A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

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 for TMZ-resistant GBM.

FHOD1 is upregulated in glioma cells and attenuates ferroptosis of glioma cells by targeting HSPB1 signaling.

BACKGROUND: As a new type of regulatory cell death, ferroptosis has been proven to be involved in cancer pathogenesis and therapeutic response. However, the detailed roles of ferroptosis or ferroptosis-associated genes in glioma remain to be clarified. METHODS: Here, we performed the TMT/iTRAQ-Based Quantitative Proteomic Approach to identify the differentially expressed proteins between glioma specimens and adjacent tissues. Kaplan-Meier survival was used to estimate the survival values. We also explored the regulatory roles of abnormally expressed formin homology 2 domain-containing protein 1 (FHOD1) in glioma ferroptosis sensitivity. RESULTS: In our study, FHOD1 was identified to be the most significantly upregulated protein in glioma tissues. Multiple glioma datasets revealed that the glioma patients with low FHOD1 expression displayed favorable survival time. Functional analysis proved that the knockdown of FHOD1 inhibited cell growth and improved the cellular sensitivity to ferroptosis in glioma cells T98G and U251. Mechanically, we found the up-regulation and hypomethylation of HSPB1, a negative regulator of ferroptosis, in glioma tissues. FHOD1 knockdown could enhance the ferroptosis sensitivity of glioma cells via up-regulating the methylated heat-shock protein B (HSPB1). Overexpression of HSPB1 significantly reversed FHOD1 knockdown-mediated ferroptosis. CONCLUSIONS: In summary, this study demonstrated that the FHOD1-HSPB1 axis exerts marked regulatory effects on ferroptosis, and might affect the prognosis and therapeutic response in glioma.

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1+ ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1+ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1+ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

The Aurora Kinase Inhibitor TAK901 Inhibits Glioblastoma Growth by Blocking SREBP1-Mediated Lipid Metabolism.

Glioblastoma (GBM) is the most common and lethal malignant primary brain tumor. The standard treatment for GBM including surgical resection followed by radiation therapy and adjuvant chemotherapy with temozolomide remains unsatisfactory. In this study, we investigated the effects of the Aurora kinase inhibitor, TAK901, in GBM both in vitro and in vivo, and explored its key downstream targets. The effects of TAK901 were investigated using cell viability, cell apoptosis, live/dead, cell cycle, Transwell, 3D cell invasion, neuro-sphere, and self-renewal assays. Mechanistic studies were conducted using RNA-seq, lipid measurements, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blotting. The in vivo efficacy of TAK901 was validated using orthotopic xenograft GBM mouse models. In both GBM cells and GSCs, TAK901 remarkably reduced cell viability, self-renewal, migration and invasion and induced apoptosis and cell cycle arrest. Treatment with TAK901 considerably inhibited GBM growth in vivo. RNA-seq and RT-qPCR analyses showed that TAK901 downregulated the expression and activation of SREBP1. Moreover, SREBP1 overexpression alleviated the TAK901-mediated suppression of cell viability and apoptosis in GBM cells. Our results provide evidence that TAK901 inhibits GBM growth by suppressing SREBP1-mediated lipid metabolism.

Extracellular signal-regulated kinase in the basolateral amygdala is required for reconsolidation of heroin-associated memory.

Reconsolidation of heroin-associated memory is an independent memory process that occurs following retrieval, which is essential for the sustained capacity of an associative drug stimulus to precipitate heroin-seeking. Extracellular signal-regulated kinase (ERK) in the basolateral amygdala (BLA) mediates the reconsolidation of drug memory. In the present study, we utilized a rat model of drug craving and relapse to verify the hypothesis that the reconsolidation of heroin-associated memory requires ERK in an instrumental heroin-seeking behavior, focusing on the BLA brain region, which is crucial for synaptic plasticity and memory processes. We found that bilateral intra-BLA infusions of U0126 (1 µg/0.5 µl), an ERK inhibitor, immediately after retrieving heroin-associated memory significantly reduced cue-induced and drug-induced reinstatement and spontaneous recovery of heroin-seeking compared to the vehicle. Furthermore, this inhibitory effect was related to the characteristic of reconsolidation. Conversely, no effect was observed on the heroin-seeking behavior when the intra-BLA infusion of U0126 was administered 6 h after the heroin-associated memory retrieval or without memory retrieval. Together, these data suggest that disrupting the reconsolidation of heroin-associated memory via an ERK inhibitor may serve as a promising option for treating relapse in opiate addicts.

