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Abstract: Objective. : Icodextrin, a novel glucose polymer solution utilized for peritoneal dialysis, has been demonstrated to have prolonged intraperitoneal (IP) instillation volumes in comparison to standard PBS solutions. In an animal model of ovarian cancer, we explored whether a survival advantage exists utilizing icodextrin rather than PBS as a delivery solution for an infectivity enhanced virotherapy approach. Methods. : Initial experiments evaluated whether icodextrin would adversely affect replication of a clinical grade infectivity enhanced conditionally replicative adenovirus (Δ24-RGD). Virus was added to prepared blinded solutions of PBS or icodextrin (20%) and then evaluated in vitro in various human ovarian cancer cell lines (SKOV3.ip1, PA-1, and Hey) and in vivo in a SKOV3.ip1 human ovarian cancer IP murine model. Viral replication was measured by detecting adenovirus E4 gene levels utilizing QRT-PCR. Survival was subsequently evaluated in a separate SKOV3.ip1 ovarian cancer IP murine model. Cohorts of mice were treated in blinded fashion with PBS alone, icodextrin alone, PBS+Δ24-RGD, or icodextrin+Δ24-RGD. Survival data were plotted on Kaplan–Meier curve and statistical calculations performed using the log-rank test. Results. : There was no adverse affect of icodextrin on vector replication in the ovarian cancer cell lines nor murine model tumor samples evaluated. Median survival in the IP treated animal cohorts was 23 days for the PBS group, 40 days for the icodextrin group, 65 days for the PBS+Δ24-RGD group, and 105 days for icodextrin+Δ24-RGD (p =0.023). Of note, 5 of the 10 mice in the icodextrin+Δ24-RGD group were alive at the end of the study period, all without evidence of tumor (120 days). Conclusions. : These experiments suggest that the use of dialysates such as icodextrin may further enhance the therapeutic effects of novel IP virotherapy and other gene therapy strategies for ovarian cancer. Phase I studies utilizing icodextrin-based virotherapy for ovarian cancer are currently in development. [Copyright &y& Elsevier]

Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates paraspinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics. [ABSTRACT FROM AUTHOR]

Adenoviral vectors have a poor record of transgene delivery efficiency through physical barriers such as the epithelium or endothelium. We report here the construction of an adenoviral vector that has the capability to be transported across polarized epithelial monolayers of Caco-2 cells (a colon carcinoma cell line) by transcytosis. This transcytosis is transferrin receptor (TfR)-mediated with use of a bifunctional adaptor, soluble coxsackie adenovirus receptor (sCAR)-Tf, and is both temperature and iron dependent. Under experimental conditions, the adenoviral transcytosis was inhibited by pretreatment of Caco-2 cells with colchicine, an inhibitor of transcytosis, and was not enhanced by pretreatment with Brefeldin A (BFA), an enhancer of transcytosis. In these Caco-2 cells, the transcytosis rate was 0.3 ± 1.3% (SD). The transcytosed adenoviruses remain biologically functional. These data suggest the potential clinical benefit under conditions where drug delivery is a challenge, such as within the airway epithelium, at the bladder lumen urothelial cell interface, and across the blood–brain barrier for clinical treatment of lung, urogenital, and brain disorders, respectively, by adenoviral transcytosis of transgene delivery. [Copyright &y& Elsevier]

It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a “tumor on” and “liver off” profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.Cancer Gene Therapy (2004) 11, 256-262. doi:10.1038/sj.cgt.7700679 Published online 12 March 2004 [ABSTRACT FROM AUTHOR]

Oncolytic viruses that are replication competent in tumor but not in normal cells represent a novel approach for treating neoplastic diseases. However, the oncolytic potency of replicating agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy or virotherapy have been based on serotype 5 (Ad5). Unfortunately, expression of the primary receptor for Ad5 (the coxsackie–adenovirus receptor, or CAR) is highly variable on ovarian and other cancer cells. By performing genetic fiber pseudotyping, we created Ad5/3-Δ24, a conditionally replicating adenovirus that does not bind CAR but facilitates entry into and killing of ovarian cancer cells. We show replication of Ad5/3-Δ24 and subsequent oncolysis of ovarian adenocarcinoma lines. Replication was also analyzed with quantitative PCR on three-dimensional primary tumor cell spheroids purified from patient samples. Moreover, in a therapeutic orthotopic model of peritoneal carcinomatosis, dramatically enhanced survival was noted. Finally, Ad5/3-Δ24 achieved a significant antitumor effect as assessed by noninvasive, in vivo bioluminescence imaging. Therefore, the preclinical therapeutic efficacy of Ad5/3-Δ24 is improved over the respective CAR- and integrin-binding controls. Taken together with promising biodistribution and toxicity data, this approach could translate into successful clinical interventions for ovarian cancer patients. [Copyright &y& Elsevier]

