Superhalide-Anion-Motivator Reforming-Enabled Bipolar Manipulation toward Longevous Energy-Type Zn||Chalcogen Batteries.

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

Preoperative Discrimination of CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase-Mutant Astrocytoma: A Deep Learning-Based Radiomics Model Using MRI.

BACKGROUND: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion has been verified as an independent and critical biomarker of negative prognosis and short survival in isocitrate dehydrogenase (IDH)-mutant astrocytoma. Therefore, noninvasive and accurate discrimination of CDKN2A/B homozygous deletion status is essential for the clinical management of IDH-mutant astrocytoma patients. PURPOSE: To develop a noninvasive, robust preoperative model based on MR image features for discriminating CDKN2A/B homozygous deletion status of IDH-mutant astrocytoma. STUDY TYPE: Retrospective. POPULATION: Two hundred fifty-one patients: 107 patients with CDKN2A/B homozygous deletion and 144 patients without CDKN2A/B homozygous deletion. FIELD STRENGTH/SEQUENCE: 3.0 T/1.5 T: Contrast-enhanced T1-weighted spin-echo inversion recovery sequence (CE-T1WI) and T2-weighted fluid-attenuation spin-echo inversion recovery sequence (T2FLAIR). ASSESSMENT: A total of 1106 radiomics and 1000 deep learning features extracted from CE-T1WI and T2FLAIR were used to develop models to discriminate the CDKN2A/B homozygous deletion status. Radiomics models, deep learning-based radiomics (DLR) models and the final integrated model combining radiomics features with deep learning features were developed and compared their preoperative discrimination performance. STATISTICAL TESTING: Pearson chi-square test and Mann Whitney U test were used for assessing the statistical differences in patients' clinical characteristics. The Delong test compared the statistical differences of receiver operating characteristic (ROC) curves and area under the curve (AUC) of different models. The significance threshold is P < 0.05. RESULTS: The final combined model (training AUC = 0.966; validation AUC = 0.935; test group: AUC = 0.943) outperformed the optimal models based on only radiomics or DLR features (training: AUC = 0.916 and 0.952; validation: AUC = 0.886 and 0.912; test group: AUC = 0.862 and 0.902). DATA CONCLUSION: Whether based on a single sequence or a combination of two sequences, radiomics and DLR models have achieved promising performance in assessing CDKN2A/B homozygous deletion status. However, the final model combining both deep learning and radiomics features from CE-T1WI and T2FLAIR outperformed the optimal radiomics or DLR model. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

A novel MRI-based deep learning networks combined with attention mechanism for predicting CDKN2A/B homozygous deletion status in IDH-mutant astrocytoma.

OBJECTIVES: To develop a high-accuracy MRI-based deep learning method for predicting cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion status in isocitrate dehydrogenase (IDH)-mutant astrocytoma. METHODS: Multiparametric brain MRI data and corresponding genomic information of 234 subjects (111 positives for CDKN2A/B homozygous deletion and 123 negatives for CDKN2A/B homozygous deletion) were obtained from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) respectively. Two independent multi-sequence networks (ResFN-Net and FN-Net) are built on the basis of ResNet and ConvNeXt network combined with attention mechanism to classify CDKN2A/B homozygous deletion status using MR images including contrast-enhanced T1-weighted imaging (CE-T1WI) and T2-weighted imaging (T2WI). The performance of the network is summarized by three-way cross-validation; ROC analysis is also performed. RESULTS: The average cross-validation accuracy (ACC) of ResFN-Net is 0.813. The average cross-validation area under curve (AUC) of ResFN-Net is 0.8804. The average cross-validation ACC and AUC of FN-Net is 0.9236 and 0.9704, respectively. Comparing all sequence combinations of the two networks (ResFN-Net and FN-Net), the sequence combination of CE-T1WI and T2WI performed the best, and the ACC and AUC were 0.8244, 0.8975 and 0.8971, 0.9574, respectively. CONCLUSIONS: The FN-Net deep learning networks based on ConvNeXt network achieved promising performance for predicting CDKN2A/B homozygous deletion status of IDH-mutant astrocytoma. CLINICAL RELEVANCE STATEMENT: A novel deep learning network (FN-Net) based on preoperative MRI was developed to predict the CDKN2A/B homozygous deletion status. This network has the potential to be a practical tool for the noninvasive characterization of CDKN2A/B in glioma to support personalized classification and treatment planning. KEY POINTS: • CDKN2A/B homozygous deletion status is an important marker for glioma grading and prognosis. • An MRI-based deep learning approach was developed to predict CDKN2A/B homozygous deletion status. • The predictive performance based on ConvNeXt network was better than that of ResNet network.