Identification of ACSF gene family as therapeutic targets and immune-associated biomarkers in hepatocellular carcinoma.

Acyl-CoA synthetases (ACSs) are responsible for acyl-CoA synthesis from nonpolar hydrophilic fatty acids and play a vital role in many metabolic processes. As a category of ACS isozymes, members of ACS family (AACS, ACSF2-3, AASDH) participate in lipid metabolism; however, their expression patterns, regulatory mechanisms and effects in hepatocellular carcinoma (HCC) are poorly understood. Here, through evaluating the expression profiles of ACSF gene family, we found that upregulated AACS might be more significant and valuable in development and progression of HCC. Consequently, the mRNA expression levels of AACS and ACSF2 was accordantly increased in HCC. Kaplan-Meier plotter revealed that HCC patients with high level of AACS were highly related to a shorter overall survival time and relapse-free survival. Genetic alterations using cBioPortal revealed that the alteration rate of AACS were 5%. We also found that the functions of ACSF gene family were linked to several cancer-associated pathways, including long-term potentiation, phospholipase D signaling pathway and purine metabolism. TIMER database indicated that the AACS and ACSF2 had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, Diseasemeth database revealed that the global methylation levels of ACSF2 was higher in HCC patients. In conclusion, this study firstly demonstrated that Acyl-CoA synthesis gene family, in particular, AACS, could be associated with immune microenvironment, thereby influencing the development and prognosis of patients with HCC.

Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior.

Drug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending on the basolateral amygdala (BLA). Pharmacology or behavior treatment that disrupts the reconsolidation can effectively attenuate drug-seeking in addicts. Here, we hypothesized that heroin-memory reconsolidation requires cAMP-dependent protein kinase A (PKA) of BLA based on the fundamental effect of PKA in synaptic plasticity and memory process. After 10 days of acquisition, the rats underwent 11 days of extinction training and then received the intra-BLA infusions of the PKA inhibitor Rp-cAMPS at different time windows with/without a reactivation session. The results show that PKA inhibitor treatment in the reconsolidation time window disrupts the reconsolidation and consequently reduces cue-induced reinstatement, heroin-induced reinstatement, and spontaneous recovery of heroin-seeking behavior in the rats. In contrast, there was no effect on cue-induced reinstatement in the intra-BLA infusion of PKA inhibitor 6 h after reactivation or without reactivation. These data suggest that PKA inhibition disrupts the reconsolidation of heroin-associated memory, reduces subsequent drug seeking, and prevents relapse, which is retrieval-dependent, time-limited, and BLA-dependent.

Double-Layered Strategy for Broadband Photomultiplication-Type Organic Photodetectors and Achieving Narrowband Response in Violet, Red, and Near-Infrared Light.

Broadband photomultiplication-type organic photodetectors (PM-OPDs) were prepared with PMBBDT:PY3Se-2V (1:1, wt/wt) as the absorbing layer (AL) and PC71BM:P3HT (100:5, wt/wt) as the photomultiplication layer (PML) on the basis of the sandwich structure. The incident photons from ultraviolet light to the near-infrared region can be harvested by AL. The rather less P3HT in PML can produce plenty of isolated hole traps with P3HT surrounded by PC71BM; the electron tunneling injection induced by trapped holes near the Ag electrode can lead to the photomultiplication (PM) phenomenon. The performance of PM-OPDs can be effectively improved by optimizing the AL thickness. The optimal PM-OPDs exhibit a broad spectral response from 300 to 1050 nm as well as an external quantum efficiency (EQE) of 5800% at 340 nm at 10 V bias, along with a specific detectivity (D*) of 3.78 × 1013 Jones. The spectral response of PM-OPDs is controlled by the trapped-hole distribution near the Ag electrode, primarily originating from the photogenerated holes in AL. To further optimize the spectral response of PM-OPDs, the optical filter layer (OFL) was used to manipulate light field distribution in AL. The violet, red, and near-infrared-light PM-OPDs were developed by employing different OFLs.

Inhibition of Glycogen Synthase Kinase 3ß Activity in the Basolateral Amygdala Disrupts Reconsolidation and Attenuates Heroin Relapse.

