Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma.

Extracellular vesicles (EVs) have recently received increasing attention as essential mediators of communication between tumor cells and their microenvironments. Tumor-associated macrophages (TAMs) play a proangiogenic role in various tumors, especially head and neck squamous cell carcinoma (HNSCC), and angiogenesis is closely related to tumor growth and metastasis. This research focused on exploring the mechanisms by which EVs derived from TAMs modulate tumor angiogenesis in HNSCC. Our results indicated that TAMs infiltration correlated positively with microvascular density in HNSCC. Then we collected and identified EVs from TAMs. In the microfluidic chip, TAMs derived EVs significantly enhanced the angiogenic potential of pHUVECs and successfully induced the formation of perfusable blood vessels. qPCR and immunofluorescence analyses revealed that EVs from TAMs transferred miR-21-5p to endothelial cells (ECs). And targeting miR-21-5p of TAMs could effectively inhibit TAM-EVs induced angiogenesis. Western blot and tube formation assays showed that miR-21-5p from TAM-EVs downregulated LATS1 and VHL levels but upregulated YAP1 and HIF-1α levels, and the inhibitors of YAP1 and HIF-1α could both reduce the miR-21-5p enhanced angiogenesis in HUVECs. The in vivo experiments further proved that miR-21-5p carried by TAM-EVs promoted the process of tumor angiogenesis via YAP1/HIF-1α axis in HNSCC. Conclusively, TAM-derived EVs transferred miR-21-5p to ECs to target the mRNA of LATS1 and VHL, which inhibited YAP1 phosphorylation and subsequently enhanced YAP1-mediated HIF-1α transcription and reduced VHL-mediated HIF-1α ubiquitination, contributing to angiogenesis in HNSCC. These findings present a novel regulatory mechanism of tumor angiogenesis, and miR-21-5p/YAP1/HIF-1α might be a potential therapeutic target for HNSCC.

The antagonism mechanism of astilbin against cadmium-induced injury in chicken lungs via Treg/Th1 balance signaling pathway.

The purpose of this study was to investigate the effect of Treg/Th1 imbalance in cadmium-induced lung injury and the potential protective effect of astilbin against cadmium-induced lung injury in chicken. Cadmium exposure significantly decreased T-AOC and GSH-Px levels and SOD activity in the chicken lung tissues. In contrast, it significantly increased the MDA and NO levels. These results indicate that cadmium triggers oxidative stress in lungs. Histopathological analysis revealed that cadmium exposure further induced infiltration of lymphocytes in the chicken lungs, indicating that cadmium causes pulmonary damage. Further analysis revealed that cadmium decreased the expression of IL-4 and IL-10 but increased those of IL-17, Foxp3, TNF-α, and TGF-ß, indicating that the exposure of cadmium induced the imbalance of Treg/Th1. Moreover, cadmium adversely affected chicken lung function by activating the NF-kB pathway and inducing expression of genes downstream to these pathways (COX-2, iNOS), associated with inflammatory injury in the lung tissue. Astilbin reduced cadmium-induced oxidative stress and inflammation in the lungs by increasing antioxidant enzyme activities and restoring Treg/Th1 balance. In conclusion, our results suggest that astilbin treatment alleviated the effects of cadmium-mediated lung injury in chickens by restoring the Treg/Th1 balance.

A Finite Element Model for Predicting the Static Strength of a Composite Hybrid Joint with Reinforcement Pins.

This paper presents a finite element model for predicting the performance and failure behaviour of a hybrid joint assembling fibrous composites to a metal part with reinforcement micro pins for enhancing the damage tolerance performance. A unit-strip model using the cohesive elements at the bond interface is employed to simulate the onset and propagation of debonding cracks. Two different traction-separation laws for the interface cohesive elements are employed, representing the fracture toughness properties of the plain adhesive bond and a pin-reinforced interface, respectively. This approach can account for the large-scale crack-bridging effect of the pins. It avoids using concentrated pin forces in the numerical model, thus removing mesh-size dependency, and permitting more accurate and robust computational analysis. Lap joints reinforced with various pin arrays were tested under quasi-static load. Predicted load versus applied displacement relations are in good agreement with the test results, especially for the debonding onset and early stage of crack propagation.

Characteristics of sludge-based pyrolysis biochar and its application of enhancing denitrification.

