High Expression of KIFC1 in Glioma Correlates with Poor Prognosis.

OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

Ti3C2Tx/laser-induced graphene-based micro-droplet electrochemical sensing platform for rapid and sensitive detection of benomyl.

The design and fabrication of high-performance electrode devices are highly important for the practical application of electrochemical sensors. In this study, flexible three-dimensional porous graphene electrode devices were first facilely fabricated using common laser ablation technique at room temperature. After then, hydrophilic two-dimensional MXene (Ti3C2Tx) nanosheet was decorated on the surface of the laser-induced graphene (LIG), resulting in disposable Ti3C2Tx/LIG electrode devices. After introducing Ti3C2Tx nanosheet, the electrochemical active area, electron transfer ability of LIG electrode device and its adsorption efficiency toward organic pesticide benomyl was significantly boosted. As a result, the fabricated Ti3C2Tx/LIG electrode device exhibited significantly enhanced electrocatalytic activity toward benomyl oxidation. Based on this, a novel and ultra-sensitive electrochemical platform for micro-droplet detection of benomyl was achieved in the range of 10 nM-6000 nM with detection sensitivity of 169.9 µA µM-1 cm-2 and detection limit of 5.8 nM. Considering the low-cost Ti3C2Tx/LIG electrode devices are rarely used for electrochemical analysis, we believed this research work will contribute to exploring the broader application of MXene/LIG electrode devices in the field of electrochemical sensing.

Hierarchical Carbon Network Composites Derived from ZIF-8 for High-Efficiency Microwave Absorption.

Metal-organic framework (MOF)-derived composites have gained wide attention due to their specific structures and enhanced performance. In this work, we prepared carbon nanotubes with Fe nanoparticles connected to two-dimensional (2D) hierarchical carbon network composites via a low-pressure gas-solid reaction strategy. Specifically, the three-dimensional (3D) networks derived from ZIF-8 exploited the carbon nanotubes with the function of charge modulation. Meanwhile, we utilized the interconnected 2D nanostructures to optimize impedance matching and facilitate multiple scattering, ultimately improving the overall microwave absorption performance. Furthermore, based on the well-designed structures, the composites prepared at 800 °C (Fe-N-C@CNTs-800) achieved the best reflection loss (RL) of -58.5 dB, thereby obtaining superior microwave absorption performance. Overall, this study provides a good groundwork for further investigation into the modification and dimension design of novel hierarchical microwave absorbers.

A novel approach on designing ultrahigh burnup metallic TWR fuels: Upsetting the current technological limits.

Abstract: The grand challenge of "net-zero carbon" emission calls for technological breakthroughs in energy production. The traveling wave reactor (TWR) is designed to provide economical and safe nuclear power and solve imminent problems, including limited uranium resources and radiotoxicity burdens from back-end fuel reprocessing/disposal. However, qualification of fuels and materials for TWR remains challenging and it sets an "end of the road" mark on the route of R&D of this technology. In this article, a novel approach is proposed to maneuver reactor operations and utilize high-temperature transients to mitigate the challenges raised by envisioned TWR service environment. Annular U-50Zr fuel and oxidation dispersion strengthened (ODS) steels are proposed to be used instead of the current U-10Zr and HT-9 ferritic/martensitic steels. In addition, irradiation-accelerated transport of Mn and Cr to the cladding surface to form a protective oxide layer as a self-repairing mechanism was discovered and is believed capable of mitigating long-term corrosion. This work represents an attempt to disruptively overcome current technological limits in the TWR fuels. Impact statement: After the Fukushima accident in 2011, the entire nuclear industry calls for a major technological breakthrough that addresses the following three fundamental issues: (1) Reducing spent nuclear fuel reprocessing demands, (2) reducing the probability of a severe accident, and (3) reducing the energy production cost per kilowatt-hour. An inherently safe and ultralong life fast neutron reactor fuel form can be such one stone that kills the three birds. In light of the recent development findings on U-50Zr fuels, we hereby propose a disruptive, conceptual metallic fuel design that can serve the following purposes at the same time: (1) Reaching ultrahigh burnup of above 40% FIMA, (2) possessing strong inherent safety features, and (3) extending current limits on fast neutron irradiation dose to be far beyond 200 dpa. We believe that this technology will be able to bring about revolutionary changes to the nuclear industry by significantly lowering the operational costs as well as improving the reactor system safety to a large extent. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-022-00420-4.