Exposure to a heroin-associated conditioned stimulus can reactivate drug reward memory, trigger drug cravings, and induce relapse in heroin addicts. The amygdala, a brain region related to emotions and motivation, is involved in processing rewarding stimulus. Recent evidence demonstrated that disrupting the reconsolidation of the heroin drug memories attenuated heroin seeking which was associated with the basolateral amygdala (BLA). Meanwhile, neural functions associated with learning and memory, like synaptic plasticity, are regulated by glycogen synthase kinase 3 beta (GSK-3ß). In addition, GSK-3ß regulated memory processes, like retrieval and reconsolidation of cocaine-induced memory. Here, we used a heroin intravenous self-administration (SA) paradigm to illustrate the potential role of GSK-3ß in the reconsolidation of drug memory. Therefore, we used SB216763 as a selective inhibitor of GSK-3ß. We found that injecting the selective inhibitor SB216763 into the BLA, but not the central amygdala (CeA), immediately after heroin-induced memory retrieval disrupted reconsolidation of heroin drug memory and significantly attenuated heroin-seeking behavior in subsequent drug-primed reinstatement, suggesting that GSK-3ß is critical for reconsolidation of heroin drug memories and inhibiting the activity of GSK-3ß in BLA disrupted heroin drug memory and reduced relapse. However, no retrieval or 6 h after retrieval, administration of SB216763 into the BLA did not alter heroin-seeking behavior in subsequent heroin-primed reinstatement, suggesting that GSK-3ß activity is retrieval-dependent and time-specific. More importantly, a long-term effect of SB216763 treatment was observed in a detectable decrease in heroin-seeking behavior, which lasted at least 28 days. All in all, this present study demonstrates that the activity of GSK-3ß in BLA is required for reconsolidation of heroin drug memory, and inhibiting GSK-3ß activity of BLA disrupts reconsolidation and attenuates heroin relapse.

YTH domain family: potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common high malignancy with insidious onset, invasive fast-growing, high recurrence rate and fatality. YTH domain family plays essential roles in development of HCC. However, the biological function of YTH domain family in HCC have not been clarified. Here, through evaluating the expression profiles of YTH domain family, we found that upregulated YTHDF1 might be more significant and valuable in development and progression of HCC. There was a strong correlation between YTHDC1, YTHDF1 and YTHDF2 and pathological stage of HCC patients. Kaplan-Meier plotter revealed that HCC patients with high level of YTHDF1 and YTHDF2 were highly related to a shorter overall survival time, and low level of YTHDF1 (p = 0.0017) has an important association with a longer progression-free survival time. Genetic alterations using cBioPortal revealed that the alteration rates of YTHDF3 were the highest. We also found that the functions of YTH domain family were linked to several cancer-associated pathways, including peptidyl-serine modification, peptidyl-tyrosine modification and negative regulation of cellular component movement. TIMER database indicated that the YTH domain family had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, Ualcan databases revealed that the global methylation levels of YTHDC1 was higher in HCC patients, while YTHDF2 was lower in HCC patients. In conclusion, our findings will enhance the understanding of YTH domain family in HCC pathology, and provide novel insights into YTH-targeted therapy for HCC patients.

Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma.