Dynamically Ion-Coordinated Bipolar Organodichalcogenide Cathodes Enabling High-Energy and Durable Aqueous Zn Batteries.

Bipolar organic cathode materials (OCMs) implementing cation/anion storage mechanisms are promising for high-energy aqueous Zn batteries (AZBs). However, conventional organic functional group active sites in OCMs usually fail to sufficiently unlock the high-voltage/capacity merits. Herein, we initially report dynamically ion-coordinated bipolar OCMs as cathodes with chalcogen active sites to solve this issue. Unlike conventional organic functional groups, chalcogens bonded with conjugated group undergo multielectron-involved positive-valence oxidation and negative-valence reduction, affording higher redox potentials and reversible capacities. With phenyl diselenide (PhSe-SePh, PDSe) as a proof of concept, it exhibits a conversion pathway from (PhSe)- to (PhSe-SePh)0 and then to (PhSe)+ as unveiled by characterization and theoretical simulation, where the diselenide bonds are periodically broken and healed, dynamically coordinating with ions (Zn2+ and OTF-). When confined into ordered mesoporous carbon (CMK-3), the dissolution of PDSe intermediates is greatly inhibited to obtain an ultralong lifespan without voltage/capacity compromise. The PDSe/CMK-3 || Zn batteries display high reversibility capacity (621.4 mAh gPDSe -1), distinct discharge plateau (up to 1.4 V), high energy density (578.3 Wh kgPDSe -1), and ultralong lifespan (12 000 cycles) at 10 A g-1, far outperforming conventional bipolar OCMs. This work sheds new light on conversion-type active site engineering for high-voltage/capacity bipolar OCMs towards high-energy AZBs.

Pyrrolic-Nitrogen Chemistry in 1-(2-hydroxyethyl)imidazole Electrolyte Additives toward a 50,000-Cycle-Life Aqueous Zinc-Iodine Battery.

Rechargeable aqueous zinc iodine (Zn-I2) batteries offer benefits such as low cost and high safety. Nevertheless, their commercial application is hindered by hydrogen evolution reaction (HER) and polyiodide shuttle, which result in a short lifespan. In this study, 1-(2-hydroxyethyl)imidazole (HEI) organic molecules featuring pyrrole-N groups are introduced as dually-functional electrolyte additives to simultaneously stabilize Zn anode and confine polyiodide through ion-dipole interactions. The pyrrole-N groups in HEI can preserve the interfacial pH equilibrium at Zn anode by reversibly capturing H+ ions and dynamically neutralizing OH- ions, thereby suppressing the HER. Notably, the H2 evolution rate at the Zn anode is reduced to a mere 2.20 µmol h-1 cm-2. Furthermore, the pyrrole-N moieties in HEI effectively curtail the polyiodide shuttle at I2 cathode, which show adsorption energies of -0.174 eV for I2, -0.521 eV for I3-, and -0.768 eV for I-, as indicated by density functional theory calculations. Electrochemical testing demonstrates that the Zn//Zn symmetric cell maintains stable cycling for up to 4,200 hours at 1 mA cm-2. Most strikingly, at a high I2 mass loading of 9.7 mg cm-2, the Zn-I2 battery achieves an extraordinary cycle life of 50,000 cycles.

Stabilizing Zn/electrolyte Interphasial Chemistry by a Sustained-Release Drug Inspired Indium-Chelated Resin Protective Layer for High-Areal-Capacity Zn//V2O5 Batteries.