Colossal Anomalous Hall Effect in Ferromagnetic van der Waals CrTe2.

van der Waals crystals exhibit excellent material performance when exfoliated to few-atomic-layer thickness. In contrast, the van der Waals thin films more than 10 nm thick are believed to show bulk properties, in which outstanding material performance is rarely found. Here we report the largest anomalous Hall conductivity observed so far in a 170 nm van der Waals ferromagnetic 1T-CrTe2 flake, which reaches 67,000 Ω-1 cm-1. Such a colossal anomalous Hall conductivity in 1T-CrTe2 is dominated by the extrinsic skew scattering process rather than the intrinsic Berry phase effect, as evidenced by the linear relation between the anomalous Hall conductivity and the longitudinal conductivity. Defying the dilemma of mutually exclusive large anomalous Hall angle and high electric conductivity for most ferromagnets, 1T-CrTe2 achieves both in a thin film sample. Considering the shared physics of the anomalous Hall effect and the spin Hall effect, our finding offers a guideline for searching large spin Hall materials of high conductivity which may overcome the bottleneck of overheating in spintronics devices.

Field-Free Deterministic Magnetization Switching Induced by Interlaced Spin-Orbit Torques.

Spin-orbit torque (SOT) magnetic random access memory is envisioned as an emerging nonvolatile memory due to its ultrahigh speed and low power consumption. The field-free switching scheme in SOT devices is of great interest to both academia and industry. Here, we propose a novel field-free deterministic magnetization switching scheme in a regular magnetic tunnel junction by using two currents sequentially passing interlaced paths, with less requirements of the manufacturing process or additional physical effects. The switching is bipolar since the final magnetization state depends on the combination of current paths. The functionality and robustness of the proposed scheme are validated through both macrospin and micromagnetic simulation. The influences of field-like torque and the Dzyaloshinskii-Moriya interaction effect are further researched. Our proposed scheme shows good scalability and is expected to realize novel digital logic and even computing-in-memory platforms.

Artesunate ameliorates sepsis-induced acute lung injury by activating the mTOR/AKT/PI3K axis.

Sepsis-induced acute lung injury (ALI) remains one of the most common disorders in hospitals. The aim of this research was to explore the underlying characteristics and mechanisms of artesunate (AS) in protecting rat lungs from sepsis. The sepsis-induced ALI model was generated in SD rats by the intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. The rats were randomly assigned into 4 groups: Sham, LPS, LPS + AS, and LPS + AS + LY294002. Pathological evaluation of the lungs was conducted by HE staining, immunofluorescence, and TUNEL assay, and the MPO activity and the W/D ratio of each group were evaluated. The levels of inflammatory mediators (TNF-α and IL-6) were measured by immunoblotting, immunofluorescence and real-time PCR. Western blotting was used to determine the protein levels of PI3K, cleaved Caspase-3, p-mTOR, mTOR, p-Akt, and Akt in the lungs. The MPO activity, W/D ratio and lung injury score were obviously elevated after induction of ALI by LPS. Nevertheless, these alterations could be inhibited by AS. In addition, sepsis decreased the levels of p-mTOR, p-Akt, and PI3K and elevated the expression of cl-caspase-3, TNF-α, and IL-6 in the lungs. After AS administration, these alterations were obviously decreased, but treatment with the PI3K antagonist LY294002 inhibited the function of AS. AS could partially protect against LPS-induced ALI by inhibiting apoptosis and inflammatory mediator production, and this function is perhaps associated with the regulation of the mTOR/AKT/PI3K axis. These findings suggest that AS may possess certain beneficial characteristics in protecting the lungs from sepsis.

