Fixed-Point Atomic Regulation Engineered Low-Thickness Wideband Microwave Absorption.

Atomic doping is widely employed to fine-tune crystal structures, energy band structures, and the corresponding electrical properties. However, due to the difficulty in precisely regulating doping sites and concentrations, establishing a relationship between electricity properties and doping becomes a huge challenge. In this work, a modulation strategy on A-site cation dopant into spinel-phase metal sulfide Co9S8 lattice via Fe and Ni elements is developed to improve the microwave absorption (MA) properties. At the atomic scale, accurately controlling doped sites can introduce local lattice distortions and strain concentration. Tunned electron energy redistribution of the doped Co9S8 strengthens electron interactions, ultimately enhancing the high-frequency dielectric polarization (ɛ' from 10.5 to 12.5 at 12 GHz). For the Fe-doped Co9S8, the effective absorption bandwidth (EAB) at 1.7 mm increases by 5%, and the minimum reflection loss (RLmin) improves by 26% (EAB = 5.8 GHz, RLmin = -46 dB). The methodology of atomic-scale fixed-point doping presents a promising avenue for customizing the dielectric properties of nanomaterials, imparting invaluable insights for the design of cutting-edge high-performance microwave absorption materials.

Wrinkle Structure Regulating Electromagnetic Parameters in Constructed Core-shell ZnFe2O4@PPy Microspheres as Absorption Materials.

Structure engineering of magnetic-dielectric multi-components is emerging as an effective approach for presuming high-performance electromagnetic (EM) absorption, but still faces bottlenecks due to the ambiguous regulation mechanism of surface morphology. Here, a novel wrinkled surface structure is tailored on the ZnFe2O4 microsphere via a spray-pyrolysis induced Kirkendall diffusion effect, the conductivity of the sample is affected, and a better impedance matching is adjusted by modulating the concentration of metal nitrate precursors. Driven by a vapor phase polymerization, conductive polypyrrole (PPy) shell are in situ decorated on the ZnFe2O4 microsphere surfaces, ingeniously constructing a core-shell ZnFe2O4@PPy composites. Moreover, a systematic investigation reveals that this unique wrinkled surface structure is highly dependent on the metal salt concentration. Optimized wrinkle ZnFe2O4@PPy composite exhibits a minimum reflection loss (RLmin) reached -41.0 dB and the effective absorption bandwidth (EAB) can cover as wide as 4.1 GHz. The enhanced interfacial polarization originated from high-density ZnFe2O4-PPy heterostructure, and the conduction loss of PPy contributes to the boosted dielectric loss capability. This study gives a significant guidance for preparing high-performance EM composites by tailoring the surface wrinkle structure.

PARP1 negatively regulates transcription of BLM through its interaction with HSP90AB1 in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a prevalent malignant disease affecting a significant number of males globally. Elevated expression of the Bloom's syndrome protein (BLM) helicase has emerged as a promising cancer biomarker, being associated with the onset and progression of PCa. Nevertheless, the precise molecular mechanisms governing BLM regulation in PCa remain elusive. METHODS: The expression of BLM in human specimens was analyzed using immnohistochemistry (IHC). A 5'-biotin-labeled DNA probe containing the promoter region of BLM was synthesized to pull down BLM promoter-binding proteins. Functional studies were conducted using a range of assays, including CCK-8, EdU incorporation, clone formation, wound scratch, transwell migration, alkaline comet assay, xenograft mouse model, and H&E staining. Mechanistic studies were carried out using various techniques, including streptavidin-agarose-mediated DNA pull-down, mass spectrometry (MS), immunofluorescence (IF), dual luciferase reporter assay system, RT-qPCR, ChIP-qPCR, co-immunoprecipitation (co-IP), and western blot. RESULTS: The results revealed significant upregulation of BLM in human PCa tissues, and its overexpression was associated with an unfavorable prognosis in PCa patients. Increased BLM expression showed significant correlations with advanced clinical stage (P = 0.022) and Gleason grade (P = 0.006). In vitro experiments demonstrated that BLM knockdown exerted inhibitory effects on cell proliferation, clone formation, invasion, and migration. Furthermore, PARP1 (poly (ADP-ribose) polymerase 1) was identified as a BLM promoter-binding protein. Further investigations revealed that the downregulation of PARP1 led to increased BLM promoter activity and expression, while the overexpression of PARP1 exerted opposite effects. Through mechanistic studies, we elucidated that the interaction between PARP1 and HSP90AB1 (heat shock protein alpha family class B) enhanced the transcriptional regulation of BLM by counteracting the inhibitory influence of PARP1 on BLM. Furthermore, the combination treatment of olaparib with ML216 demonstrated enhanced inhibitory effects on cell proliferation, clone formation, invasion, and migration. It also induced more severe DNA damage in vitro and exhibited superior inhibitory effects on the proliferation of PC3 xenograft tumors in vivo. CONCLUSIONS: The results of this study underscore the significance of BLM overexpression as a prognostic biomarker for PCa, while also demonstrating the negative regulatory impact of PARP1 on BLM transcription. The concurrent targeting of BLM and PARP1 emerges as a promising therapeutic approach for PCa treatment, holding potential clinical significance.

