Nano-petri-dish Array Assisted Glancing Angle Sputtering for Ag-NP Assembled Bi-nanoring Arrays as Effective SERS Substrates

Nano-petri-dish array assisted glancing angle Ag-sputtering was reported to synthesize Ag-nanoparticle (Ag-NP) assembled bi-nanoring arrays as surface-enhanced Raman scattering (SERS) substrates. By manipulating the sputtering-Ag duration, the gaps between the Ag-NPs in the bi-nanorings are tunable to acquire optimal electromagnetic field enhancement, and the ordered bi-nanoring arrays ensure excellent reproducibility for Raman measurement. Such as-fabricated Ag-NPs assembled nanoring arrays exhibit excellent SERS performance, not only 1 × 10^–12 M rhodamine 6G has been identified, but also polychlorinated biphenyls with a low concentration down to 1 × 10^–9 M has been recognized, showing great potential in the detection of trace organic pollutants in the environment

Additional file 1: of Nuclear accumulation of UBC9 contributes to SUMOylation of lamin A/C and nucleophagy in response to DNA damage

Figure S1. Nuclear DNA leakage activates nucleophagy. Figure S2. Nuclear autophagy exists in other cancer cell lines. Figure S3. LC3-lamin A/C interaction is required for nucleophagy. Figure S4. Inhibiting autophagy impairs degradation of lamin A/C. Figure S5. Lamin A/C is SUMOylated in response to DNA damage. Figure S6. UBC9 accumulates in nucleus in response to DNA damage. Figure S7. Knockdown of UBC9 attenuates SUMOylation of lamin A/C and nucleophagy mediated by DNA damage. (DOCX 6283 kb

Flexible 3D Substrate of Ag Nanoparticle-Loaded Carbon Aerogels with Outstanding Surface-Enhanced Raman Scattering Performance

Surface-enhanced Raman scattering (SERS), an ultra-sensitive and non-destructive analytic technique, has attracted wide attention from the scientific community. Despite its rapid development, limited hotspots on the SERS substrates have restricted their potential in practical applications. Herein, we developed a facile method to fabricate a flexible three-dimensional (3D) SERS substrate composed of silver nanoparticles (Ag NPs)-loaded carbon aerogels (CAs). Such a flexible Ag NPs/CAs substrate exhibited numerous hotspots, which can facilely be adjusted not only by tuning the density of Ag NPs but also by controlling the bending degree of the flexible substrate. In addition, the influence of hotspots on the local electric field enhancement was investigated by theoretical calculations. Moreover, the 3D network structure of the CAs with a large specific surface area and strong adsorption ability can improve the capture of target molecules. Consequently, the optimal Ag NPs/CAs substrate has a low detection limit of 10–12 M for rhodamine 6G molecules as well as good repeatability. Furthermore, based on the good performance of SERS detection of the Ag NPs/CAs substrate, it can also be practically used for the detection of thiram molecules on the surface of cherry tomatoes. Such a flexible 3D Ag NPs/CAs substrate has great potential for practical environmental monitoring applications

Ultrafine ZrB₂ Ceramic Powders Prepared by a Sol–Gel Method Synergized with a Carbothermic Reaction and Their Improved Sintering Performance

The sol–gel method synergized with a carbothermic reaction has been known to be one of the most promising strategies for preparing a high-quality boride and carbon-based ultrahigh-temperature ceramic, yet their growth mechanism remains underexplored. Herein, high-purity ZrB2 ceramic powders are prepared by a sol–gel method synergized with a subsequent carbothermic reaction. Specifically, sorbitol (C6H14O6) is adopted to build molecularly disperse networks of Zr–O–C–B. Structural characterizations reveal that the calcination temperature and duration have a great influence on the phase and morphological transformation of the precursor. The ZrB2 seeds start to be generated near ZrO2 particles around 1100 °C and grow from the surface to the core of ZrO2 particles with heat and mass transportation around ZrO2 driven by B2O3 at high temperature. Additionally, the ZrB2 powders could research a hardness of 22.5 GPa and a bending strength of 540 MPa after sintering, showing improved mechanical properties. This work reveals the growth mechanism of ultrafine and high-purity ZrB2 powders by a sol–gel method and a carbothermic reaction, which can be used as raw materials to obtain ZrB2 ultrahigh-temperature ceramics with improved mechanical properties

T2A inhibited the transcriptional activity of HIF-1α, but had no significant effects on the HIF-1α mRNA level.