Magnetization Dynamics Modulated by Dzyaloshinskii-Moriya Interaction in the Double-Interface Spin-Transfer Torque Magnetic Tunnel Junction.

Currently double-interface magnetic tunnel junctions (MTJs) have been developed for enhancing the thermal stability barrier at the nanoscale technology node. Dzyaloshinskii-Moriya interaction (DMI) inevitably exists in such devices due to the use of the heavy-metal/ferromagnet structures. Previous studies have demonstrated the detrimental effect of DMI on the conventional single-interface spin-transfer torque (STT) MTJs. Here, in this work, we will prove that the detrimental effect of DMI could be almost eliminated in the double-interface STT-MTJ. This conclusion is attributed to the suppressing effect of Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction on the DMI. Detailed mechanisms are analyzed based on the theoretical models and micromagnetic simulation results. Our work highlights the importance of appropriately controlling the DMI in the composite free layer of the double-interface STT-MTJ.

Field-free spin-orbit-torque switching of perpendicular magnetization aided by uniaxial shape anisotropy.

It has been demonstrated that the switching of perpendicular magnetization can be achieved with spin-orbit torque (SOT) at an ultrafast speed and low energy consumption. However, to make the switching deterministic, an undesirable magnetic field or unconventional device geometry is required to break the structure inverse symmetry. Here we propose a novel scheme for SOT-induced field-free deterministic switching of perpendicular magnetization. The proposed scheme can be implemented in a simple magnetic tunnel junction (MTJ)/heavy-metal system, without the need of complicated device structure. The perpendicular-anisotropy MTJ is patterned into elliptical shape and misaligned with the axis of the heavy metal, so that the uniaxial shape anisotropy aids the magnetization switching. Furthermore, unlike the conventional switching scheme where the switched final magnetization state is dependent on the direction of the applied current, in our scheme the bipolar switching is implemented by choosing different current paths, which offers a new freedom for developing novel spintronics memories or logic devices. Through the macrospin simulation, we show that a wide operation window of the applied current pulse can be obtained in the proposed scheme. The precise control of pulse amplitude or pulse duration is not required. The influences of key parameters such as damping constant and field-like torque strength are discussed as well.

Golgi phosphoprotein 3 sensitizes the tumour suppression effect of gefitinib on gliomas.

OBJECTIVES: We previously reported that Golgi phosphoprotein 3 (GOLPH3) promotes glioma progression by inhibiting EGFR endocytosis and degradation, leading to EGFR accumulation and PI3K-AKT pathway over-activation. In the current study, we examine whether GOLPH3 affects the response of glioma cells to gefitinib, an EGFR selective inhibitor. MATERIALS AND METHODS: The expression of GOLPH3 and EGFR in glioma cells was detected by immunofluorescence and immunoblotting. The cell viability or growth in vitro was determined by CCK-8, EdU incorporation and clonogenic assays. The primary glioma cells were cultured by trypsin and mechanical digestion. The transwell invasion assay was used to examine the primary glioma cell motility. Intracranial glioma model in nude mice were established to explore the sensitivity of gefitinib to GOLPH3 high cancer cells in vivo. RESULTS: Both the immortalized and primary glioma cells with GOLPH3 over-expression hold higher EGFR protein levels on the cell membrane and exhibited higher sensitivity to gefitinib. In addition, primary glioma cells with higher GOLPH3 level exhibited stronger proliferation behaviour. Importantly, GOLPH3 enhanced the anti-tumour effect of gefitinib in vivo. Consistently, after gefitinib treatment, tumours derived from GOLPH3 over-expression cells exhibited lower Ki67-positive and higher cleaved caspase-3-positive cells than control tumours. CONCLUSIONS: Our results demonstrate that GOLPH3 increases the sensitivity of glioma cells to gefitinib. Our study provides foundation for further exploring whether GOLPH3 high gliomas will be more sensitive to anti-EGFR therapy in clinic and give ideas for developing new possible treatments for individual glioma patients.