BACKGROUND: The regulatory roles of long non-coding RNA (lncRNA) CRNDE in temozolomide (TMZ) chemoresistance to glioblastoma multiforme (GBM) are still poorly understood. Therefore, the function, characteristics, and possible mechanism of CRNDE in TMZ-induced chemoresistance to GBM were explored. METHODS: Firstly, the expression level of CRNDE in 58 cases of glioma tissue specimens and 30 cases of normal brain tissues were tested by qRT-PCR. Meanwhile, the correlation between CRNDE expression level, the clinicopathological characteristics, and survival time of patients with glioma were analyzed. Then, the CRNDE expression in various glioma cell lines was detected, and CRNDE knockdown cell models were constructed. Subsequently, to explore the effect of CRNDE on chemosensitivity to TMZ, cell viability was detected by the CCK-8 assay and IC50 values, and cell proliferation was detected by cell clone assay and EdU assay, as well as cell survival was detected by apoptosis with flow cytometry under TMZ treatment. Further, the expression of drug-resistance protein ABCG2, autophagy related proteins, and PI3K/Akt/mTOR pathway were measured by western blot or qRT-PCR in TMZ-treated glioma cells. Finally, the mouse tumor xenograft model was established and the tumor volume and weight were measured, and ABCG2 expression was conducted by immunohistochemistry assay. RESULTS: The integrated results demonstrated lncRNA CRNDE was a poor prognosis factor for GBM patient, which was upregulated in patients who were resistant to TMZ, and closely associated with chemotherapeutic response status to TMZ treatment. Further, functional assays revealed that knockdown of CRNDE could notably reduce glioma cell viability and proliferation, and elevate cell apoptosis to enhance the chemosensitivity to TMZ in vitro and in vivo. Mechanistically, the depression of CRNDE could diminish the expression of LC3 II/I, Beclin1 and Atg5 and increase the p62 expression level to inhibit autophagy due to the activation of PI3K/Akt/mTOR pathway as well as highly correlated with ABCG2 expression. CONCLUSIONS: Overall, the study provided that lncRNA CRNDE is a reliable clinical predictor of outcome and prognosis and a potential biomarker for predicting TMZ treatment response in GBM by modulating the autophagy through PI3K/Akt/mTOR pathway and ABCG2 expression which may be a novel therapeutic target for regulating TMZ sensitivity to GBM.

Smart Strategy: Transparent Hole-Transporting Polymer as a Regulator to Optimize Photomultiplication-type Polymer Photodetectors.

Photomultiplication-type polymer photodetectors (PM-PPDs) were fabricated with hole-only transport active layers containing polymer(s): [6,6]-phenylC61-butyric acid methyl ester (PC61BM) with a weight ratio of 100:2. The rather less PC61BM content in active layers prefers to generate a large amount of isolated electron traps surrounded by polymers. Photogenerated electrons prefer to be trapped by the isolated PC61BM due to the lack of continuous electron-transport channels. The trapped electrons by the isolated PC61BM close to the Al electrode would like to seduce hole tunneling injection. The transparent polymer poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)benzidine] (poly-TPD) was incorporated as a regulator to improve hole mobility (µh) and adjust the trapped-electron distribution in active layers, leading to the enhanced performance of PM-PPDs. The optimal PM-PPDs were achieved using poly(3-hexylthiophene) (P3HT):poly-TPD:PC61BM (80:20:2, wt/wt/wt) as active layers. External quantum efficiency (EQE) values at 620 nm are 3900 and 1250% for PM-PPDs based on P3HT:poly-TPD:PC61BM (80:20:2, wt/wt/wt) and P3HT:PC61BM (100:2, wt/wt) under -10 V applied voltage, respectively. The EQE at 620 nm of optimal PM-PPDs is improved from 650 to 63,000% along with the applied voltage increase from -5 to -20 V. This work provides a new strategy of using transparent polymer with large µh as a regulator for EQE and response speed improvement, as well as the flattened EQE spectral shape of PM-PPDs.

Ultra-Narrow-Band NIR Photomultiplication Organic Photodetectors Based on Charge Injection Narrowing.

Ultra-narrow-band NIR photomultiplication organic photodetectors (PM-OPDs) were realized in ITO/PEDOT:PSS/active layers/Al based on an interfacial-trap-induced charge injection narrowing (CIN) concept. The rather less Bod Ethex-Hex (BEH) is imbedded in a polymer donor matrix to form large amounts of isolated electron traps. Trapped electrons in BEH close to an Al electrode will enforce hole-tunneling injection induced by interfacial band bending, resulting in a photomultiplication phenomenon. PM-OPDs with P3HT:BEH as the active layer exhibit a narrow response peak at 850 nm with a full-width at half-maximum (fwhm) of 27 nm as well as a rather weak response from 650 to 800 nm. The EQE of 29 700% at 850 nm was achieved in PM-OPDs by incorporating 0.02 wt % of F6TCNNQ under -13 V of applied voltage. The rejection ratio (RR) of the optimized PM-OPDs with F6TCNNQ is 11 for EQE850 nm/EQE700 nm and 10 for EQE850 nm/EQE750 nm, respectively. An EQE of 15 300% at 850 nm was achieved in the ternary PM-OPDs under -13 V of applied voltage, with markedly enhanced RRs of 44 for EQE850 nm/EQE700 nm and 30 for EQE850 nm/EQE750 nm.