Replication competent viruses hold promise for treatment of advanced cancers resistant to available therapeutic modalities. Although preliminary clinical results have substantiated their efficacy, preclinical development of these novel approaches is limited by assay substrates. The evaluation of candidate agents could be confounded by differences between primary tumor cells and tumor cell lines, as discordance in the levels of surface receptors relevant for viral entry has been reported. Since primary tumor cells are difficult to analyze ex vivo for longitudinal observation of virus replication, we developed three-dimensional aggregates or spheroids of unpassaged and purified ovarian cancer cells as a means for prolonging primary tumor cell viability and as a three-dimensional in vitro model for replicative viral infection. Ovarian cancer cells purified from ascites samples were sustained for 30 days while retaining the infection profile with tropism modified and unmodified adenoviruses (Ads). Cell line and primary cell spheroids were used to quantitate the replication and oncolytic potency of replicative Ads in preclinical testing for human ovarian cancer trials. Therefore, spheroids provide a method to sustain purified unpassaged primary ovarian cancer cells for extended periods and to allow evaluation of replicative viruses in a three-dimensional model.Cancer Gene Therapy (2003) 10, 377-387. doi:10.1038/sj.cgt.7700578 [ABSTRACT FROM AUTHOR]

The Co&z.sbnd;B amorphous alloy catalyst was prepared by chemical reduction of Co2+ ions with BH4− in aqueous solution. Its activity and selectivity were measured during the liquid phase hydrogenation of acetonitrile and the effects of various factors, such as the reaction time, acetonitrile concentration, hydrogen pressure, reaction temperature, and solvent, were investigated. The following results were obtained: (1) The maximum ethylamine yield of 69% was obtained at the total conversion of acetonitrile. (2) The acetonitrile hydrogenation was zero-order with respect to acetonitrile and first-order with respect to hydrogen. Meanwhile, the selectivity to ethylamine increased slightly with the increase of either hydrogen pressure or acetonitrile concentration. (3) Increased reaction temperature resulted in a great enhancement in the activity (the apparent activation energy was determined as 46 kJ/mol) but a slight decrease in the selectivity to ethylamine. (4) Addition of a little H2O may result in an increase in the activity. All these effects are discussed based on the reaction mechanism. In comparison with other Co-based catalysts, such as Raney Co, pure Co powder catalyst, and the crystallized Co&z.sbnd;B catalyst, the amorphous Co&z.sbnd;B catalyst exhibited much higher activity and better selectivity to ethylamine. Although Ni-based catalysts had higher activity, their poorer selectivity to ethylamine suggested that they were not suitable for the title reaction under the present conditions. Based on the reaction mechanism and various characterizations, including SAED, XRD, SEM, TEM, EXAFS, XPS, hydrogen chemisorption, and DSC, the promoting effects on the activity and selectivity of the Co&z.sbnd;B amorphous catalyst are discussed briefly by considering both the structural characteristics and the electronic interaction between the Co and the alloying B. [Copyright &y& Elsevier]

Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent premature abrogation of replication, may have been a partial reason. Improving the oncolytic potency of agents has been hampered by the inability to study host–vector interactions in immune-competent systems, since human serotype adenoviruses do not productively replicate in animal tissues. Therefore, approaches such as immunomodulation, which could result in sustained replication and subsequently increased oncolysis, have not been studied. Utilizing the osteocalcin promoter for restricting the replication of a canine adenovirus to dog osteosarcoma cells, we generated and tested the first nonhuman oncolytic adenovirus. This virus effectively killed canine osteosarcoma cells in vitro and yielded a therapeutic benefit in vivo. Canine osteosarcoma is the most frequent malignant disease in large dogs, with over 8000 cases in the United States annually, and there is no curative treatment. Therefore, immunomodulation for increased oncolytic potency could be studied with clinical trials in this population. This could eventually translate into human trials. [Copyright &y& Elsevier]

The undoped Ru–B and Cr-doped Ru–B(Ru–Cr–B) amorphous alloy catalysts in the form of ultrafine particles were prepared by chemical reduction with borohydride in aqueous solution. During the liquid phase glucose hydrogenation, the Ru–B amorphous alloy exhibited much higher activity than Ni– or Co–B amorphous catalysts, Raney Ni, and other Ru-based catalysts including the metallic Ru powders and the crystallized Ru–B alloy. In the presence of the Cr-dopant, the specific activity of the Ru–Cr–B amorphous alloy catalysts per gram of Ru (RHm) first increased and then decreased with the increase of the Cr-content, showing that the Cr-dopant had both the positive and negative effects on the activity of the Ru–B amorphous alloy. The optimum Cr-content (molar ratio between Cr and Cr+Ru) was determined as 3.3%. The positive effect of the Cr-dopant could be attributed to the formation of Cr2O3, resulting in the higher surface area owing to its dispersing effect. The negative effect of the Cr-dopant was mainly attributed to its effect on the intrinsic activity per square meter of catalyst (RHS). A possible explanation was the electronic interaction between the Ru atom and the Cr2O3, making Ru less electron-enriched in comparison with that in the undoped Ru–B amorphous alloy. Such less electron-enriched Ru active sites were favorable for the glucose adsorption but unfavorable for the competitive adsorption of hydrogen. Thus, the activity decreased because the glucose hydrogenation was first-order with respect to the hydrogen, but zero-order with respect to the glucose. [Copyright &y& Elsevier]