For zinc-metal batteries, the instable chemistry at Zn/electrolyte interphasial region results in severe hydrogen evolution reaction (HER) and dendrite growth, significantly impairing Zn anode reversibility. Moreover, an often-overlooked aspect is this instability can be further exacerbated by the interaction with dissolved cathode species in full batteries. Here, inspired by sustained-release drug technology, an indium-chelated resin protective layer (Chelex-In), incorporating a sustained-release mechanism for indium, is developed on Zn surface, stabilizing the anode/electrolyte interphase to ensure reversible Zn plating/stripping performance throughout the entire lifespan of Zn//V2O5 batteries. The sustained-release indium onto Zn electrode promotes a persistent anticatalytic effect against HER and fosters uniform heterogeneous Zn nucleation. Meanwhile, on the electrolyte side, the residual resin matrix with immobilized iminodiacetates anions can also repel detrimental anions (SO4 2- and polyoxovanadate ions dissolved from V2O5 cathode) outside the electric double layer. This dual synergetic regulation on both electrode and electrolyte sides culminates a more stable interphasial environment, effectively enhancing Zn anode reversibility in practical high-areal-capacity full battery systems. Consequently, the bio-inspired Chelex-In protective layer enables an ultralong lifespan of Zn anode over 2800 h, which is also successfully demonstrated in ultrahigh areal capacity Zn//V2O5 full batteries (4.79 mAh cm-2).

Hydrophobic Ion Barrier-Enabled Ultradurable Zn (002) Plane Orientation towards Long-Life Anode-Less Zn Batteries.

Gradual disability of Zn anode and high negative/positive electrode (N/P) ratio usually depreciate calendar life and energy density of aqueous Zn batteries (AZBs). Herein, within original Zn2+-free hydrated electrolytes, a steric hindrance/electric field shielding-driven "hydrophobic ion barrier" is engineered towards ultradurable (002) plane-exposed Zn stripping/plating to solve this issue. Guided by theoretical simulations, hydrophobic adiponitrile (ADN) is employed as a steric hindrance agent to ally with inert electric field shielding additive (Mn2+) for plane adsorption priority manipulation, thereby constructing the "hydrophobic ion barrier". This design robustly suppresses the (002) plane/dendrite growth, enabling ultradurable (002) plane-exposed dendrite-free Zn stripping/plating. Even being cycled in Zn‖Zn symmetric cell over 2150 h at 0.5 mA cm-2, the efficacy remains well-kept. Additionally, Zn‖Zn symmetric cells can be also stably cycled over 918 h at 1 mA cm-2, verifying uncompromised Zn stripping/plating kinetics. As-assembled anode-less Zn‖VOPO4 ⋅ 2H2O full cells with a low N/P ratio (2 : 1) show a high energy density of 75.2 Wh kg-1 full electrode after 842 cycles at 1 A g-1, far surpassing counterparts with thick Zn anode and low cathode loading mass, featuring excellent practicality. This study opens a new avenue by robust "hydrophobic ion barrier" design to develop long-life anode-less Zn batteries.

Molecular Bridging Induced Anti-salting-out Effect Enabling High Ionic Conductive ZnSO4-based Hydrogel for Quasi-solid-state Zinc Ion Batteries.

Hydrogel electrolytes (HEs) hold great promise in tackling severe issues emerging in aqueous zinc-ion batteries, but the prevalent salting-out effect of kosmotropic salt causes low ionic conductivity and electrochemical instability. Herein, a subtle molecular bridging strategy is proposed to enhance the compatibility between PVA and ZnSO4 from the perspective of hydrogen-bonding microenvironment re-construction. By introducing urea containing both an H-bond acceptor and donor, the broken H-bonds between PVA and H2O, initiated by the SO42--driven H2O polarization, could be re-united via intense intermolecular hydrogen bonds, thus leading to greatly increased carrying capacity of ZnSO4. The urea-modified PVA-ZnSO4 HEs featuring a high ionic conductivity up to 31.2 mS cm-1 successfully solves the sluggish ionic transport dilemma at the solid-solid interface. Moreover, an organic solid-electrolyte-interphase can be derived from the in-situ electro-polymerization of urea to prohibit H2O-involved side reactions, thereby prominently improving the reversibility of Zn chemistry. Consequently, Zn anodes witness an impressive lifespan extension from 50 h to 2200 h at 0.1 mA cm-2 while the Zn-I2 full battery maintains a remarkable Coulombic efficiency (>99.7%) even after 8000 cycles. The anti-salting-out strategy proposed in this work provides an insightful concept for addressing the phase separation issue of functional HEs.

Multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI predict ATRX mutation status in IDH-mutant lower-grade gliomas.