BLM promotes malignancy in PCa by inducing KRAS expression and RhoA suppression via its interaction with HDGF and activation of MAPK/ERK pathway.

Prostate cancer (PCa) has long been the leading cause of cancer-associated deaths among male worldwide. Our previous studies have shown that Bloom syndrome protein (BLM) plays a vital role in PCa proliferation, yet the underlying molecular mechanism remains largely obscure. Mechanistically, BLM directly interacted with hepatoma-derived growth factor (HDGF). Functionally, BLM and HDGF knockdown resulted in the higher impairment of PC3 proliferation, clonogenicity, migration and invasion than that their counterpart with either BLM or HDGF knockdown exclusively. Of note, HDGF overexpression expedited, whereas its knockdown suppressed, PC3 proliferation, clonogenicity, migration and invasion. Additionally, the potentiation or attenuation was partially antagonized upon BLM depletion or overexpression. In line with the vitro data, the impact of BLM and HDGF on tumor growth was investigated in mouse xenograft models. ChIP-seq, dual-luciferase reporter and western blotting assays were employed to expound the regulatory network in PC3 cells. The results unveiled that HDGF activated KRAS and suppressed RhoA transcription, and that the function of HDGF was mediated, in part, by interaction with BLM. Accordingly, the MAPK/ERK pathway was activated. Moreover, the regulation of HDGF on KRAS and RhoA had a signal crosstalk. To recapitulate, BLM and HDGF may serve as novel prognostic markers and potential therapeutic targets in PCa.

One-Dimensional Magnetic FeCoNi Alloy Toward Low-Frequency Electromagnetic Wave Absorption.

Rational designing of one-dimensional (1D) magnetic alloy to facilitate electromagnetic (EM) wave attenuation capability in low-frequency (2-6 GHz) microwave absorption field is highly desired but remains a significant challenge. In this study, a composite EM wave absorber made of a FeCoNi medium-entropy alloy embedded in a 1D carbon matrix framework is rationally designed through an improved electrospinning method. The 1D-shaped FeCoNi alloy embedded composite demonstrates the high-density and continuous magnetic network using off-axis electronic holography technique, indicating the excellent magnetic loss ability under an external EM field. Then, the in-depth analysis shows that many factors, including 1D anisotropy and intrinsic physical features of the magnetic medium-entropy alloy, primarily contribute to the enhanced EM wave absorption performance. Therefore, the fabricated EM wave absorber shows an increasing effective absorption band of 1.3 GHz in the low-frequency electromagnetic field at an ultrathin thickness of 2 mm. Thus, this study opens up a new method for the design and preparation of high-performance 1D magnetic EM absorbers.

Preferential Co substitution on Ni sites in Ni-Fe oxide arrays enabling large-current-density alkaline oxygen evolution.