As a member of two-dimensional (2D) materials, MXene is an ideal reinforcement phase for modified polymers due to its large number of polar functional groups on the surface. However, it is still relatively difficult to modify any functional groups on the surface of MXene at present, which limits its application in enhancing some polymers. Herein, one-dimensional (1D) attapulgite (ATP) nanomaterials were introduced onto the surface of MXene to form ATP–MXene hybrids, which successfully improved the mechanical properties of the epoxy composites. ATP with appropriate content can increase the surface roughness of the MXene lamellae to obtain better interface interaction. Therefore, remarkable enhancement on the mechanical property was achieved by adding M02A025 (0.2 wt % MXene and 0.25 wt % ATP), which is the optimum composition in the hybrids for composite mechanical properties. Compared to neat epoxy, the tensile strength, flexural strength and critical stress intensity factor (KIC) of M02A025/epoxy are increased by 88%, 57%, and 195%, respectively, showing a high application prospect. [ABSTRACT FROM AUTHOR]

• The nanocomposite membranes with mixed filler and crosslinking agent were fabricated. • Combination of polyorganosilicon and SFGO improved overall performance of membrane. • Physicochemical stability of the modified membranes was highly improved. • More water uptake and less swelling was obtained simultaneously in modified membrane. • The PSP/PO-SF3 membrane showed better DMFC performance compared to pristine one. It is a challenge to simultaneously improve proton conductivity, methanol resistance and physicochemical stability of polymer electrolyte membranes (PEMs) used in direct methanol fuel cell (DMFC). In response to this situation, the crosslinked nanocomposite membranes are prepared by introducing polyorganosilicon with various functional groups and sulfonic groups functionalized graphene oxide (SFGO) to the sulfonated poly (ether ether ketone ketone) in this paper. Based on our knowledge, no such PEM materials have been designed and prepared by this method. Scanning electron microcopy images demonstrate that there are good compatibility and connectivity between the matrix and fillers. The combination of polyorganosilicon and SFGO significantly improves the comprehensive performance of membrane, including mechanical property, dimensional stability, proton conductivity, methanol resistance, selectivity, oxidative and hydrolytic stabilities, cell performance, etc. Especially, the nanocomposite membrane with 3 wt% SFGO shows the highest conductivity (0.074 S cm−1 at 25 °C) and lowest methanol diffusion coefficient (3.56 × 10−7 cm2 S−1), which result in the optimal selectivity (2.08 × 105 Ss cm−3). In addition, the maximum power density (73.76 mW cm−2) of the membrane with 3wt% SFGO is higher than that of commercial Nafion@ 117 (61.59 mW cm−2) under identical experimental conditions. These results indicate that the crosslinked nanocomposite membranes will be new alternative to substitute the expensive Nafion® 117 for DMFC application. [ABSTRACT FROM AUTHOR]

Video saliency detection, which suffers from the interference of complicated motion and complex background, aims at discovering the motion-related and the most noticeable object in a video sequence while maintaining the spatiotemporal consistency of saliency maps. We propose a video saliency detection approach by constructing the moving object properties, meaning that motion is in concurrence with a general object for detected regions. With the assistance of different key frame strategies, the consistency propagation, which is respectively conducted to refine the obtained results of motion saliency and object proposals to improve low-quality detections and avoid the excessive accumulation of errors, is orderly implemented through sparse reconstruction based on the constructed adjacent relationships. Meanwhile, by integrating the refined object proposals with the refined salient motion detection, a pixel-based fusion strategy is applied to locate the most trustworthy motion object regions and suppress detection noises, such as dynamic background and stationary objects. Moreover, a Bayesian fusion framework that incorporates the global features obtained using low-rank constraints is employed to further enhance the accuracy and global temporal consistency for the obtained initial motion object regions. Then based on the obtained priors of motion objects and background regions, the spatial saliency map is estimated using the geodesic distances transform to discover more complete and spatially salient motion objects. Finally, an energy optimization function is proposed to intuitively integrate multiple saliency clues (i.e., spatial saliency, global features, and motion objects) and generate the global spatiotemporal consistency saliency map. Experimental results on three different benchmark datasets demonstrate that the proposed method successfully infers video moving objects and extracts the most salient regions, outperforming the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Researchers recently developed new mid-test warning faking-mitigation procedures to address the faking issue found in personality tests. The use of warning messages may unexpectedly make faking on personality tests a more cognitively loaded task, resulting in a positive relationship between personality scores and cognitive ability. The primary purpose of the present research is to investigate the effect of a mid-test warning on the personality-cognitive ability relationship. Graduate school applicants at a large public university in China (n = 2032) went through a test-warning-retest procedure. A true experimental design was used wherein each participant received a mid-test warning or a control message randomly. Results indicated that the mid-test warning significantly lowered personality scores over retesting, whereas the control message had little impact on applicants. The mid-test warning, however, did not induce positive and significant correlations between measures of personality and cognitive ability. [ABSTRACT FROM AUTHOR]