OBJECTIVES: To develop a clinical radiomics-integrated model based on 18 F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and multi-modal MRI for predicting alpha thalassemia/mental retardation X-linked (ATRX) mutation status of IDH-mutant lower-grade gliomas (LGGs). METHODS: One hundred and two patients (47 ATRX mutant-type, 55 ATRX wild-type) diagnosed with IDH-mutant LGGs (CNS WHO grades 1 and 2) were retrospectively enrolled. A total of 5540 radiomics features were extracted from structural MR (sMR) images (contrast-enhanced T1-weighted imaging, CE-T1WI; T2-weighted imaging, and T2WI), functional MR (fMR) images (apparent diffusion coefficient, ADC; cerebral blood volume, CBV), and metabolic PET images ([18F]FDG PET). The random forest algorithm was used to establish a clinical radiomics-integrated model, integrating the optimal multi-modal radiomics model with three clinical parameters. The predictive effectiveness of the models was evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA). RESULTS: The optimal multi-modal model incorporated sMR (CE-T1WI), fMR (ADC), and metabolic ([18F]FDG) images ([18F]FDG PET+ADC+ CE-T1WI) with the area under curves (AUCs) in the training and test groups of 0.971 and 0.962, respectively. The clinical radiomics-integrated model, incorporating [18F]FDG PET+ADC+CE-T1WI, three clinical parameters (KPS, SFSD, and ATGR), showed the best predictive effectiveness in the training and test groups (0.987 and 0.975, respectively). CONCLUSIONS: The clinical radiomics-integrated model with metabolic, structural, and functional information based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting the ATRX mutation status of IDH-mutant LGGs. KEY POINTS: • The clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting ATRX mutation status in LGGs. • The study investigated the value of multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI in LGGs regarding ATRX mutation status prediction. • The integrated model provided structural, functional, and metabolic information simultaneously and demonstrated with satisfactory calibration and discrimination in the training and test groups (0.987 and 0.975, respectively).

Lithium Bis(oxalate)borate Additive for Self-repairing Zincophilic Solid Electrolyte Interphases towards Ultrahigh-rate and Ultra-stable Zinc Anodes.

The artificial solid electrolyte interphase (SEI) plays a pivotal role in Zn anode stabilization but its long-term effectiveness at high rates is still challenged. Herein, to achieve superior long-life and high-rate Zn anode, an exquisite electrolyte additive, lithium bis(oxalate)borate (LiBOB), is proposed to in situ derive a highly Zn2+ -conductive SEI and to dynamically patrol its cycling-initiated defects. Profiting from the as-constructed real-time, automatic SEI repairing mechanism, the Zn anode can be cycled with distinct reversibility over 1800 h at an ultrahigh current density of 50 mA cm-2 , presenting a record-high cumulative capacity up to 45 Ah cm-2 . The superiority of the formulated electrolyte is further demonstrated in the Zn||MnO2 and Zn||NaV3 O8 full batteries, even when tested under harsh conditions (limited Zn supply (N/P≈3), 2500 cycles). This work brings inspiration for developing fast-charging Zn batteries toward grid-scale storage of renewable energy sources.

Hydrated Eutectic Electrolytes Stabilizing Quasi-Underpotential Mg Plating/Stripping for High-Voltage Mg Batteries.

Aqueous rechargeable Mg batteries (ARMBs) usually fail from severe anode passivation, alternatively, executing quasi-underpotential Mg plating/stripping chemistry (UPMC) on a proper heterogeneous metal substrate is a crucial remedy. Herein, a stable UPMC on Zn substrate is initially achieved in new hydrated eutectic electrolytes (HEEs), delivering an ultralow UPMC overpotential and high energy/voltage plateau of ARMBs. The unique eutectic property remarkably expands the lower limit of electrochemical stability window (ESW) of HEEs and undermines the competition between hydrogen evolution/corrosion reactions and UPMC, enabling a reversible UPMC. The UPMC is carefully revealed by multiple characterizations, which shows a low overpotential of 50 mV at 0.1 mA cm-2 over 550 h. With sulfonic acid-doped polyaniline (SPANI) cathodes, UPMC-based full cells show high energy/power densities of 168.6 Wh kg-1 /2.1 kWh kg-1 and voltage plateau of 1.3 V, far overwhelming conventional aqueous systems.

Manipulating OH- -Mediated Anode-Cathode Cross-Communication Toward Long-Life Aqueous Zinc-Vanadium Batteries.