A modified biochar for enhanced denitrification was developed through a facile pyrolysis method using sewage sludge as raw material and melamine as nitrogen source. Through electrochemical analysis, sludge-based pyrolysis biochar (SPBC) has superior electrical conductivity and poor redox activity. SPBC can increase the electron transfer through the geoconductor mechanism. The effect and the mechanism of SPBC on denitrification were studied. The nitrate treatment efficiency increased with the increase of SPBC dosage. From the perspective of molecular biology, the activities of NAR and NIR enzymes, the degradation efficiency of glucose and the ETSA of bacteria were all promoted with the increase of SPBC, thereby promoting the removal of NO3-. In addition, SPBC had a certain screening effect on microbial communities, and biodiversity decreased with the increase of SPBC dosage. Although the biodiversity decreased, the relative abundance of microorganisms conducive to denitrification increased with the increase of SPBC dosage. The transformation strategy of SPBC proposed in this paper provides a technical solution for sludge recycling and application for strengthening denitrification.

University-industry collaboration: The impact of postdoctoral workstations on labor investment efficiency.

This paper investigates whether managers use knowledge transferred from university-industry collaboration when making investment decisions on labor. To establish causality, we use a difference-in-difference method based on the staggered establishment of postdoctoral workstations in Chinese firms. We find that postdoctoral workstations enable managers to improve labor investment efficiency and thus help mitigate over- and under-investment problems in labor, and the higher the operational quality of the workstation, the more significant the increase in investment efficiency. This finding is robust to utilizing the event study approach, placebo test, propensity score matching, instrumental variable, and entropy balancing. Brain gain and knowledge transfer effects between universities and industries are two plausible mechanisms. Furthermore, the main effect is more pronounced for firms located closer to prestigious universities, firms are non-state-owned enterprises, human-capital-intensive, have political connections, and without national fellows' lead. Our findings suggest that brain gain in firms does not merely increase or reduce labor investments Per se, but rather inspires managers to maintain optimal labor levels through knowledge transfer processes.

Investigation of Adhesive Joining Strategies for the Application of a Multi-Material Light Rail Vehicle.

To meet the high demand for lightweight energy-efficient and safe structures for transport applications, a current state-of-the-art light rail vehicle structure is under development that adopts a multi-material design strategy. This strategy creates the need for advanced multi-material joining technologies. The compatibility of the adhesive with a wide range of material types and the possibility of joining multi-material structures is also a key advantage to its success. In this paper, the feasibility of using either epoxy or polyurethane adhesive joining techniques applied to the multi-material vehicle structure is investigated. Importantly, consideration is given to the effect of variation in bond thickness for both families of structural adhesives. Multi-material adhesively bonded single lap joints with different adhesives of controlled bond thicknesses were manufactured and tested in order to experimentally assess the shear strength and stiffness. The torsional stiffness and natural frequency of the vehicle were modelled using a global two-dimensional finite element model (FEM) with different adhesive properties, and the obtained vehicle performances were further explained by the coupon-level experimental tests. The results showed that the vehicle using polyurethane adhesive with a target bond thickness of 1.0 mm allowed for optimal modal frequency and weight reduction.

Fluorine-mediated synthesis of anisotropic iron oxide nanostructures for efficient T2-weighted magnetic resonance imaging.

Herein, we developed a novel strategy for the shape-controlled synthesis of iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent and dopant. The selective adsorption of fluoride ions onto the specified crystal planes of iron oxide nanocrystals leads to the formation of octapod nanoparticles (ONPs) and cubic nanocrystal clusters (CNCs). Both ONPs and CNCs present high r2 values (526.5 and 462.2 mM-1 s-1, respectively) due to the synergistic effect of a larger effective radius, clustering and fluorine doping. The in vivo MRI results show significant enhancement in T2-weighted images of the liver after the intravenous injection of ONPs and CNCs, suggesting their great potential as efficient T2-weighted MRI contrast agents. This new approach of achieving anisotropic fluorine-doped iron oxide nanostructures with high r2 relaxivity provides an alternative strategy for the development of highly sensitive T2 contrast agents for MRI.

Reactive Oxygen Species Accumulation Strongly Allied with Genetic Male Sterility Convertible to Cytoplasmic Male Sterility in Kenaf.