It is an essential capability of indoor mobile robots to avoid various kinds of obstacles. Recently, multimodal deep reinforcement learning (DRL) methods have demonstrated great capability for learning control policies in robotics by using different sensors. However, due to the complexity of indoor environment and the heterogeneity of different sensor modalities, it remains an open challenge to obtain reliable and robust multimodal information for obstacle avoidance. In this work, we propose a novel multimodal DRL method with auxiliary task (MDRLAT) for obstacle avoidance of indoor mobile robot. In MDRLAT, a powerful bilinear fusion module is proposed to fully capture the complementary information from two-dimensional (2D) laser range findings and depth images, and the generated multimodal representation is subsequently fed into dueling double deep Q-network to output control commands for mobile robot. In addition, an auxiliary task of velocity estimation is introduced to further improve representation learning in DRL. Experimental results show that MDRLAT achieves remarkable performance in terms of average accumulated reward, convergence speed, and success rate. Moreover, experiments in both virtual and real-world testing environments further demonstrate the outstanding generalization capability of our method. [ABSTRACT FROM AUTHOR]

• A novel sensor array for different pathogens identification is proposed. • The platform based on diverse interactions between 2D-MOFs and peptides. • Various pathogens can be detected and discriminated in urine. • The procedure of this sensor array is very simple and fast with only ~15 min. Rapid and efficient identification of pathogen is indispensable in clinical diagnosis because of the extremely severe consequence induced by pathogens infection. Taking advantages of the various compositions of pathogen surfaces, in this work we have proposed a simple and rapid sensor array for different pathogens identification and discrimination based on two-dimensional metal–organic frameworks (2D-MOFs) conjugated with functional peptide. Owing to the outstanding physical and chemical properties, ultrathin 2D-MOFs can adsorb dye-labeled peptides and consequently quench the fluorescence quickly and efficiently. Nevertheless, in the presence of pathogens, the anionic surface and different bimolecular composition of pathogens will endow them to interact with the 2D-MOFs or peptides through the diverse non-specific interactions. Subsequently, the dye-labeled peptides can be released with a recovery of fluorescence intensity. Consequently, the sensor array can identify various pathogens rapidly and efficiently based on the distinct fluorescence response patterns. Moreover, experimental results reveal that this approach can discriminate different pathogens with 100% accuracy, even in urine or mixed samples, demonstrating its reliability and effectiveness in the complex biological samples. More importantly, the procedure of pathogens identification by using this sensor array is very fast with only ~ 15 min, indicating the great potential applications in the timely clinical treatments and reliable monitoring of infectious disease trends. [ABSTRACT FROM AUTHOR]

• This is one of the pioneer studies on pixel-wise HCC segmentation of large H&E-stained WSIs, which presents significant advantages over the traditional patch-wise segmentation methods. • Based on the idea of multi-task learning, we propose a novel hybrid architecture for pixel-wise HCC segmentation of H&E-stained WSIs, which directly performs segmentation on WSI patches and no longer relies on a classification model. • Based on the idea of model ensemble, two complementary models based on SKM and scSEM are designed, which can effectively extract feature representations from different spaces and scales. • Our proposed method achieves the state-of-the-art performance on a large H&E-stained WSI dataset and other two pathological datasets, which verifies its effectiveness and generalization ability. Hepatocellular carcinoma (HCC), as the most common type of primary malignant liver cancer, has become a leading cause of cancer deaths in recent years. Accurate segmentation of HCC lesions is critical for tumor load assessment, surgery planning, and postoperative examination. As the appearance of HCC lesions varies greatly across patients, traditional manual segmentation is a very tedious and time-consuming process, the accuracy of which is also difficult to ensure. Therefore, a fully automated and reliable HCC segmentation system is in high demand. In this work, we present a novel hybrid neural network based on multi-task learning and ensemble learning techniques for accurate HCC segmentation of hematoxylin and eosin (H&E)-stained whole slide images (WSIs). First, three task-specific branches are integrated to enlarge the feature space, based on which the network is able to learn more general features and thus reduce the risk of overfitting. Second, an ensemble learning scheme is leveraged to perform feature aggregation, in which selective kernel modules (SKMs) and spatial and channel-wise squeeze-and-excitation modules (scSEMs) are adopted for capturing the features from different spaces and scales. Our proposed method achieves state-of-the-art performance on three publicly available datasets, with segmentation accuracies of 0.797, 0.923, and 0.765 in the PAIP, CRAG, and UHCMC&CWRU datasets, respectively, which demonstrates its effectiveness in addressing the HCC segmentation problem. To the best of our knowledge, this is also the first work on the pixel-wise HCC segmentation of H&E-stained WSIs. [ABSTRACT FROM AUTHOR]