Developing low-cost and high-activity transition metal oxide electrocatalysts for an efficient oxygen evolution reaction (OER) at a large current density is highly demanded for industrial application and remains a big challenge. Herein, we report vertically aligned cobalt doped Ni-Fe based oxide (Co-NiO/Fe2O3) arrays as a robust OER electrocatalyst via a simple method combining hydrothermal reaction with heat treatment. Density functional theory calculation and XRD Rietveld refinement reveal that Co preferentially occupies the Ni sites compared to Fe in the Ni-Fe based oxides. The electronic structures of the Co-NiO/Fe2O3 could be further optimized, leading to the improvement of the intrinsic electronic conductivity and d-band center energy level and the decrease in the reaction energy barrier of the rate-determining step for the OER, thus accelerating its OER electrocatalytic activity. The Co-NiO/Fe2O3 nanosheet arrays display state-of-the-art OER activities at a large current density for industrial demands among Fe-Co-Ni based oxide electrocatalysts, which only require an ultra-low overpotential of 230 mV at a high current density of 500 mA cm-2, and exhibit superb durability at 500 mA cm-2 for at least 300 h without obvious degradation. The Co-NiO/Fe2O3 nanosheet arrays also have a small Tafel slope of 33.9 mV dec-1, demonstrating fast reaction kinetics. This work affords a simple and effective method to design and construct transition metal oxide based electrocatalysts for efficient water oxidation.

Magnetic Interacted Interaction Effect in MXene Skeleton: Enhanced Thermal-Generation for Electromagnetic Interference Shielding.

With the rapid advancements of portable and wearable equipment, high-efficiency electromagnetic interference (EMI) shielding materials are highly entailed to eliminate radiated electromagnetic pollution. Herein, by assembling hexagonal SrFe12 O19 flakes into a Ti3 C2 Tx MXene/MWCNT substrate, a magnetized Ti3 C2 Tx -based film is successfully fabricated by a facile filtration approach. Carbon nanotubes are used as isolation agents to realize the submicroscopic dispersion of MXene and SrFe12 O19 . The obtained MXene/MWCNTs/SrFe12 O19 film shows a high electrical conductivity of 438 S cm-1 and an excellent EMI shielding effectiveness of 62.9 dB in X-band at a thickness of only 40 µm. Benefiting from a strong magnetic response ability and an expanded magnetic coupling space, hexagonal SrFe12 O19 sheets can efficiently consume incident magnetic field energy by domain wall migration and the ferromagnetic resonance effect. Boosted EMI shielding performance can be achieved by improving the magnetic loss in the Ti3 C2 Tx MXene/MWCNTs/SrFe12 O19 film, preventing the secondary reflection of electromagnetic waves. Meanwhile, magnetized MXene-based films display the freestanding and flexible features and are suitable for installation in electric devices. It is anticipated that this strategy offers new ideas for designing EMI shielding films and in broadening potential utility of MXene-based materials.

Inhibition of NOS1 promotes the interferon response of melanoma cells.

BACKGROUND: NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown. METHODS: The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer. RESULTS: NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN[Formula: see text] by upregulation expression of IFN[Formula: see text] simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients. CONCLUSION: These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.

[Historical evolution of Salviae Miltiorrhizae Radix et Rhizoma processing methods].

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.

Single Zinc Atoms Anchored on MOF-Derived N-Doped Carbon Shell Cooperated with Magnetic Core as an Ultrawideband Microwave Absorber.

Polarization behaviors of no-magnetic shell dominate the dielectric properties for core-shell magnetic-carbon composites, which faces a huge challenge. Herein, a single atom-doping strategy is established to adjust local electric potential in the metal-organic framework (MOF)-derived carbon shell. Benefiting from the confined transformation, single Zn atoms and N atoms are evenly distributed in the porous carbon shell using ZIF-8 as a template. Dielectric assembled carbon layers with functionalized Fe3 O4 core construct unique magnetic-dielectric synergy system. The electromagnetic parameters of Fe3 O4 @Zn-N-Carbon composites can be modified by tuning the pod-like Zn-N-doping carbon shell via repeating ZIF-8 growth cycles. Surprisingly, the core-shell Fe3 O4 @Zn-N-Carbon exhibits superior microwave absorption (MA) performance both in the reflection loss ability and wide-frequency responding feature. The reflection loss value of Fe3 O4 @Zn-N-Carbon microspheres reach -61.9 dB and the effective absorption bandwidth up to 11.5 GHz at only 2.5 mm thickness. The excellent MA mechanism is ascribed to following reasons. High-density stacking Zn-N doping carbon layers boost the interfacial polarization and plentiful Zn single atoms maximize the dipole polarization because of maximum atom utilization efficiency. Enhanced magnetic loss ability results from the compulsory magnetic coupling responding among Fe3 O4 cores. Magnetic-dielectric synergy of core-shell Fe3 O4 @Zn-N-Carbon microspheres can build ultrawide MA frequency.

