Exosomes are membrane-enclosed phospholipid extracellular vesicles, which can act as mediators of intercellular communication. Although the original features endow tumor-derived exosomes great potential as biomarkers, efficient isolation and detection methods remain challenging. Here, we presented a two-stage microfluidic platform (ExoPCD-chip), which integrates on-chip isolation and in situ electrochemical analysis of exosomes from serum. To promote exosomes capture efficiency, an improved staggered Y-shaped micropillars mixing pattern was designed to create anisotropic flow without any surface modification. By combining magnetic enrichment based on specific phosphatidylserine-Tim4 protein recognition with a new signal transduction strategy in a chip for the first time, the proposed platform enables highly sensitive detection for CD63 positive exosomes as low as 4.39 × 10 3 particles/mL with a linear range spanning 5 orders of magnitude, which is substantially better than the existing methods. The reduced volume of sample (30 μL) and simple affinity method also make it ideal for rapid downstream analysis of complex biofluids within 3.5 h. As a proof-of-concept, we performed exosomes analysis in human serum and liver cancer patients can be well discriminated from the healthy controls by the ExoPCD-chip. These results demonstrate that this proposed ExoPCD-chip may serve as a comprehensive exosome analysis tool and potential noninvasive diagnostic platform.

The existence of rechargeable lithium ion batteries with high operating voltage, high energy density, and excellent cycling performance are drawing increasing attention due to their viability to be used as portable power and in electrical applications. However, there is a considerable problem that the conductivity of the active material becomes poor due to the volume expansion under the condition of repeated circulation, which reduces the performance of the device, thus hindering its practical application. As an emerging 2D material, black phosphorus (BP) has drawn significant attention in the field of Li‐ion battery energy storage due to its large theoretical capacity of 2596 mA h g−1 and ability to absorb large amount of Li atoms. Here, a unique 3D conductive structure with the BP and carbon nanotubes (CNTs), displaying good stability and high conductivity for the fabrication of BP@CNTs hybrid‐based Li‐ion batteries is described. With strong trapping, good affinity, structure stable, and high adsorption for polyphosphorus, the developed BP@CNTs hybrid electrodes display high capacity, good electrical conductivity, and a stable cycle life. Additionally, the lithium ion batteries can illuminate the light emitting diode, proving that the materials have great potential for development of energy storage devices.

Edited by Tamas DalmayKeywords: MiR-199a-5p DRAM1 Beclin1 Autophagy Irradiation a b s t r a c t Autophagy is a self-degrading process that is triggered by diverse stimuli including ionizing radiation. In this study we show novel phenomena in which transfection of miR-199a-5p mimic significantly suppresses IR-induced autophagy in MCF7 cells, and up-regulates basal and IR-induced autophagy in MDA-MB-231 breast cancer cells. We also identify DRAM1 and Beclin1 as novel target genes for miR-199a-5p. Overexpression of miR-199a-5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA-MB-231 cells. Furthermore, we show that miR-199a-5p sensitizes MDA-MB-231 cells to irradiation. Therefore, our data identify miR-199a-5p as a novel and unique regulator of autophagy, which plays an important role in cancer biology and cancer therapy.

MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients’ serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = –0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.

Nitric oxide (NO) is a transcellular messenger involved in many physiological and pathological processes, but the real-time detection of NO in biological systems is still challenging due to its rapid diffusion, low concentration, and short half-life. A novel electrochemical sensing platform based on iron phthalocyanine (FePc) functionalized nitrogen-doped graphene (N-G) nanocomposites was constructed to achieve in situ monitoring of NO released from living cells on the sensing layer. By taking advantage of the synergetic effect of N-G and FePc nanocomposites, the N-G/FePc sensor displays excellent electrocatalytic activity toward NO with a high sensitivity of 0.21 μA μM cm and a low detection limit of 180 nmol L. The following layer-by-layer assembly of poly-l-lysine (PLL) and Nafion further improved the capacity of resisting disturbance as well as the biocompatibility of the sensing interface. The flexible design of the ITO substrate based electrode provides a more controlled cellular biosensing system which could capture molecular signals immediately after NO released from human umbilical vein endothelial cells (HUVECs). The exhibited additional features of high sensitivity, rapid response, and ease of operation implies that the proposed N-G/FePc/Nafion/PLL ITO biosensor is a promising powerful platform in various complex biological systems.

Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 ≈ 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.

widely used alkali metal; however, it will be likely replaced with other alkali elements in the foreseeable future due to the limited Li reserves in the Earth's crust. [2] Therefore, the development of next-generation cost-effective sustainable energy storage system represents an urgent task. Sodium and potassium metals with relatively large ionic radii and electronic structures similar to that of Li have become promising candidates as the anode materials of alkali-metal-ion batteries because of their abundant reserves, high theoretical capacities, and low redox potentials close to Li + /Li. [3,4] Unfortunately, the high repulsive forces generated during the ion insertion and extraction processes occurring in sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) significantly limit their large-scale commercial applications. Therefore, it is necessary to identify suitable host materials for the both the larger sodium ions (Na + ) and potassium ions (K + ).The convergence of biological and synthetic materials is a cutting-edge subject that offers significant potential to develop bionic hybrid materials with improved properties, especially in the context of energy storage. [5,6] With unique functions, the 1D hierarchical nanostructure is one of the most promising type of high efficiency materials. This type of Owing to their cost-effectiveness and high energy density, sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are becoming the leading candidates for the next-generation energy-storage devices replacing lithiumion batteries. In this work, a novel Fe x−1 Se x heterostructure is prepared on fungus-derived carbon matrix encapsulated by 2D Ti 3 C 2 T x MXene highly conductive layers, which exhibits high specific sodium ion (Na + ) and potassium ion (K + ) storage capacities of 610.9 and 449.3 mAh g −1 at a current density of 0.1 A g −1 , respectively, and excellent capacity retention at high chargedischarge rates. MXene acts as conductive layers to prevent the restacking and aggregation of Fe x−1 Se x sheets on fungus-derived carbonaceous nanoribbons, while the natural fungus functions as natural nitrogen/carbon source to provide bionic nanofiber network structural skeleton, providing additional accessible pathways for the high-rate ion transport and satisfying surfacedriven contribution ratios at high sweep rates for both Na/K ions storages. In addition, in situ synchrotron diffraction and ex situ X-ray photoelectron spectroscopy measurements are performed to reveal the mechanisms of storage and de-/alloying conversion process of Na + in the Fe x−1 Se x /MXene/carbonaceous nanoribbon heterostructure. As a result, the assembled Na/K full cells containing MXene-supported Fe x−1 Se x @carbonaceous anodes possess stable large-ion storage capabilities.

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