Broadband photomultiplication organic photodetectors.

Broadband photomultiplication organic photodetectors (PMOPDs) can be achieved with a double-layered active layer prepared from IEICO-4F : PBDB-T blend solutions with different weight ratios (1 : 1 or 3 : 100, wt/wt). The response range of the double-layered PMOPDs covers from 310 nm to 930 nm, determined by the photon harvesting range of the IEICO-4F : PBDB-T (1 : 1, wt/wt) layer. The IEICO-4F : PBDB-T (3 : 100, wt/wt) layer was used as a PM layer in the double-layered PMOPDs, achieving external quantum efficiency (EQE) more than 100% based on the work mechanism of trap-assisted hole tunneling injection. The trapped electrons in PBDB-T/IEICO-4F/PBDB-T near the Al electrode will makeinterfacial-band-bending to narrow the injection barrier, resulting in hole-tunneling-injection from the external circuit. The polymer PBDB-T can provide an efficient charge transport channel for the injected hole from the external circuit. The specific detectivity (D*) and responsivity (R) of the double-layered PMOPDs are 1.05 ± 0.03 × 1012 Jones and 0.94 ± 0.03 A W-1 at 810 nm under a -10 V bias, respectively.

CPS1 expression and its prognostic significance in lung adenocarcinoma.

BACKGROUND: Studies have increasingly shown that carbamoyl phosphate synthetase 1 (CPS1) plays a vital role in the occurrence and development of human malignant disease. Unfortunately, the detailed function of CPS1 in the development and prognosis of lung cancer, especially lung adenocarcinoma (LADC), is still not fully understood. In this research, we performed a comprehensive bioinformatics analysis with respect to the function of CPS1 in human LADC. METHODS: Several biological databases including UALCAN, GEPIA and Oncomine were used to analyze the expression of CPS1 in LADC. Meanwhile, TCGA and GEO databases were utilized to analyze relevant clinical data. In addition, databases including Methsurv, etc., were used to analyze CPS1 methylation levels in LADC. RESULTS: The Oncomine platform, UALCAN and gene expression profiling interactive analysis (GEPIA) were used and revealed that the expression levels of CPS1 were significantly increased in LADC tissues. Furthermore, we analyzed the methylation level of CPS1 in LADC and found that cases with high levels of CPS1 showed hypomethylated CPS1. The clinical data from the Wanderer database, which is linked to The Cancer Genome Atlas (TCGA) database, demonstrated that the expression and methylation values of CPS1 were both significantly related to the clinical characteristics and prognosis of LADC. Through analysis of the dataset from the Gene Expression Omnibus (GEO) database, we found that the expression level of CPS1 was markedly downregulated in human A549 lung cancer cells treated with the chemotherapeutic drug motexafin gadolinium (MGd) in a time-dependent manner. CONCLUSIONS: Our work indicated that CPS1 is upregulated in LADC samples and that CPS1 might be used as a potential biomarker for the diagnostic and prognostic evaluation of LADC. Determining the detailed biological function of CPS1 in LADC tissues will provide promising and insightful information for our further study.

Treatment Strategy for Petroclival Meningiomas Based on a Proposed Classification in a Study of 168 Cases.

Petroclival meningiomas (PCMs) are regarded as one of the most formidable challenges in neurosurgery. We retrospectively assessed the surgical outcomes of PCMs based on a tumor classification to evaluate the long-term outcomes. A series of 168 patients with PCMs from July 1996 to January 2017. On the basis of the difference in the origin of dural attachment and patterns of growth, the PCMs were classified into 4 different types. The clinical characteristics, surgical record, and follow-up data of each type were reviewed. The study included 138 females (82.1%) with an average age of 49.9 ± 16.2 years. And 138 cases (82.1%) had developed neurological deficits preoperatively with the average tumor size of 44.0 ± 10.6 mm. Specific surgical approaches were applied depended on the tumor classification. Gross total resection (GTR) was achieved in 119 cases (70.8%) with the complications of 46 cases (27.7%). With a median follow-up of 86.5 months, there were 41 cases of recurrence/progress (25.7%) and 39 cases of morbidity (26.4%). Compared with the non-GTR group, the GTR significantly decreased the R/P rate (P = 0.001), prolonged the R/P-FS time (P = 0.032) and improved the follow-up neurological status (P = 0.026). Favorable outcomes and acceptable morbidity were achieved with the treatment strategy of the choice of specific approaches for each type. Meanwhile, the differences of each type in diverse clinical characteristic were verified. Individualized assessment and suitable approach choice should be based on the tumor classification to improved the GTR and quality of life for patients.

