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Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I-III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

An amorphous hydrated vanadium oxide induced by Zn2+ intercalation is employed to serve as a high-performance cathode material for zinc-ion batteries.

A hybrid protective layer containing a Li3N/Li–Bi alloy on the Li surface is constructed to guide dendrite-free Li deposition by accelerating Li+ transport and homogenizing Li plating/stripping behavior.

Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones, and granular contents, such as myeloperoxidase (MPO) and elastase, which are released by neutrophils. Reactive oxygen species (ROS) are involved in NETs formation that promote tumor progress. Exenatide could downregulate ROS production in some cell types. However, it is unknown whether Exenatide could influence tumor progress through NETs. Here, we constructed the LLC-based lung cancer and MC38-based colon cancer models and found that Exenatide treatment decreased tumor infiltrated NETs and peripheral MPO-DNA complex and elastase. In addition, the in vitro study showed that Exenatide decreased NETs formation and release. Furthermore, flow cytometry analysis showed that Exenatide treatment reduced ROS production in tumor infiltrated and in vitro neutrophils. However, the ROS inhibitor DPI counteracted the decease of tumor infiltrated and in vitro NETs formation and release by Exenatide. Functionally, the Exenatide/αPD-1 combination therapy was superior to single therapy in restricting tumor growth. Removement of NETs by DNase I weaken the enhancement of αPD-1 treatment by Exenatide. The enriched tumor infiltrated, spleen and lymph node CD8

Background and Aims Soil heterogeneity can be caused by plant-soil feedback (PSF), but little is known about how such PSF-mediated soil heterogeneity affects plant growth and the distribution of roots. Moreover, as invasive and native plant species frequently differ in PSF and in root-foraging ability, they may also differ in their responses to PSF-mediated soil heterogeneity.Methods We first conditioned soils by 16 plant species (eight pairs of invasive alien and native species). Then, we grew each species in a homogeneous treatment with unconditioned soil and in three heterogeneous treatments with patches filled with two of the following three soils: unconditioned soil (control soil), soil conditioned by the target species (home soil) or soil conditioned by the other species in a pair (foreign soil).Results Invasive species were more negatively affected by the heterogeneous treatment with control-soil and home-soil patches than natives. In the heterogeneous treatment with home-soil and foreign-soil patches, root mass of the invasive species was much greater in the foreign-soil than in the home-soil patches, whereas the reverse was true for natives.Conclusion Although invasive species suffered more from conspecific PSF, root foraging allowed them to avoid home soil. In the long term, this could potentially help invasive species gain a competitive advantage over natives.

Supplementary Materials and Methods; Figure S1. Western blot of tropomyosin isoforms in neuroblastoma cells used in this project; Figure S2. Effect of combining tropomyosin and microtubule inhibitors on cell growth; Figure S3. A, B, Effect of TR100 or ATM-3507 in combination with paclitaxel in CHLA- 20 neuroblastoma cells; Figure S4. Cytotoxicity of CHLA-20 cells treated with different dosing regimens of TR100 plus VCR; Figure S5. Effect of combining TR100 and vincristine on tumor growth;Figure S6. Weights of animals from Fig. 4 and S5; Figure S7. The combination of tropomyosin inhibitors plus vincristine did not impact the microtubule network of cells in interphase; Figure S8. The combination of TR100 and paclitaxel induces apoptosis in CHLA-20 neuroblastoma cells; Table S1. IC50 concentrations for TR100 and ATM-3057 in a panel of neuroblastoma cell lines; Table S2. Pharmacokinetic analysis after single dosing of ATM3507/Dexolve intravenously at 30mg/kg in non-tumor bearing immunocompetent mice (Balb/C, n=3).

Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While antimicrotubule drugs are well-established, antiactin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other antitropomyosin analogues for anticancer and on-target activity using a series of in vitro cell-based and biochemical assays. ATM-3507 was selected as the new lead based on its ability to disable Tpm3.1-containing filaments, its cytotoxicity potency, and more favorable drug-like characteristics. We tested ATM-3507 and TR100 alone and in combination with antimicrotubule agents against neuroblastoma models in vitro and in vivo. Both ATM-3507 and TR100 showed a high degree of synergy in vitro with vinca alkaloid and taxane antimicrotubule agents. In vivo, combination-treated animals bearing human neuroblastoma xenografts treated with antitropomyosin combined with vincristine showed minimal weight loss, a significant and profound regression of tumor growth and improved survival compared with control and either drug alone. Antitropomyosin combined with vincristine resulted in G2–M phase arrest, disruption of mitotic spindle formation, and cellular apoptosis. Our data suggest that small molecules targeting the actin cytoskeleton via tropomyosin sensitize cancer cells to antimicrotubule agents and are tolerated together in vivo. This combination warrants further study. Mol Cancer Ther; 16(8); 1555–65. ©2017 AACR.

Video captioning aims to automatically describe a video clip with informative sentences. At present, deep learning-based models have become the mainstream for this task and achieved competitive results on public datasets. Usually, these methods leverage different types of features to generate sentences, e.g. semantic information, 2D or 3D features. However, some methods only treat semantic information as a complement of visual representations, and cannot fully exploit it; some of them ignore the relationship between different types of features. In addition, most of them select multiple frames of a video with an equally spaced sampling scheme, resulting in much redundant information. To address these issues, we present a novel video captioning framework, Semantic Enhanced video captioning with Multi-feature Fusion, SEMF for short. It optimizes the use of different types of features from three aspects. First of all, a semantic encoder is designed to enhance meaningful semantic features through a semantic dictionary to boost performance. Secondly, a discrete selection module pays attention to important features and obtains different contexts at different steps to reduce feature redundancy. Finally, a multi-feature fusion module uses a novel relation-aware attention mechanism to separate the common and complementary components of different features to provide more effective visual features for the next step. Moreover, the entire framework can be trained in an end-to-end manner. Extensive experiments are conducted on Microsoft Research Video Description Corpus (MSVD) and MSR-Video to Text (MSR-VTT) datasets. The results demonstrate that SEMF is able to achieve state-of-the-art results.

Video captioning aims to automatically generate natural language sentences describing the content of a video. Although encoder-decoder-based models have achieved promising progress, it is still very challenging to effectively model the linguistic behavior of human in generating video captions. In this paper, we propose a novel video captioning model by learning from g L obal s E ntence and looking A hea D , LEAD for short. Specifically, LEAD consists of two modules: a Vision Module (VM) and a Language Module (LM). Thereinto, VM is a novel attention network, which can map visual features to high-level language space and model entire sentences explicitly. LM can not only effectively make use of the information of the previous sequence when generating the current word, but also have a look at the future word. Therefore, based on VM and LM, LEAD can obtain global sentence information and future word information to make video captioning more like a fill-in-the-blank task than a word-by-word sentence generation. In addition, we also propose an autonomous strategy and a multi-stage training scheme to optimize the model, which can mitigate the problem of information leakage. Extensive experiments show that LEAD outperforms some state-of-the-art methods on MSR-VTT, MSVD and VATEX, demonstrating the effectiveness of the proposed approach in video captioning. In addition, we release the code of our proposed model to be publicly available 1 .

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

It has been suggested that establishment of one alien invader might promote further invasions. Such a so-called invasional meltdown could be mediated by differences in soil-legacy effects between alien and native plants. Whether such legacy effects might depend on the diversity of the invaded community has not been explored to date. Here, we conducted a two-phase plant-soil feedback experiment. In a soil-conditioning phase, we grew five alien and five native species as invaders in 21 communities of one, two or four species. In the subsequent test phase, we grew five alien and five native species on the conditioned soils. We found that growth of these test species was negatively affected by soils conditioned by both a community and an invader, and particularly if the previous invader was a conspecific (i.e. negative plant-soil feedback). Alien test species suffered less from soil-legacy effects of previous allospecific alien invaders than from the legacy effects of previous native invaders. However, this effect decreased when the soil had been co-conditioned by a multispecies community. Our findings suggest that plant-soil feedback-mediated invasional meltdown may depend on community diversity and therefore provide some evidence that diverse communities could increase resistance against subsequent alien invasions. published