The anode-cathode interplay is an important but rarely considered factor that initiates the degradation of aqueous zinc ion batteries (AZIBs). Herein, to address the limited cyclability issue of V-based AZIBs, Al2 (SO4 )3 is proposed as decent electrolyte additive to manipulate OH- -mediated cross-communication between Zn anode and NaV3 O8 ⋅ 1.5H2 O (NVO) cathode. The hydrolysis of Al3+ creates a pH≈0.9 strong acidic environment, which unexpectedly prolongs the anode lifespan from 200 to 1000 h. Such impressive improvement is assigned to the alleviation of interfacial OH- accumulation by Al3+ adsorption and solid electrolyte interphase formation. Accordingly, the strongly acidified electrolyte, associated with the sedated crossover of anodic OH- toward NVO, remarkably mitigate its undesired dissolution and phase transition. The interrupted OH- -mediated communication between the two electrodes endows Zn||NVO batteries with superb cycling stability, at both low and high scan rates.

Effects of CYP2C19, CYP2C9 and CYP3A4 gene polymorphisms on plasma voriconazole levels in Chinese pediatric patients.

OBJECTIVES: Voriconazole is the most commonly used antifungal agent in clinical application. Previous studies suggested that voriconazole was extensively metabolized by CYP450 enzyme system, including CYP2C19, CYP2C9 and CYP3A4, which contributed to the individual variability of the pharmacokinetic process of voriconazole. This study aimed to investigate the effects of CYP2C19, CYP2C9 and CYP3A4 gene polymorphisms on plasma voriconazole concentrations in Chinese pediatric patients. METHODS: This study prospectively evaluated pediatric patients administrating voriconazole for the treatment or prophylaxis of invasive fungal infections from October 2018 to July 2020. Seven single-nucleotide polymorphisms in CYP2C19 (CYP2C19*2, CYP2C19*3, and CYP2C19*17), CYP2C9 (CYP2C9*3, CYP2C9*13) and CYP3A4 (CYP3A4*22, rs4646437) were detected by real-time fluorescent PCR with TaqMan probes. The voriconazole trough plasma concentration was determined by UPLC-MS/MS. RESULTS: A total of 68 pediatric patients were enrolled in this study. Our results showed that voriconazole plasma concentrations of patients with CYP2C19*2 or CYP2C19*3 allele were significantly higher than that with wild-type carriers (P < 0.0001, P = 0.004, respectively). However, CYP2C9*3 and CYP3A4 rs4646437 were not significantly associated with voriconazole plasma levels. The CYP2C19*17, CYP2C9*13 and CYP3A4*22 alleles were not observed in our study. Additionally, multiple linear regression analysis indicated that CYP2C19*2 and CYP2C19*3 alleles remained predictors of voriconazole plasma concentration (r2 = 0.428; P < 0.0001). For CYP2C19 metabolizer phenotype, trough concentration of voriconazole was significantly lower in NM group compared with IM (P < 0.0001) and PM (P = 0.004) groups. CONCLUSION: Voriconazole plasma levels in pediatric patients are mainly affected by CYP2C19 gene polymorphisms.

UPLC-MS/MS method for the determination of voriconazole plasma concentration from pediatric patients with hematologic tumors: An application toward personalized therapy.

Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first-line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000-5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C18 column with the gradient mobile phases comprising 0.1% methanoic acid in acetonitrile (A) and 0.1% methanoic acid in water (B). In the selective reaction monitor mode, the mass spectrometric detection was carried out using an TSQ Endura triple quadruple mass spectrometer. The performance of this UPLC-MS/MS method was validated as per the National Medical Products Administration for Bioanalytical Method Validation. Additionally, the plasma concentrations of VOR in pediatric patients with hematologic tumors were detected using this method, and the analyzed results were used for personalized therapy.

Ten Thousand-Cycle Ultrafast Energy Storage of Wadsley-Roth Phase Fe-Nb Oxides with a Desolvation Promoting Interfacial Layer.