Photomultiplication type organic photodetectors based on electron tunneling injection.

Photomultiplication (PM) type organic photodetectors (OPDs) based on electron tunneling injection are achieved with a specific structure of ITO/ZnO/PC71BM:P3HT (100 : 5, wt/wt)/Au and can work well under forward and reverse bias. A rather low dark current density of the PM type OPDs is obtained due to the large electron injection barrier of 0.7 eV from the ITO electrode or 1.1 eV from the Au electrode, as well as the absence of continuous hole transport channels in the active layers. The external quantum efficiency (EQE) spectral shape of PM type OPDs can be easily adjusted by altering the bias polarity and active layer thickness, which can be well explained by the trapped hole distribution near the ITO and Au electrodes, respectively. The PM type OPDs with 400 nm active layers exhibit the maximum EQE of 3900% and 4900% under 5 V and -5 V bias, respectively. This work firstly achieves PM type OPDs with electron-only transport properties, which has great potential to well match with other organic electronic devices.

Photomultiplication Type Broad Response Organic Photodetectors with One Absorber Layer and One Multiplication Layer.

Broad response organic photodetectors (OPDs) with a photomultiplication (PM) effect are achieved with one absorber layer and one multiplication layer. The response range of the PM-OPDs is primarily determined by materials in the absorber layer, and the external quantum efficiency (EQE) of the PM-OPDs is mainly controlled by the multiplication layer. Here, double-layered PM-OPDs were designed with an ITO/ZnO/PM6:Y6/PC71BM:P3HT (100:5, w/w)/Au structure, where PM6:Y6 is employed as an absorber layer and PC71BM:P3HT is used as a multiplication layer. The optimal PM-OPDs exhibit a broad response covering 350-950 nm. Meanwhile, the optimal PM-OPDs exhibit the largest EQE value of ∼1200% and a maximum specific detectivity (D*) of ∼6.8 × 10-12 cm Hz1/2 W-1 under a 10 V bias. This double-layered approach may be a smart strategy for realizing PM-OPDs with an easily adjustable response range.

Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma via Upregulating the FUS/MDM2 Ubiquitination Axis.

BACKGROUND: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. METHODS: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. RESULTS: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. Subsequent investigations indicated that reduced expression of ADAMTS9-AS2 significantly suppressed expression of the FUS protein, which was predicted as a direct substrate of ADAMTS9-AS2. Expression trends of FUS were directly correlated with those of ADAMTS9-AS2, as shown by increasing concentrations and prolonged treatment with TMZ. RNA pull-down and RIP assays indicated that both endogenous and exogenous ADAMTS9-AS2 directly binds to the RRM and Znf_RanBP2 domains of FUS, consequently increasing FUS protein expression. Knockdown of ADAMTS9-AS2 reduced the half-life of FUS and decreased FUS protein stability via K48 ubiquitin degradation. Moreover, the E3 ubiquitin-protein ligase MDM2 interacts with and down regulates FUS, while the RRM and Znf_RanBP2 domains of FUS facilitate its binding with MDM2. ADAMTS9-AS2 decreased the interaction between MDM2 and FUS, which mediates FUS K48 ubiquitination. Additionally, knockdown of the ADAMTS9-AS2/FUS signaling axis significantly alleviated progression and metastasis in TMZ-resistant cells. CONCLUSION: ADAMTS9-AS2 possessed a novel function that promotes TMZ resistance via upregulating the FUS/MDM2 axis in GBM cells. The RRM or Znf_RanBP2 domains of FUS facilitate the combination of ADAMTS9-AS2 and FUS, competitively inhibiting MDM2-dependent FUS K48 ubiquitination and resulting in enhanced FUS stability and TMZ resistance. Our results suggest that the ADAMTS9-AS2/FUS/MDM2 axis may represent a suitable prognostic biomarker and a potential target in TMZ-resistant GBM therapy.