• Downregulated YELLOW-FRUITED TOMATO 1 allele alters fruit color of yft 1 mutant. • Insertion downregulated YFT1 allele due to aberrant splicing and ORF break at 5′UTR. • Downregulated YFT1 allele affects ethylene and carotenoid synthesis in yft1 mutant. • Deepened insight into molecular mechanism of fruit color formation in tomato. The yft1 tomato mutant has a yellow-fruited phenotype controlled by a recessive gene of YFT1 allele, which has been shown by map-based cloning to be a homolog of ETHYLENE INSENSITIVE 2 (EIN2). Genetic lesion of YFT1 allele in yft1 is attributed to a 573 bp DNA fragment (IF 573) insertion at 1,200 bp downstream of the transcription start site. Transcriptomic analysis revealed that YFT1 lesion resulted in 5,053 differentially expressed genes (DEGs) in yft1 pericarp compared with the M82 wild type cultivar. These were annotated as being involved in ethylene synthesis, chromoplast development, and carotenoid synthesis. The YFT1 lesion caused a reduction in its own transcript levels in yft1 and impaired ethylene emission and signal transduction, delayed chromoplast development and decreased carotenoid accumulation. The molecular mechanism underlying the downregulated YFT1 allele in yft1 was examined at both RNA and DNA levels. The IF 573 event appeared to introduce two negative regulatory sequences located at -272 to -173 bp and -172 to -73 bp in the YFT1 allele promoter, causing alterative splicing due to introduction of aberrant splicing sites, and breaking upstream open reading frames (uORF) structure in the 5'-UTR. Those results a new provided insight into molecular regulation of color formation in tomato fruit. [ABSTRACT FROM AUTHOR]

New methods for investigating human astrocytes are urgently needed, given their critical role in the central nervous system. Here we show that CD49f is a novel marker for human astrocytes, expressed in fetal and adult brains from healthy and diseased individuals. CD49f can be used to purify fetal astrocytes and human induced pluripotent stem cell (hiPSC)-derived astrocytes. We provide single-cell and bulk transcriptome analyses of CD49f+ hiPSC-astrocytes and demonstrate that they perform key astrocytic functions in vitro , including trophic support of neurons, glutamate uptake, and phagocytosis. Notably, CD49f+ hiPSC-astrocytes respond to inflammatory stimuli, acquiring an A1-like reactive state, in which they display impaired phagocytosis and glutamate uptake and fail to support neuronal maturation. Most importantly, we show that conditioned medium from human reactive A1-like astrocytes is toxic to human and rodent neurons. CD49f+ hiPSC-astrocytes are thus a valuable resource for investigating human astrocyte function and dysfunction in health and disease. • CD49f is a novel, reactivity-independent marker for human astrocytes • CD49f can be used to purify human fetal astrocytes and iPSC-derived astrocytes • CD49f+ hiPSC-astrocytes acquire an A1-like reactive state upon cytokine stimulation • CD49f+ A1-like reactive astrocytes are dysfunctional and toxic to neurons in vitro Barbar et al. identify CD49f as a novel surface marker expressed by human astrocytes that can purify hiPSC-astrocytes and primary fetal astrocytes. CD49f+ hiPSC-astrocytes respond to pro-inflammatory stimuli and become A1 reactive astrocytes, which are dysfunctional and secrete neurotoxic factors that induce apoptosis in human and rodent neurons. [ABSTRACT FROM AUTHOR]