Male sterility (MS) plays a key role in the hybrid breed production of plants. Researchers have focused on the association between genetic male sterility (GMS) and cytoplasmic male sterility (CMS) in kenaf. In this study, P9BS (a natural GMS mutant of the kenaf line P9B) and male plants of P9B were used as parents in multiple backcross generations to produce P9SA, a CMS line with stable sterility, to explore the molecular mechanisms of the association between GMS and CMS. The anthers of the maintainer (P9B), GMS (P9BS), and CMS (P9SA) lines were compared through phenotypic, cell morphological, physiological, biochemical observations, and transcriptome analysis. Premature degradation of the tapetum was observed at the mononuclear stage in P9BS and P9SA, which also had lower activity of reactive oxygen species (ROS) scavenging enzymes compared with P9B. Many coexpressed differentially expressed genes were related to ROS balance, including ATP synthase, electron chain transfer, and ROS scavenging processes were upregulated in P9B. CMS plants had a higher ROS accumulation than GMS plants. The MDA content in P9SA was 3.2 times that of P9BS, and therefore, a higher degree of abortion occurred in P9SA, which may indicate that the conversion between CMS and GMS is related to intracellular ROS accumulation. Our study adds new insights into the natural transformation of GMS and CMS in plants in general and kenaf in particular.

Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy.

Precise manipulation of optical properties through the structure-evolution of plasmonic nanoparticles is of great interest in biomedical fields including bioimaging and phototherapy. However, previous success has been limited to fixed assembled structures or visible-NIR-I absorption. Here, an activatable NIR-II plasmonic theranostics system based on silica-encapsulated self-assembled gold nanochains (AuNCs@SiO2 ) for accurate tumor diagnosis and effective treatment is reported. This transformable chain structure breaks through the traditional molecular imaging window, whose absorption can be redshifted from the visible to the NIR-II region owing to the fusion between adjacent gold nanoparticles in the restricted local space of AuNCs@SiO2 triggered by the high H2 O2 level in the tumor microenvironment (TME), leading to the generation of a new string-like structure with strong NIR-II absorption, which is further confirmed by finite-difference-time-domain (FDTD) simulation. With the TME-activated characteristics, AuNCs@SiO2 exhibits excellent properties for photoacoustic imaging and a high photothermal conversion efficiency of 82.2% at 1064 nm leading to severe cell death and remarkable tumor growth inhibition in vivo. These prominent intelligent TME-responsive features of AuNCs@SiO2 may open up a new avenue to explore optical regulated nano-platform for intelligent, accurate, and noninvasive theranostics in NIR-II window.

Comparative Transcriptome Analysis between a Novel Allohexaploid Cotton Progeny CMS Line LD6A and Its Maintainer Line LD6B.

Cytoplasmic male sterility (CMS) is an important agronomic feature and provides an effective tool for heterosis utilization of crops. This study reports the comparative transcriptomic sketches between a novel allohexaploid cotton progeny CMS line LD6A and its maintainer line LD6B using de novo transcriptome sequencing technology at the pollen abortion stage. A total of 128,901 Unigenes were identified, in which 2007 were upregulated and 11,864 were downregulated. The significantly differentially expressed genes (DEGs) in LD6A show a distant and diverse genetic nature due to their distant hybrid hexaploidy progeny. Further analysis revealed that most of the DEGs participated in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, histone acetyltransferase activity, sepal development, stigma development, cotyledon development and microsporogenesis. A highly differentially expressed toxic protein, Abrin, was identified in the CMS line LD6A, which can catalyze the inactivation of ribosomes and consequently lead to cell death through the mitochondrial pathway in human cells. Twelve DEGs were selected randomly to validate transcriptome data using quantitative reverse-transcribed PCR (qRT-PCR). This study will contribute to new ideas and foundations related to the molecular mechanism of CMS and the innovation of cotton germplasm resources.

Synthesis Of PEG-Coated, Ultrasmall, Manganese-Doped Iron Oxide Nanoparticles With High Relaxivity For T1/T2 Dual-Contrast Magnetic Resonance Imaging.

BACKGROUND: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. METHODS: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. RESULTS: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. CONCLUSION: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.

Fluorine-assisted structural engineering of colloidal anatase TiO2 hierarchical nanocrystals for enhanced photocatalytic hydrogen production.