Ultra-efficient spin-orbit torque induced magnetic switching in W/CoFeB/MgO structures.

Spin-orbit torque (SOT) induced magnetic switching in heavy metal/ferromagnet structures with perpendicular magnetic anisotropy (PMA) is promising for energy efficient spintronic devices. Here, we studied the SOT induced magnetic switching in perpendicular W/Co20Fe60B20/MgO structures. We demonstrated the critical current density for the SOT induced switching is as low as 1.15 × 106 A cm-2 in the presence of an in-plane magnetic field, which is very energy efficient in terms of magnetic switching. We attribute this ultra-efficient magnetic switching to the high spin Hall angle of the W layer and the ultra-low domain wall pinning field of the CoFeB. The SOT induced switching procedure was directly observed by a high-resolution Kerr microscopy. Furthermore, the weak Dzyaloshinsky-Moriya interactions are shown to be favorable for switching. Our experiments physically explained the ultra-efficient SOT induced magnetic switching in W/CoFeB/MgO structures, and direct observation of the switching procedure can improve the comprehensive understanding of this dynamic process and further promote the study of SOT based memory devices.

ß-catenin-mediated YAP signaling promotes human glioma growth.

BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma progression is largely unknown. METHODS: The expression of YAP in glioma tissues was detected by quantitative polymerase chain reaction (qPCR) and immunoblotting. The effect of YAP on glioma progression was examined using cell growth assays and intracranial glioma model. The effect of YAP on ß-catenin protein level, subcellular location and transcription activity was examined by immunoblotting, immunofluorescence and RT-PCR. RESULTS: Firstly, knockdown of YAP inhibited glioma cell proliferation in vitro and tumor growth in vivo. In addition, YAP modulated the protein level, subcellular location and transcription activity of ß-catenin via regulating the activity of GSK3ß. Lastly, ß-catenin partially mediated the effect of YAP on glioma cell proliferation. CONCLUSION: Our findings identify that YAP promotes human glioma growth through enhancing Wnt/ß-catenin signaling. In addition, this study provides a new crosstalk mechanism between Hippo/YAP and Wnt/ß-catenin pathways, which suggests a new strategy for human glioma treatment.

Golgi phosphoprotein 3 promotes glioma progression via inhibiting Rab5-mediated endocytosis and degradation of epidermal growth factor receptor.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) is associated with worse prognosis of gliomas, but its role and mechanism in glioma progression remain largely unknown. This study aimed to explore the role and mechanism of GOLPH3 in glioma progression. METHODS: The expression of GOLPH3 in glioma tissues was detected by quantitative PCR, immunoblotting, and immunohistochemistry. GOLPH3's effect on glioma progression was examined using cell growth assays and an intracranial glioma model. The effect of GOLPH3 on epidermal growth factor receptor (EGFR) stability, endocytosis, and degradation was examined by immunoblotting and immunofluorescence. The activity of Rab5 was checked by glutathione S-transferase pulldown assay. RESULTS: GOLPH3 was upregulated in gliomas, and its downregulation inhibited glioma cell proliferation both in vitro and in vivo. Furthermore, GOLPH3 depletion dampened EGFR signaling by enhancing EGFR endocytosis, driving EGFR into late endosome and promoting lysosome-mediated degradation. Interestingly, GOLPH3 bound to Rab5 and GOLPH3 downregulation promoted the activation of Rab5. In addition, Rab5 depletion abolished the effect of GOLPH3 on EGFR endocytosis and degradation. CONCLUSION: Our results imply that GOLPH3 promotes glioma cell proliferation via inhibiting Rab5-mediated endocytosis and degradation of EGFR, thereby activating the phosphatidylinositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway. We find a new mechanism by which GOLPH3 promotes tumor progression through regulating cell surface receptor trafficking. Extensive and intensive understanding of the role of GOLPH3 in glioma progression may provide an opportunity to develop a novel molecular therapeutic target for gliomas.

Protein kinase D2 promotes the proliferation of glioma cells by regulating Golgi phosphoprotein 3.