Brittle stars are dominant species in diverse benthic communities. As a circumpolar ophiuroid, Ophiura sarsii is distributed from Arctic waters to north temperate zones. The subspecies O. sarsii vadicola is dominant in the benthic communities of the Sea of Japan and the Yellow Sea Cold Water Mass (YSCWM). It lives at the southernmost boundary of O. sarsii distribution. Little is known about the genetic relationships of the different O. sarsii populations. We studied the molecular diversity, genetic divergences and demographic changes among seven O. sarsii populations from the north Pacific to the Atlantic, and O. sarsii vadicola from the YSCWM using the mitochondrial cytochrome c oxidase subunit I gene (CO I). Based on COI data, three lineages were determined among the eight geographic populations. O. sarsii vadicola is an independent mitochondrial lineage that maintains its subspecies status based on Internal transcribed Spacer 2 (ITS 2) data. The differentiation between species and subspecies may have occurred in the Sea of Japan at 3.6 million years ago (Ma) during the late Pliocene. O. sarsii may have dispersed from the Pacific to the Atlantic Ocean since early Pleistocene (1.5–1.2 Ma). The expansion of the subspecies was likely coeval with transgressions events in the Yellow Sea during the late Pleistocene period (111.8–60.1 ka). Additional samples and molecular markers from different areas of the O. sarsii distribution will be needed to unravel the evolutionary history of this species. • The divergence between Ophiura sarsii and subspecies O. sarsii vadicola occurred at 3.6 Ma. • Pacific individuals of O. sarsii dispersed to Atlantic Ocean since early Pleistocene. • O. sarsii vadicola population expanded at 111.8–60.1 ka in the ancient Yellow Sea. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing partial RNA dependency. Comparisons of brain tissue and cerebrospinal fluid proteomes reveal biomarker candidates. Combining with 5xFAD mouse analysis, we determine 15 Aβ-correlated proteins (e.g., MDK, NTN1, SMOC1, SLIT2, and HTRA1). 5xFAD shows a proteomic signature similar to symptomatic AD but exhibits activation of autophagy and interferon response and lacks human-specific deleterious events, such as downregulation of neurotrophic factors and synaptic proteins. Multi-omics integration prioritizes AD-related molecules and pathways, including amyloid cascade, inflammation, complement, WNT signaling, TGF-β and BMP signaling, lipid metabolism, iron homeostasis, and membrane transport. Some Aβ-correlated proteins are colocalized with amyloid plaques. Thus, the multilayer omics approach identifies protein networks during AD progression. • Deep profiling of proteome and phosphoproteome in AD progression • Validation of protein alterations in two independent AD cohorts • Identification of Aβ-induced protein changes in AD and the 5xFAD mouse model • Prioritization of proteins and pathways in AD by multi-omics integration By mass spectrometry-based proteomics and integrated multi-omics, Bai et al. reveal novel proteins and molecular networks during Alzheimer's disease progression and validate the proteins in 5xFAD mice. Further comparisons of brain tissue and cerebrospinal fluid proteomes identify biomarker candidates. [ABSTRACT FROM AUTHOR]

• A controllable etching and in-situ oxidation strategy is employed. • A series of Co 3 O 4 embedded α-Co/Ni(OH) 2 hollow nanocages are fabircated. • Their composition can be adjusted by controlling the temperature and pH values. • The optimized product presents excellent supercapacitor performance. The rational design and controllable fabrication of functional heterostructure consisting of capacitive framework and insertion is recognized as an efficient strategy to develop electrode materials for enhanced supercapacitor performance. In this work, a controllable NaH 2 PO 2 etching and in-situ O 2 oxidation process is developed, and a series of Co 3 O 4 embedded α-Co/Ni(OH) 2 hollow nanocages are successfully constructed via metal-organic frameworks (ZIF-67) as template. The optimized heterostructure (α-Co/Ni(OH) 2 @Co 3 O 4 -70) effectively take the advantages of each component that rich electrolyte diffusion channels and abundant reaction active sites of α-Co/Ni(OH) 2 species, as well as excellent conductivity and stability of Co 3 O 4 species. Therefore, a high capacitance value of 1000 F g−1 at 1 A g−1 and excellent ratio performance of 74% capacitance retained from 1 A g−1 to 10 A g−1 is achieved. Meanwhile, the hybrid nanocages present an enhanced cycling stability of retaining its 72.34% original capacitance after 8000 charge-discharge cycles. Furthermore, the as-assembled α-Co/Ni(OH) 2 @Co 3 O 4 -70//AC device exhibits a high energy density of 23.88 W h kg−1 at a power density of 0.075 kW kg−1. [ABSTRACT FROM AUTHOR]

l A novel method (SGL-SVM) for tumor classification on two-class and multi-class tumor datasets. l Gene primary selection reduces the computational complexity of the selection largely. l Sparse group Lasso considers the group effect variables and select more effective feature genes. l We investigate different feature gene selection methods and classifiers on the results. l The proposed method has better performance than other methods. At present, with the in-depth study of gene expression data, the significant role of tumor classification in clinical medicine has become more apparent. In particular, the sparse characteristics of gene expression data within and between groups. Therefore, this paper focuses on the study of tumor classification based on the sparsity characteristics of genes. On this basis, we propose a new method of tumor classification—Sparse Group Lasso (least absolute shrinkage and selection operator) and Support Vector Machine (SGL-SVM). Firstly, the primary selection of feature genes is performed on the normalized tumor datasets using the Kruskal–Wallis rank sum test. Secondly, using a sparse group Lasso for further selection, and finally, the support vector machine serves as a classifier for classification. We validate proposed method on microarray and NGS datasets respectively. Formerly, on three two-class and five multi-class microarray datasets it is tested by 10-fold cross-validation and compared with other three classifiers. SGL-SVM is then applied on BRCA and GBM datasets and tested by 5-fold cross-validation. Satisfactory accuracy is obtained by above experiments and compared with other proposed methods. The experimental results show that the proposed method achieves a higher classification accuracy and selects fewer feature genes, which can be widely applied in classification for high-dimensional and small-sample tumor datasets. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/SGL-SVM/. [ABSTRACT FROM AUTHOR]