Anatase TiO2 materials are well-known for their photocatalytic properties and their structure-performance relationship has been intensively studied over the past few decades. In this study, we report a versatile strategy to control the geometric and electronic structure of hierarchical anatase TiO2 nanocrystals via a colloidal synthesis technique in order to optimize their photocatalytic performances. The synthesis is modified from a classical nonaqueous sol-gel approach in which titanium alkoxides and long carbon chain carboxylic acids are used as titanium sources and hydrolysis/capping agents, respectively. By introducing fluoride ions into the reaction as competitive capping agents and controlling other parameters, the geometric structure of TiO2 nanocrystals can be regulated from nanorods and nanobipyramids to their hierarchical assembly structures with controlled dimension and crystallinity. Meanwhile, it is confirmed that the fluoride capping agents also affect the surface structure of TiO2 by fluorine doping, which exerts an additional impact on the electronic structure of TiO2 nanocrystals apart from morphology variation. Further investigation of photocatalytic hydrogen production performances of TiO2 nanocrystals with different structures indicates that the catalytic efficiency is highly dependent on structural factors including hierarchical shape, surface area and doping status. Obvious improvement of photocatalytic performance is observed in the optimized hierarchical TiO2 nanocrystals (2033.6 µmol g-1 h-1) compared to that in commonly prepared TiO2 nanobipyramids (1135.5 µmol g-1 h-1) and other hierarchical TiO2 nanocrystals (1331.9 µmol g-1 h-1 or lower), which demonstrates the effectiveness of material optimization by the strategy developed in this study.

Comparative Transcriptome Analysis Reveals the Cause for Accumulation of Reactive Oxygen Species During Pollen Abortion in Cytoplasmic Male-Sterile Kenaf Line 722HA.

Cytoplasmic male sterility (CMS) is a maternally inherited trait used for hybrid production in plants, a novel kenaf CMS line 722HA was derived from the thermo-sensitive male-sterile mutant 'HMS' by recurrent backcrossing with 722HB. The line 722HA has great potential for hybrid breeding in kenaf. However, the underlying molecular mechanism that controls pollen abortion in 722HA remains unclear, thus limiting the full utilization of this line. To understand the possible mechanism governing pollen abortion in 722HA, cytological, transcriptomic, and biochemical analyses were carried out to compare the CMS line 722HA and its maintainer line 722HB. Cytological observations of the microspore development revealed premature degradation of the tapetum at the mononuclear stage, which resulted in pollen dysfunction. The k-means clustering analysis of differentially expressed genes (DEGs) revealed that these genes are related to processes associated with the accumulation of reactive oxygen species (ROS), including electron transport chain, F1F0-ATPase proton transport, positive regulation of superoxide dismutase (SOD), hydrogen peroxide catabolic, and oxidation-reduction. Biochemical analysis indicated that ROS-scavenging capability was lower in 722HA than in 722HB, resulting in an accumulation of excess ROS, which is consistent with the transcriptome results. Taken together, these results demonstrate that excessive ROS accumulation may affect the normal development of microspores. Our study provides new insight into the molecular mechanism of pollen abortion in 722HA and will promote further studies of kenaf hybrids.

Migration of Iron Oxide Nanoparticle through a Silica Shell by the Redox-Buffering Effect.

This study demonstrates that mineral redox buffer, an important concept in geology, can be used to manipulate the migration of nanoparticles and produce nanostructures of unexpected morphologies. Using a silica shell as a redox buffer, we show that iron oxide nanoparticles can be relocated from inside to the outer surface of the silica shell. The migration of iron oxide through silica was initiated by manipulation of the oxygen fugacity conditions at an elevated temperature. During the treatment, iron oxide was absorbed and then separated from the silica shell by the formation and then decomposition of iron silicate (Fe2SiO4). Tuning the relative dimensions of the iron oxide core and silica shell allows control of the shape of the iron oxide-silica composite structures. It is believed that the discovery of the nanoscale redox buffering effect can be extended to control the morphological configuration of other multivalent metal oxide nanocomposite structures by this particular type of template synthesis through manipulation of the chemical-transport properties of nanoscale templates.

Comparative Analysis of the Cytology and Transcriptomes of the Cytoplasmic Male Sterility Line H276A and Its Maintainer Line H276B of Cotton (Gossypium barbadense L.).