Confined Magnetic-Dielectric Balance Boosted Electromagnetic Wave Absorption.

Magnetic-dielectric property plays a critical significance for the functional expression toward advanced materials. Within nanoscale, the simultaneous regulation of the electrical and magnetic properties of electromagnetic (EM) wave absorption materials faces huge challenges. Herein, using the metal-organic frameworks (MOF) as templates, highly-dispersed ZnO and Co nanoparticles are uniformly confined inside graphited N-doped carbon skeleton, constructing the balanced EM property in the Co@NC-ZnO absorbers. Meanwhile, a dynamics and symmetrical morphology optimization of MOF-derived Co@NC-ZnO are dependent on the Co/Zn mass ratio and adjusting MOF frameworks, which evolves from the cube, truncated cube, dodecahedron, and to the final microsphere. Simultaneously, both the electronic conduction network and magnetic coupling network are compatible together in the in situ transformed Co@NC-ZnO system. Boosted magnetic responding ability and unique magnetic coupling are verified by the off-axis electronic holography. Plentiful heterojunction interfaces and special electronic conduction paths can be built in this Co-Zn-MOF derivatives, facilitating the dielectric loss behaviors. As expected, MOF-derived Co@NC-ZnO absorber displays outstanding EM wave absorption ability with strongest reflection loss value of -69.6 dB at only 1.9 mm thickness and wideband absorption covering 6.8 GHz at 2.4 mm. Confined EM balance provides new design strategy toward MOF-derived excellent MA materials and functional devices.

Selection of appropriate post-harvest processing methods based on the metabolomics analysis of Salvia miltiorrhiza Bunge.

Post-harvest processing is a leading cause of metabolic changes and quality loss in food products. An untargeted metabolomics approach based on UHPLC-QTOF-MS was conducted to explain metabolic changes during post-harvest processing of Salvia miltiorrhiza. A rapid identification method was established for comprehensive characterization of 56 phenolic acids and 45 tanshinones. Enzymatic browning was found to be the primary factor impacting the metabolic profile. A decreasing in free phenolic acids along with increasing in bound polyphenols was observed correlated with the deepening of browning degree. The various substructures of bound polyphenols were explored to interpret the composition of browning-associated products. It has also been found that the steaming process and control of the moisture content during slicing can effectively reduce the influence of enzymatic browning. This metabolomics study will contribute to select the optimal post-harvest processing methods for S. miltiorrhiza and provide information for post-harvest processing of similar products.

The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells.

One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.

Recent progress of microwave absorption microspheres by magnetic-dielectric synergy.

Designing and developing high-performance microwave absorption (MA) materials for electromagnetic protection and radar detection have received widespread attention. Recently, magnetic-dielectric MA materials have become a research hotspot due to their unique complementary functions and synergy loss mechanism. Herein, we review important research progress of excellent MA systems combining strong magnetic components and dielectric substrates. The functional materials involve magnetic materials, carbon components, semiconductors, polymer and so on. For a comprehensive analysis, current development and challenges are firstly introduced in the background. Modern requirements for microwave energy conversion are elaborated in the following part. To highlight the key points, more attention has been paid to the magnetic-dielectric synergy microsphere: (i) core/yolk-shell structure, (ii) multi-component assembly and (iii) MOF-derived synergy composites. Meanwhile, classical and typical high-performance MA composites with a multi-loss mechanism are also mentioned in this review paper. Finally, the design principles, electromagnetic synergy, future mechanism exploration and device application are presented, which provides guidance for understanding MA materials.

The heterocyclic compound Tempol inhibits the growth of cancer cells by interfering with glutamine metabolism.

Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.

Multidimension-Controllable Synthesis of MOF-Derived Co@N-Doped Carbon Composite with Magnetic-Dielectric Synergy toward Strong Microwave Absorption.

Metal-organic framework (MOF) is highly desirable as a functional material owing to its low density, tunable pore size, and diversity of coordination formation, but limited by the poor dielectric properties. Herein, by controlling the solvent and mole ratio of cobalt/linker, multidimension-controllable MOF-derived nitrogen-doped carbon materials exhibit tunable morphology from sheet-, flower-, cube-, dodecahedron- to octahedron-like. Tunable electromagnetic parameters of Co@N-doped carbon composites (Co@NC) can be obtained and the initial MOF precursor determines the distribution of carbon framework and magnetic cobalt nanoparticles. Carbonized Co@NC composites possess the following advantages: i) controllable dimension and morphology to balance the electromagnetic properties with evenly charged density distribution; ii) magnetic-carbon composites offer plenty of interfacial polarization and strong magnetic coupling network; iii) a MOF-derived dielectric carbon skeleton provides electronic transportation paths and enhances conductive dissipation. Surface-mediated magnetic coupling reflects the stray magnetic flux field, which is corroborated by the off-axis electron holography and micro-magnetic simulation. Optimized octadecahedral Co@NC sample exhibits the best microwave absorption (MA) of -53.0 dB at the thickness of 1.8 mm and broad effective frequency from 11.4 to 17.6 GHz (Ku-band). These results pave the way to fabricate high-performance MA materials with balanced electromagnetic distribution and controlled morphology.

Microcystins-LR induced apoptosis via S-nitrosylation of GAPDH in colorectal cancer cells.

Microcystins-LR (MC-LR), a cyanobacterial toxins, initiate apoptosis in normal and tumor cells. Nitric oxide produced by iNOS is necessary for MC-LR-induced apoptosis. However, the underlying mechanism of NO mediated MC-LR cytotoxicity remains unclear. Here, we performed in vitro experiments on MC-LR cytotoxicity associated with NO induced S-nitrosyation of GAPDH in human colon cancer cells SW480. MTT assay indicated that MC-LR decreased the cellular viability by high concentration (>1 µM). Flow cytometer assay revealed that apoptosis was core mode for MC-LR cytotoxicity. Griess assay showed that MC-LR exposure increased the release of NO through the function of NOS1 and NOS2 in SW480 cells. In turn, NO stress induced the S-nitrosylated modification of GAPDH leading to its nuclear translocation following Siah1 binding. CHIP assay showed that the nuclear GADPH increased P53 transcript of a panner of apoptosis related genes. Moreover, apoptosis induced by MC-LR could be reduced by GAPDH or si-Siah1 or NOSs inhibitor, L-NAME. Thus, our study verified a molecular mechanism of NO/GAPDH/Siah1 cascade in MC-LR mediated apoptosis in colorectal cancer cells, providing a further understanding the in vitro molecular mechanism of MC-LR colorectal toxicity.

MOF-Derived Ni1-xCox@Carbon with Tunable Nano-Microstructure as Lightweight and Highly Efficient Electromagnetic Wave Absorber.

Intrinsic electric-magnetic property and special nano-micro architecture of functional materials have a significant effect on its electromagnetic wave energy conversion, especially in the microwave absorption (MA) field. Herein, porous Ni1-xCox@Carbon composites derived from metal-organic framework (MOF) were successfully synthesized via solvothermal reaction and subsequent annealing treatments. Benefiting from the coordination, carbonized bimetallic Ni-Co-MOF maintained its initial skeleton and transformed into magnetic-carbon composites with tunable nano-micro structure. During the thermal decomposition, generated magnetic particles/clusters acted as a catalyst to promote the carbon sp2 arrangement, forming special core-shell architecture. Therefore, pure Ni@C microspheres displayed strong MA behaviors than other Ni1-xCox@Carbon composites. Surprisingly, magnetic-dielectric Ni@C composites possessed the strongest reflection loss value - 59.5 dB and the effective absorption frequency covered as wide as 4.7 GHz. Meanwhile, the MA capacity also can be boosted by adjusting the absorber content from 25% to 40%. Magnetic-dielectric synergy effect of MOF-derived Ni1-xCox@Carbon microspheres was confirmed by the off-axis electron holography technology making a thorough inquiry in the MA mechanism.