Protein kinase D2 (PKD2) has been demonstrated to promote tumorigenesis in many types of cancers. However, how PKD2 regulates cancer cell growth is largely unknown. In this study, we found that over-expression of PKD2 promoted glioma cell growth but down-regulation of PKD2 inhibited it. Further investigation indicated that PKD2 down-regulation decreased the protein level of Golgi phosphoprotein 3(GOLPH3) as well as p-AKT level. On the contrary, over-expression of PKD2 increased the protein level of GOLPH3 and p-AKT. In addition, GOLPH3 exhibited similar effect on glioma cell growth to that of PKD2. Importantly, GOLPH3 down-regulation partially abolished glioma cell proliferation induced by PKD2 over-expression, while over-expression of GOLPH3 also partially rescued the inhibition effect of PKD2 down-regulation on glioma cell growth. Interestingly, the level of PKD2 and GOLPH3 significantly increased and was positively correlated in a cohort of glioma patients, as well as in patients from TCGA database. Taken together, these results reveal that PKD2 promotes glioma cell proliferation by regulating GOLPH3 and then AKT activation. Our findings indicate that both PKD2 and GOLPH3 play important roles in the progression of human gliomas and PKD2-GOLPH3-AKT signaling pathway might be a potential glioma therapeutic target.

Versatile matrix for constructing enzyme-based biosensors.

A versatile matrix was fabricated and utilized as a universal interface for the construction of enzyme-based biosensors. This matrix was formed on the gold electrode via combining self-assembled monolayer of 2,3-dimercaptosuccinic acid with gold nanoparticles. Gold nanoparticles were electrochemically deposited. Electrochemistry of three redox enzymes (catalase, glucose oxidase, and horseradish peroxidase) was investigated on such a matrix. The electrocatalytic monitoring of hydrogen peroxide and glucose was conducted on this matrix after being coated with those enzymes. On them the monitoring of hydrogen peroxide and glucose shows rapid response times, wide linear working ranges, low detection limits, and high enzymatic affinities. This matrix is thus a versatile and suitable platform to develop highly sensitive enzyme-based biosensors.

In situ synthesized gold nanoparticles for direct electrochemistry of horseradish peroxidase.

In order to construct a three-dimensional electrode, in situ electrochemical deposition of gold nanoparticles onto a gold electrode coated with a self-assembled monolayer of 3-mercaptopropionic acid (Au NP/MPA/Au) was conducted. Horseradish peroxidase (HRP) was then immobilized into this three-dimensional electrode, leading to the realization of direct electron transfer of HRP. Scanning electron microscopy and electrochemical impedance spectroscopy were applied to characterize the electrode before and after HRP immobilization. The apparent Michaelis-Menten constant for immobilized HRP on a Au NP/MPA/Au electrode is 0.78 mM, indicating high enzymatic activity of HRP. The HRP modified electrode was further utilized as a sensing platform for the electrocatalytic reduction and detection of hydrogen peroxide. For the detection of hydrogen peroxide on this electrode, the sensitivity is 311.72 µA mM(-1) cm(-2), the detection limit is 0.16 µM, and the dynamic range is from 0.48 µM to 1.2 mM. Therefore this electrode is a promising device for sensitive and reproducible detection of H(2)O(2).

[Debating some issues on the application of auricular point].

Some issues on the auricular acupuncture including its effectiveness and side effects, the relationship of positive reaction and diseases, the key point of auricular point selection and standard auricular point popularization and application, are debated in this paper according to the authors' comprehension based on their many years clinical and teaching practice. In the paper, the authors point out that the auricular acupuncture has the characteristics of the high effective rate, low cured rate and some recurrence rate. The relationship of positive reacted point in the auricular acupuncture and disease include two kinds of reaction as "one point for multiple diseases" and "one disease for multiple points". Correct locating and reasonable selection of auricular points are the key point for using auricular point. Finally, the authors propose that standard auricular point still has not been popularized, and also, it should be paid attention to the problem of side effect induced by the auricular acupuncture.