Insect growth regulators (IGRs) are attractive alternatives to chemical insecticides. Since it has been reported that secondary metabolites from actinomycetes show insecticidal activities against various insect pests, actinomycetes could be a potential source of novel IGR compounds. In the present study, insect juvenile hormone antagonists (JHANs) were identified from actinomycetes and their insect growth regulatory and insecticidal activities were investigated. A total of 363 actinomycetes were screened for their insect growth regulatory and insecticidal activities against Aedes albopictus and Plutella xylostella. Among them, Streptomyces sp. AN120537 showed the highest JHAN and insecticidal activities. Five antimycins were isolated as active compounds by assay-guided fractionation and showed high JHAN activities. These antimycins also exhibited significant insecticidal activities against A. albopictus , P. xylostella , F. occidentalis , and T. urticae. Moreover, dead larvae treated with these antimycins displayed morphological deformities that are similar to those of JH-based IGR-treated insects. This is the first report demonstrating that the insecticidal activities of antimycins resulted from their possible JHAN activity. Based on our results, it is expected that novel JHAN compounds potentially derived from actinomycetes could be efficiently applied as IGR insecticides with a broad insecticidal spectrum. Unlabelled Image • Streptomyces sp. AN120537 showed high JHAN and insecticidal activities. • Antimycins were isolated from the strain AN120537 as JHAN substances. • Antimycins showed high insecticidal activities against broad range of insect pests. • JHAN substances from actinomycetes could be exploited as effective IGR insecticides. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. Methods: Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3β) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3β, and the detection rates of plasma circGSK3β for ESCC were investigated. Results: We demonstrated that upregulated expression of circGSK3β was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3β promoted ESCC cell migration and invasion via direct interaction with GSK3β and inhibiting GSK3β activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3β expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively. Conclusions: CircGSK3β exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3β have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection. [ABSTRACT FROM AUTHOR]

Correction: Following publication of the original article [1], the authors reported that the number of genes overlaying the bar graph in Fig. 3A were incorrectly counted and inserted (i.e. including a title tile, and in inverse order). The corrected numbers are below and match with the listed genes supplied in Additional File: Table S2. [ABSTRACT FROM AUTHOR]

By disregarding the 'rain component' but keeping the 'non‐rain component' only, results reconstructed by the conventional morphological component analysis decomposition‐based rain removal algorithms lose a lot of detail information. On the basis of the limitation, an image fusion strategy is introduced to remove rain from a video. The final rain‐free frame is recovered by employing the fused coefficients and the fused dictionary. Experimental results demonstrate that the proposed method can efficiently remove rain streaks, while at the same time preserve more detail information. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations represent approximately 4-12% of EGFR mutations and are generally refractory to the 1st and 2nd generation EGFR tyrosine kinase inhibitors (TKIs). Development of effective therapies for patients with EGFRex20ins mutant non-small-cell lung carcinoma (NSCLC) represents a great unmet need. Preclinical models have shown that osimertinib is active in NSCLC harboring EGFRex20ins, while the antitumor activity of osimertinib remains to be evaluated in patients with EGFRex20ins mutations.Methods: Tumor genotyping was performed in 2316 Chinese NSCLC cases with targeted next generation sequencing (NGS) covering the whole exons of EGFR gene. The frequency and genetic characteristics of EGFRexon20ins mutations were analyzed. Furthermore, six patients with specific EGFRexon20ins mutations and receiving osimertinib 80 mg once daily were retrospectively included to assess the antitumor activity and safety of monotherapy osimertinib.Results: EGFRex20ins mutations were identified in 4.8% (53/1095) of EGFR mutant NSCLC and 2.3% (53/2316) of all NSCLC cases. The most frequently identified EGFRexon20ins is A767_V769dup (17/53,32.1%). We found that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Four patients with osimertinib therapy achieved partial response and the rest stable disease. Median progression free survival (PFS) was 6.2 months (95% confidence interval 5.0-12.9 months; range 4.9-14.6 months). The most common adverse events (AEs) were diarrhea (2/6), pruritis (2/6), stomatitis (1/6) and nausea (1/6). No grade 3 or more AEs were documented.Conclusions: This study revealed that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Furthermore, our study firstly demonstrated promising antitumor activity of osimertinib in certain EGFRex20ins mutant advanced NSCLC patients, indicating that osimertinib treatment for EGFRex20ins positive patients deserves further study. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the authors reported two errors in the article. In the caption of Figure 1c the sentence "The 20 most highly upregulated EBV BART miRNAs identified between NPC specimens and normal nasopharyngeal mucosal specimens" should be corrected as "The highly upregulated EBV BART miRNAs identified between NPC specimens and normal nasopharyngeal mucosal specimens". [ABSTRACT FROM AUTHOR]