NOS1 inhibits the interferon response of cancer cells by S-nitrosylation of HDAC2.

BACKGROUND: The dysfunction of type I interferon (IFN) signaling is an important mechanism of immune escape and metastasis in tumors. Increased NOS1 expression has been detected in melanoma, which correlated with dysfunctional IFN signaling and poor response to immunotherapy, but the specific mechanism has not been determined. In this study, we investigated the regulation of NOS1 on the interferon response and clarified the relevant molecular mechanisms. METHODS: After stable transfection of A375 cells with NOS1 expression plasmids, the transcription and expression of IFNα-stimulated genes (ISGs) were assessed using pISRE luciferase reporter gene analysis, RT-PCR, and western blotting, respectively. The effect of NOS1 on lung metastasis was assessed in melanoma mouse models. A biotin-switch assay was performed to detect the S-nitrosylation of HDAC2 by NOS1. ChIP-qPCR was conducted to measure the binding of HDAC2, H4K16ac, H4K5ac, H3ac, and RNA polymerase II in the promoters of ISGs after IFNα stimulation. This effect was further evaluated by altering the expression level of HDAC2 or by transfecting the HDAC2-C262A/C274A site mutant plasmids into cells. The coimmunoprecipitation assay was performed to detect the interaction of HDAC2 with STAT1 and STAT2. Loss-of-function and gain-of-function approaches were used to examine the effect of HDAC2-C262A/C274A on lung metastasis. Tumor infiltrating lymphocytes were analyzed by flow cytometry. RESULTS: HDAC2 is recruited to the promoter of ISGs and deacetylates H4K16 for the optimal expression of ISGs in response to IFNα treatment. Overexpression of NOS1 in melanoma cells decreases IFNα-responsiveness and induces the S-nitrosylation of HDAC2-C262/C274. This modification decreases the binding of HDAC2 with STAT1, thereby reducing the recruitment of HDAC2 to the ISG promoter and the deacetylation of H4K16. Moreover, expression of a mutant form of HDAC2, which cannot be nitrosylated, reverses the inhibition of ISG expression by NOS1 in vitro and decreases NOS1-induced lung metastasis and inhibition of tumor infiltrating lymphocytes in a melanoma mouse model. CONCLUSIONS: This study provides evidence that NOS1 induces dysfunctional IFN signaling to promote lung metastasis in melanoma, highlighting NOS1-induced S-nitrosylation of HDAC2 in the regulation of IFN signaling via histone modification.

Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1α/PFKFB3/PFK1 pathway.

AIMS: Enhanced aerobic glycolysis is an essential hallmark of malignant cancer. Blocking the glycolytic pathway has been suggested as a therapeutic strategy to impair the proliferation of tumor cells. Metformin, a widely used anti-diabetes drug, exhibits anti-tumor properties. However, the underlying molecular mechanism of its action linking glucose metabolism with the suppression of proliferation has not been fully clarified. MAIN METHODS: Stable isotope tracing technology and gas chromatography-mass spectrometry method were utilized to analyze the effect of metformin on glycolytic flux in HCC cells. Western blot and immunohistochemistry were utilized to analyze the expression of phosphofructokinase-1 (PFK1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in HCC cells or xenograft tumor tissues. Lactate measurement and glucose uptake assay were used to analyze the level of lactate and glucose in the presence of frucose-2,6-diphosphate (F2,6BP) in HCC cells treated with metformin. KEY FINDINGS: We found that metformin significantly impaired hepatoma cell proliferation by inhibiting the glycolytic flux via PFK1 blockade. Interestingly, activation of PFK1 by F2,6BP reverses the inhibitory effect of metformin on hepatoma cell proliferation and glycolysis. Mechanistically, PFKFB3，a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1α) accumulation mediated by metformin. SIGNIFICANCE: Taken together these data indicate that HIF-1α/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.