDH-mutant glioblastoma,but its cutoff value should be higher than that for IDH-wildtype glioblastoma.

Optimum Location of Tube Blank in Electromagnetic Bulging

Using analytical method, this paper gets 'the mutual inductance between coil and workpiece in tube blank electromagnetic bulging. According to this, we obtain the optimum locations of tube blank with different length of coil and workpiece. There is a good agreement between results calculated and the experimental data.

2-switched Er^(3+)/Dy^(3+)codoped ZrF_(4)fiber laser:continuously tunable pulse generation from 3.06 to 3.62μm

In this Letter,we report on widely tunable pulse generation from a red-diode-clad-pumped mid-infrared[mid-IR)Er^(3+)/Dy^(3+)codoped ZrF_(4)fiber laser,for the first time,to the best of our knowledge.Using a Fe^(2+):ZnSe crystal,continuously tunable Qswitched pulses across the range of 3.06–3.62μm have been attained,which not only represents the widest range[in wavelength domain)from a pulsed rare-earth-doped fiber laser at any wavelength,but also almost entirely covers the strong absorption band of C-H bonds in the mid-IR,providing a potential way for gas detection and polymer processing.In addition,the commercial InAs quantum-well-based saturable absorbers[SAs)have been employed instead,and the obtained longest Q-switching wavelength of 3.39μm is slightly shorter than 3.444μm determined by its nominal direct bandgap of 0.36 eV.

In-situ fabricated anisotropic halide perovskite nanocrystals in polyvinylalcohol nanofibers: Shape tuning and polarized emission

We report an in-situ fabrication of halide perovskite (CH3NH3PbX3,CH3NH3 =methylammonium,MA,X =Cl,Br,I) nanocrystals in polyvinylalcohol (PVA) nanofibers (MAPbX3@PVA nanofibers) through electrospinning a perovskite precursor solution.With the content of the precursors increased,the resulting MAPbBr3 nanocrystals in PVA matrix changed the shape from ellipsoidal to pearl-like,and finely into rods-like.Optimized MAPbBr3@PVA nanofibers show strong polarized emission with the photoluminescence quantum yield of up to 72%.We reveal correlations between the shape of in-situ fabricated perovskite nanocrystals and the polarization degree of their emission by comparing experimental data from the single nanofiber measurements with theoretical calculations.Polarized emission of MAPbBr3@PVA nanofibers can be attributed to the dielectric confinement and quantum confinement effects.Moreover,nanofibers can be efficiently aligned by using parallel positioned conductor strips with an air gap as collector.A polarization ratio of 0.42 was achieved for the films of well-aligned MAPbBr3@PVA nanofibers with a macroscale size of 0.5 cm × 2 cm,which allows potential applications in displays,lasers,waveguides,etc.

Intratumor heterogeneity,microenvironment,and mechanisms of drug resistance in glioma recurrence and evolution

Glioma is the most common lethal tumor of the human brain.The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months.The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas.Unlike primary glioblastoma that usually develop de novo in the elderly,secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis.Based on various evolutional trajectories brought on by clonal and subclonal alterations,the evolution patterns of glioma vary according to different theories.Some important features distinguish the normal brain from other tissues,e.g.,the composition of the microenvironment around the tumor cells,the presence of the blood-brain barrier,and others.The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer.Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment.However,the detailed reasons for the progression and recurrence of glioma remain controversial.In this review,we introduce the different mechanisms involved in glioma progression,including tumor heterogeneity,the tumor microenvironment and drug resistance,and their pre-clinical implements in clinical trials.This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.

Estimating posterior inference quality of the relational infinite latent feature model for overlapping community detection

Overlapping community detection has become a very hot research topic in recent decades,and a plethora of methods have been proposed.But,a common challenge in many existing overlapping community detection approaches is that the number of communities K must be predefined manually.We propose a flexible nonparametric Bayesian generative model for count-value networks,which can allow K to increase as more and more data are encountered instead of to be fixed in advance.The Indian buffet process was used to model the community assignment matrix Z,and an uncol-lapsed Gibbs sampler has been derived.However,as the community assignment matrix Zis a structured multi-variable parameter,how to summarize the posterior inference results andestimate the inference quality about Z,is still a considerable challenge in the literature.In this paper,a graph convolutional neural network based graph classifier was utilized to help tosummarize the results and to estimate the inference qualityabout Z.We conduct extensive experiments on synthetic data and real data,and find that empirically,the traditional posterior summarization strategy is reliable.

Molecular pathology and clinical implications of diffuse glioma

The prognosis for diffusely infiltrating gliomas at World Health Organization(WHO)grade 2-4 remains dismal due to their heterogeneity.The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification.Thus,the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas.Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma,including surgery,radiotherapy and chemotherapy,targeted therapy,immunotherapy,and more precision clinical trials.Herein,we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice.We also review the advances in molecular features of gliomas,which can facilitate the development of glioma therapies,thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.

Pump phase transfer and its control in hybrid seeded optical parametric amplifiers

Due to the existence of spatial walk-off and/or group-velocity mismatch effects, pump-to-signal phase transfer becomes inevitable during parametric amplification. We experimentally demonstrate that in hybrid seeded optical parametric amplifiers(OPAs) that include two OPA stages seeded by the signal and idler waves, respectively, the phase of the output signal can be restored to its initial value, although there are spatial and temporal phase fluctuations on the pump source. This method significantly relaxes the requirement for high pump beam quality, which is always very stringent in parametric amplification systems. With the introduction of this scheme into birefringent phase-matching OPAs or chirped-pulse OPAs, it should be promising to achieve intense femtosecond laser pulses that are close to the diffraction limit in space and ultra-high contrast in time, simultaneously.