Destruxin A (DA) is a mycotoxin secreted by entomogenous fungi, such as Metarhizium anisopliae, which has broad-spectrum insecticidal activity. Insect innate immunity provides resistance against the invasion of entomopathogenic fungi. Previous studies have shown that DA could inhibit the immune response, however, the suppressive mechanism of DA on prophenoloxidase system is still unknown.Based on the transcriptome of Aphis citricola, we screened the scavenger receptor class B(AcSR-B)and identified that it significantly responds to DA. Spatio-temporal expression analysis showed that AcSR-B is highly expressed in adult stage and is mainly distributed in the abdominal region. We further revealed that both M. anisopliae and Escherichia coli could suppress the expression of AcSR-B at 24 h, and that the expressed recombinant protein rAcSR-B possessed agglutination activity to M. anisopliae and E. coli. DA could suppress the protein expression of AcSR-B. In addition, RNA interference of AcSR-B caused death of A. citricola in a dose-dependent manner, and RNA interference of AcSR-B increased mortality in A. citricola under the same lethal concentration of DA. The inhibiting effect of AcSR-B silencing was similar with the DA treatment upon phenol oxidase (PO) activity of A. citricola hemolymph. DA could not decrease PO activity further after AcSR-B silencing.Destruxin A inhibits melanization by suppressing AcSR-B in A. citricola. Our findings are helpful in understanding the underlying molecular mechanism of the DA suppressing immune system, and uncover a potential molecular target for double-stranded RNA (dsRNA) insecticides.

Intracerebral hemorrhage (ICH) is a common neurological condition that causes severe disability and even death. Even though the mechanism is not clear, increasing evidence shows the efficacy of atorvastatin on treating ICH. In this study, we examined the impact of atorvastatin on the NOD-like receptor protein 3 (NLRP3) inflammasome and inflammatory pathways following ICH. Mouse models of ICH were established by collagenase injection in adult C57BL/6 mice. IHC mice received atorvastatin treatment 2 h after hematoma establishment. First, the changes of glial cells and neurons in the brains of ICH patients and mice were detected by immunohistochemistry and western blotting. Second, the molecular mechanisms underlying the microglial activation and neuronal loss were evaluated after the application of atorvastatin. Finally, the behavioral deficits of ICH mice without or with the treatment of atorvastatin were determined by neurological defect scores. The results demonstrated that atorvastatin significantly deactivated glial cells by reducing the expression of glial fibrillary acidic protein (GFAP), Ionized calcium binding adapter molecule 1 (Iba1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in ICH model mice. For inflammasomes, atorvastatin also showed its efficacy by decreasing the expression of NLRP3, cleaved caspase-1, and IL-1β in ICH mice. Moreover, atorvastatin markedly inhibited the upregulation of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88), which indicated deactivation of NLRP3 inflammasomes. By inhibiting the activities of inflammasomes in glial cells, neuronal loss was partially prevented by suppressing the apoptosis in the brains of ICH mice, protecting them from neurological defects.

We propose an objective Mn-based competitive capacity evolution protocol and a recusing strategy for dead Mn-based Zn-ion batteries. The findings would provide new insights to understand the electrochemical behaviors more comprehensively.

Fine-grained hashing is a new topic in the field of hashing-based retrieval and has not been well explored up to now. In this paper, we raise three key issues that fine-grained hashing should address simultaneously, i.e., fine-grained feature extraction, feature refinement as well as a well-designed loss function. In order to address these issues, we propose a novel Fine-graIned haSHing method with a double-filtering mechanism and a proxy-based loss function, FISH for short. Specifically, the double-filtering mechanism consists of two modules, i.e., Space Filtering module and Feature Filtering module, which address the fine-grained feature extraction and feature refinement issues, respectively. Thereinto, the Space Filtering module is designed to highlight the critical regions in images and help the model to capture more subtle and discriminative details; the Feature Filtering module is the key of FISH and aims to further refine extracted features by supervised re- weighting and enhancing. Moreover, the proxy-based loss is adopted to train the model by preserving similarity relationships between data instances and proxy-vectors of each class rather than other data instances, further making FISH much efficient and effective. Experimental results demonstrate that FISH achieves much better retrieval performance compared with state-of-the-art fine-grained hashing methods, and converges very fast. The source code is publicly available: https://github.com/chenzhenduo/FISH.

Poly(ethylene glycol)dimethacrylate-added perovskite films can effectively regulate crystal growth, passivate defects, release strains and enhance the mechanical stability of PSCs.