<p>(A) The MDA-MB-231 cells were treated without or with various concentrations of T2A for 24 hour under normoxic or hypoxic conditions. VEGF in the supernatant was evaluated using ELISA. Error bars represent means ± S.D. (n = 3). (B) The MDA-MB-231 cells were transfected with pBI-GL V6L plasmid, pRL-SV-40 plasmid and HIF-1α plasmid (HIF-1α overexpression group) or an empty vector plasmid (control). Cells were treated with T2A or DMSO. The promoter activity of HIF-1α was analyzed as described in the Methods section. **<i>P</i>< 0.01 compared with the control. (C and D) Total cellular RNA was extracted and the HIF-1α, VEGF, Glut1, and EPO mRNA levels were evaluated using real-time PCR. The relative mRNA levels of HIF-1α, VEGF, Glut1, and EPO were normalized according to the β-actin abundance and expressed as percentages of the control. Error bars represent means ± SD (n = 3).</p

A novel autophagy/mitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission

<p>Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that liensinine, a major isoquinoline alkaloid, inhibits late-stage autophagy/mitophagy through blocking autophagosome-lysosome fusion. This effect is likely achieved via inhibiting the recruitment of RAB7A to lysosomes but not to autophagosomes. We further investigated the effects of autophagy inhibition by liensinine on the therapeutic efficacy of chemotherapeutic drugs and found that cotreatment of liensinine markedly decreased the viability and increased apoptosis in breast cancer cells treated with various chemotherapeutic agents. Mechanistically, we found that inhibition of autophagy/mitophagy by liensinine enhanced doxorubicin-mediated apoptosis by triggering mitochondrial fission, which resulted from dephosphorylation and mitochondrial translocation of DNM1L. However, blocking autophagosome/mitophagosome formation by pharmacological or genetic approaches markedly attenuated mitochondrial fission and apoptosis in cells with combinatatorial treatment. Moreover, liensinine was synergized with doxorubicin to inhibit tumor growth in MDA-MB-231 xenograft in vivo. Our findings suggest that liensinine could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of liensinine with classical chemotherapeutic drugs could represent a novel therapeutic strategy for treatment of breast cancer.</p

T2A inhibited HIF-1α expression in MDA-MB-231 and MCF-7 cells.

<p>(A and B) The MDA-MB-231 and MCF-7 cells were treated without or with various concentrations of T2A for 16 hours and then subjected to hypoxia, or remained in normoxia for an additional 8 hours. Whole cell extracts (WCE) and nuclear extracts (NE) were prepared from cells and subjected to Western blot assay using antibodies against HIF-1α, HIF-2α, HIF-1β, and β-actin. (C) Cells were fixed, permeabilized, and processed for immunofluorescence labeling with anti-Tubulin (Red) and anti-HIF-1α (green) antibodies. Nuclei were counterstained with 0.1 μg/ml DAPI (blue). Scale bar represents 10 μm.</p

T2A inhibited HIF-1α expression through the inhibition of protein synthesis rather than the promotion of HIF-1α degradation.