Developing advanced electrode materials with enhanced charge-transfer kinetics is the key to realizing fast energy storage technologies. Commonly used modification strategies, such as nanoengineering and carbon coating, are mainly focused on electron transfer and bulk Li+ diffusion. Nonetheless, the desolvation behavior, which is considered as the rate-limiting process for charge-storage, is rarely studied. Herein, we designed a nitridation layer on the surface of Wadsley-Roth phase FeNb11O29 (FNO-x@N) to act as a desolvation promoter. Theoretical calculations demonstrate that the adsorption and desolvation of solvated Li+ is efficiently improved at FNO-x@N/electrolyte interphase, leading to the reduced desolvation energy barrier. Moreover, the nitridation layer can also help to prevent solvent cointercalation during Li+ insertion, leading to advantageous shrinkage of block area and reduced volume change of lattice cell during cycling. Consequently, FNO-x@N exhibits a high-rate capacity of 129.7 mAh g-1 with negligible capacity decay for 10 000 cycles.

Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.

Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87-MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down-regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual-luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at -236 to -230 bp and -1354 to -1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells.

Usefulness of preoperative coronary computed tomography angiography in high risk non-cardiovascular surgery old patients with unknown or suspected coronary artery disease.

BACKGROUND: Cumulative evidence has shown that the non-invasive modality of coronary computed tomography angiography (CCTA) has evolved as an alternative to invasive coronary angiography, which can be used to quantify plaque burden and stenosis and identify vulnerable plaque, assisting in diagnosis, prognosis and treatment. With the increasing elderly population, many patients scheduled for non-cardiovascular surgery may have concomitant coronary artery disease (CAD). The aim of this study was to investigate the usefulness of preoperative CCTA to rule out or detect significant CAD in this cohort of patients and the impact of CCTA results to clinical decision-making. METHODS: 841 older patients (age 69.5 ± 5.8 years, 74.6% males) with high risk non-cardiovascular surgery including 771 patients with unknown CAD and 70 patients with suspected CAD who underwent preoperative CCTA were retrospectively enrolled. Multivariate logistic regression analysis was performed to determine predictors of significant CAD and the event of cancelling scheduled surgery in patients with significant CAD. RESULTS: 677 (80.5%) patients had non-significant CAD and 164 (19.5%) patients had significant CAD. Single-, 2-, and 3- vessel disease was found in 103 (12.2%), 45 (5.4%) and 16 (1.9%) patients, respectively. Multivariate analysis demonstrated that positive ECG analysis and Agatston score were independently associated with significant CAD, and the optimal cutoff of Agatston score was 195.9. The event of cancelling scheduled surgery was increased consistently according to the severity of stenosis and number of obstructive major coronary artery. Multivariate analysis showed that the degree of stenosis was the only independent predictor for cancelling scheduled surgery. In addition, medication using at perioperative period increased consistently according to the severity of stenosis. CONCLUSIONS: In older patients referred for high risk non-cardiovascular surgery, preoperative CCTA was useful to rule out or detect significant CAD and subsequently influence patient disposal. However, it might be unnecessary for patients with negative ECG and low Agatston score. Trial registration Retrospectively registered.

SCN1A and SCN2A polymorphisms are associated with response to valproic acid in Chinese epilepsy patients.

PURPOSE: There is a large inter-individual variation in the efficacy of valproic acid (VPA) against epilepsy. The genetic polymorphism influence of sodium channels on VPA response remains a matter of debate. The aim of the study was to explore the effect of SCN1A and SCN2A gene polymorphisms on VPA response in the treatment of epilepsy among Chinese patients. METHODS: A total of 354 epileptic patients with VPA treatment were genotyped for five single nucleotide polymorphisms (SNP), including SCN1A rs10188577 T>C, rs2298771 T>C, rs3812718 G>A, and SCN2A rs2304016 A>G, rs17183814 G>A. A binary logistic regression analysis was performed to evaluate the association of genotype with VPA antiepileptic effects, adjusting the influence of confounding factors. RESULTS: Genotype distributions of all selected SNPs were consistent with the Hardy-Weinberg equilibrium in epilepsy patients. SCN1A rs3812718 and SCN2A rs2304016 were found to be significantly associated with VPA response, both in monotherapy and in VPA-based polytherapy. Patients with the rs3812718 A allele were more frequently seen in the VPA-responsive group (P < 0.05), and the rs2304016 G allele was related to an increased risk of resistance to VPA therapy (P < 0.05). CONCLUSIONS: Our study revealed that SCN1A rs3812718 and SCN2A rs2304016 polymorphisms might be markers of VPA response in Chinese epilepsy patients. TRIAL REGISTRATION: ChiCTR-1800016477.

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas.

BACKGROUND/AIMS: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). METHODS: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. RESULTS: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient' survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. CONCLUSION: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.