There is considerable interest in the development of antimicrobial polymers including dendrimers due to the ease of synthesis and low manufacturing cost compared to host defense peptides (HDPs). Herein, a new class of nanomaterials—lipidated amphiphilic dendrimers—is presented that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. Unlike conventional dendrimers that are prepared generation by generation symmetrically with molecular weight distribution, these lipidated dendrimers are prepared on the solid phase with a hanging lipid tail and precisely controlled structure. It is shown through rational design that these lipidated dendrimers display potent and selective antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, including multidrug‐resistant strains. In addition to antibacterial activity against planktonic bacteria, these dendrimers are also shown to inhibit bacterial biofilms effectively. This class of dendrimers as a new class of biomaterials may lead to a useful generation of antibiotic agents with practical applications. Asymmetriclipidated dendrimers are prepared on the solid phase with a hanging lipid tail and precisely controlled structure. Through rational design, these lipidated dendrimers display potent and selective antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, including multidrug‐resistant strains. In addition to antibacterial activity against planktonic bacteria, these dendrimers are also shown to inhibit bacterial biofilms effectively. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) is ubiquitously associated with nasopharyngeal carcinoma (NPC). EBV encodes two groups of microRNAs (miRNAs) which are divided into BamHI fragment H rightward open reading frame 1 (BHRF1) and BamHI-A rightward transcripts (BART) microRNAs. EBV miR-BART has been found to be involved in the development and progression of NPC. However, so far the role of EBV-miR-BART8-3p in NPC progression remains unknown. This study aimed to investigate the role of EBV-miR-BART8-3p in NPC and explore the underlying mechanisms. Methods: miRNA expression was profiled in NPC and normal nasopharyngeal mucosal specimens using miRNA sequencing. EBV-miR-BART8-3p and RNF38 expression was quantified with qPCR assay. The migration, invasion and metastasis of NPC cells were evaluated using CCK-8, colony-forming, wound-healing, and migration and invasion assays. The expression levels of epithelial-mesenchymal transition (EMT)-related markers,metastasis-related markers and NF-κB and Erk1/2 signaling proteins were determined using Western blotting. Tumorigenic assay was performed to evaluate the pulmonary metastatic ability of NPC cells in vivo. Results: EBV BART miRNAs were highly over-expressed and co-expressed in NPC and might be associated with deactivated immune response in NPC according to the sequencing analysis. EBV-miR-BART8-3p expression was significantly higher in human NPC specimens than in normal nasopharyngeal mucosal specimens. EBV-miR-BART8-3p was found to promote NPC migration, invasion and metastasis, drove an EMT process and upregulated expression of metastasis-related proteins expression in NPC cells. Our data showed EBV-miR-BART8-3p directly targeted RNF38 in NPC cells. Conclusion: The present study demonstrates that EBV-miR-BART8-3p plays a significant role in inducing EMT and promoting metastasis through directly targeting RNF38 in NPC cells via the activation of NF-κB and Erk1/2 signaling pathways. Our findings suggest that EBV-miR-BART8-3p is a potential therapeutic target for NPC. [ABSTRACT FROM AUTHOR]

A method is described for photoelectrochemical determination of chloramphenicol (CLOA). It is based on the use of (a) aptamers protected with photoactive WS2 nanosheets, and (b) DNase I-assisted target recycling. The DNA aptamer without label was employed for recognition of CLOA. In the absence of CLOA, the aptamer is adsorbed on the surface of WS2. This leads to a decrease of photocurrent due to the steric-hindrance effect of aptamer DNA. The adsorption of WS2 also protects the aptamer from digestion by DNase. In the presence of CLOA, the aptamer will be desorbed from the WS2 surface due to formation of an aptamer/CLOA conjugate. This results in an increased photocurrent due to a decreased amount of aptamer DNA on the electrode surface. The increase of photocurrent can be further improved by applying DNase triggered catalytic recycling of CLOA. Under optimal experimental conditions, the response is linear 10 pM - 10 nM CLOA concentration range, with a 3.6 pM lower detection limit (at 3σ). This method is acceptably selective, accurate and stable. It was applied to the determination of CLOA in spiked milk samples and gave satisfactory results.A simple and sensitive photoelectrochemical apta-biosensor was fabricated for chloramphenicol detection. In this work, WS2 nanosheets were employed as photoactive material, and DNase I catalytic chloramphenicol recycling strategy was adopted to amplify the detection signal. [ABSTRACT FROM AUTHOR]

Summary Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10 + GPR77 + CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10 + GPR77 + CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10 + GPR77 + CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10 + GPR77 + CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors. [ABSTRACT FROM AUTHOR]

An abstract of the article "Transcriptionally Targeting the Survivin Promoter to Human Gliomas," by Zeng B. Zhu, Winan J. Houdt, Yosef S. Haviv, Baogen Lu, Minghui Wang, Angel A. Rivera, Ilya V. Ulasov, Maciej S. Lesniak, Gene P. Siegal, Clemens M. F. Dirven and David T. Curiel is presented.