<p>(A) The MDA-MB-231 cells were cultured under normoxic or hypoxic conditions for 8 hours, then pretreated without or with 20 μM T2A for 30 minutes, followed by treatment without or with 20 μM cycloheximide (CHX) for various intervals as indicated. Upper panel: after treatment, whole cell extracts were analyzed by Western blot using antibodies against HIF-1α and β-actin. Lower panel: quantification of the HIF-1α by densitometry following normalization to the β-actin level. The HIF-1α protein levels in untreated or T2A-treated cells were arbitrarily given the value of 100%. (B) Cells were labeled with [³⁵S]methionine as described in the Methods section and chased for the indicated periods (h) in the presence or absence of T2A under normoxic or hypoxic conditions. Upper panel: equal amounts of proteins from each cell lysate were subjected to immunoprecipitation and then separated in SDS-PAGE and examined by autoradiography following normalization to the control. Lower panel: quantification of the autoradiographic HIF-1α signal by densitometry. (C) Cells were pretreated with either vehicle or 20 μM T2A for 16 hours and then subjected to hypoxia, or remained in normoxia for an additional 8 hours. Subsequently, cells were labeled with [³⁵S]methionine in the presence or absence of 20 μM T2A for the indicated time. Upper panel: Equal amounts of proteins were subjected to immunoprecipitation and then separated in SDS-PAGE and examined by autoradiography. Lower panel: quantification of the autoradiographic HIF-1α signal by densitometry. (D) Cells were pretreated with the proteasome inhibitor MG132 (10 μM) for 2 hours, followed by T2A treatment (20 μM) under normoxic or hypoxic conditions as described above. Whole cell extracts were analyzed by Western blot using antibodies against HIF-1α and β-actin.</p

A 2.6 V Flexible Supercapacitor Based on Al-MnO₂‑Na₂SO₄//AC-KOH with High Specific Energy

In this work, we have synthesized Al-doped MnO2 nanoparticles (Al-MnO2) by rapid coprecipitation followed by hydrothermal and heat treatment. Al-MnO2 shows a specific capacitance of 301.8 F g–1 at 1 A g–1 in a sample of 14% Al-MnO2-260 °C. The specific capacitance still remains at 206 F g–1 at 20 A g–1. It also shows a good cycling stability with no capacitance degradation after 5000 cycles. More importantly, a new type of supercapacitor, Al-MnO2|PVA-Na2SO4//PVA-KOH|AC, has been designed using a Na2SO4-poly(vinyl alcohol)//cation exchange membrane//KOH-poly(vinyl alcohol)-based decoupled electrolyte. This device exhibits a specific capacitance of 68.9 F g–1 at 1 A g–1, corresponding to 64.7 Wh kg–1 at 1300 W kg–1. It also delivers a good capacitance retention of ∼84% after 5000 cycles. The cell voltage is up to 2.6 V, which could light up a green light-emitting diode. The PVA-based decoupled gel electrolyte offers good processability to assemble flexible and foldable devices, which is important for mass production in manufacturing. These results clearly indicate that such high-voltage flexible supercapacitors with high specific energy are very promising in future wearable electronics

T2A inhibited angiogenesis and tumor growth <i>in vivo</i>.

<p>Xenograft mouse models on the back of nude mice were established using human MDA-MB-231 cells (2 × 10⁶). Tumor mice were treated with T2A or vehicle as described in the Methods section. Tumor growth and body weight of mice were measured once a week. (A) Average tumor volume of vehicle control mice and mice treated with T2A. Values of tumor volume from the T2A-treated group were significantly reducted compared with those from mice of the control group based on Student’s t test; *<i>P</i> < 0.05 or **<i>P</i> < 0.01. (B) Body weight of mice during the eight weeks of T2A treatment. (C) Representative tumors from the control and T2A-treated groups. (D) Average hemoglobin levels in tumor tissues from 4 vehicle control and 4 T2A-treated mice. **<i>P</i> < 0.01 compared with vehicle control. (E) Representative tumor sections were immunostaining by using CD31 antibody. Scale bar represents 20 μm. (F) Microvessel density (MVD) was counted the CD31-positive blood vessels per field (400 × magnification) from four replicate tumor sections. **<i>P</i> < 0.01 compared with vehicle control. (G) Total cellular RNA were extracted from tumors in 4 vehicle control and 4 T2A-treated mice and the VEGF mRNA level was evaluated using real-time PCR. **<i>P</i> < 0.01 compared with vehicle control. (H) Tumors from 1 vehicle control mouse and 1 T2A-treated mice were surgically removed and homogenized. Whole tumor lysates were prepared and subjected to Western blot assay using antibodies as indicated.</p