In this study, the tetrad stage of microspore development in a new cotton (Gossypium barbadense L.) cytoplasmic male sterility (CMS) line, H276A, was identified using paraffin sections at the abortion stage. To explore the molecular mechanism underlying CMS in cotton, a comparative transcriptome analysis between the CMS line H276A and its maintainer line H276B at the tetrad stage was conducted using an Illumina HiSeq 4000 platform. The comparison of H276A with H276B revealed a total of 64,675 genes, which consisted of 59,255 known and 5420 novel genes. An analysis of the two libraries with a given threshold yielded a total of 3603 differentially expressed genes (DEGs), which included 1363 up- and 2240 down-regulated genes. Gene Ontology (GO) annotation showed that 2171 DEGs were distributed into 38 categories, and a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 2683 DEGs were classified into 127 groups. Thirteen DEGs were randomly selected and detected by quantitative reverse-transcribed PCR (qRT-PCR), and the results indicated that the transcriptome sequencing results were reliable. The bioinformatic analysis results in conjunction with previously reported data revealed key DEGs that might be associated with the male sterility features of H276A. Our results provide a comprehensive foundation for understanding anther development and will accelerate the study of the molecular mechanisms of CMS in cotton.

Correlation between social proximity and mobility similarity.

Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

High-yield halide-free synthesis of biocompatible Au nanoplates.

We communicate an unconventional synthesis of Au nanoplates with high yield and excellent reproducibility through polyvinylpyrrolidone (PVP)-assisted H2O2 reduction. Unlike the ones prepared using halide-based surfactants, the PVP-capped Au nanoplates are found to afford fairly easy bio-functionalization, suggesting a vastly expanded spectrum of applications in bio-related fields.

Magnetically tunable colloidal micromirrors.

Herein we demonstrate a method for decorating highly reflective 2D gold microplates with magnetic nanoparticles to produce an optical colloid that can be actuated using an applied magnetic field. These magnetic micromirrors can be rapidly rotated and exhibit a strong contrast in reflectance between the "on" and "off" states.

Stabilization of ultrafine metal nanocatalysts on thin carbon sheets.

A novel strategy was proposed to anchor ultrafine metal nanoparticles (NPs) on thin carbon sheets for highly stable and efficient heterogeneous catalysts. In this facile approach, a dense monolayer of ultrafine AuNPs was sandwiched between a silica core and a resin shell, followed by carbonization of the shell at a high temperature and then selective removal of the silica core. The shrinkage of the shells during carbonization facilitates partial embedment of the AuNPs on the carbon shell surface and provides superior stability against particle sintering during high temperature/mechanical post-treatments and catalytic reactions. It was also found that diffusion of reactants to the surface of AuNPs could be maximized by reducing the thickness of the hollow shells or simply by cracking the shells into thin carbon sheets, both significantly benefiting the catalytic efficiency. The advantages of this ultra-stable architecture together with the densely dispersed catalytic sites were demonstrated by their high stability and superior catalytic activity in reducing hydrophilic 4-nitrophenol and hydrophobic nitrobenzene.

Seed-Mediated Growth of Anatase TiO2 Nanocrystals with Core-Antenna Structures for Enhanced Photocatalytic Activity.

We demonstrate that anatase TiO2 nanocrystals composed of a nanocrystal core and nanorod antennas can be produced via a nonaqueous colloidal seed-mediated growth method. Anatase TiO2 nanocrystals with defined morphologies were first prepared as seeds, and then secondary anatase TiO2 nanorods were grown on the defined facets of the seeds under appropriate conditions. Systematic studies on the growth mechanism reveal that the formation of core-antenna nanocrystals involves an epitaxial growth process with specific orientational preference governed by both thermodynamic and kinetic factors. By manipulating the reaction conditions including the precursor amount and introduction rate, the epitaxial growth behavior can be well controlled. By further varying the morphology of seed nanocrystals, we have also been able to produce core-antenna anatase TiO2 nanocrystals with complex spatial configurations in a highly predictable manner. The high structural configurability and predictability offered by this seed-mediated growth method may provide great opportunities in enhancing the performance of TiO2-based nanostructures in many energy-related applications. As a demonstration, we show by simply manipulating the core-antenna structures that the photocatalytic activity of the anatase nanocrystals can be improved from the relatively less active seed nanocrystals or pure nanorods to the extent that exceeds the activity of the commercial P25 titania.