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Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through

Summary Although advances in coating technologies have allowed us to match—or even exceed—the lubricity of Nature’s low-friction surfaces, the performance of synthetic materials inevitably diminishes over time as the surfaces are worn and damaged by irreversible breakage of covalent bonds. Synthetic systems lack the bespoke repair mechanisms that replenish hydration lubrication surfaces in Nature. Here, we demonstrate dynamic repair of low-friction surfaces prepared through a surface-selective self-assembly strategy. Monolayers of lubricating polymers associate with functionalized surfaces through strong and specific host–guest interactions, leading to hydration lubrication surfaces with low coefficients of friction (0.024–0.028). Following friction-induced dissociation of the polymers, the polymer-to-surface interaction is restored by the reformation of host–guest complexes, thus repairing the monolayer, renewing the lubricity, and reducing the effects of wear. Such dynamically restored low-friction materials will be an essential tool in decreasing global energy use—a fifth of which is expended overcoming friction.

Surface contact with virus is ubiquitous in the transmission pathways of respiratory diseases such as Coronavirus Disease 2019 (COVID-19), by which contaminated surfaces are infectious fomites intensifying the transmission of the disease. To date, the influence of surface wettability on fomite formation remains elusive. Here, we report that superhydrophobicity prevents the attachment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces by repelling virus-laden droplets. Compared to bare surfaces, superhydrophobic (SHPB) surfaces exhibit a significant reduction in SARS-CoV-2 attachment of up to 99.99995%. We identify the vital importance of solid-liquid adhesion in dominating viral attachment, where the viral activity (N) is proportional to the cube of solid-liquid adhesion (A), N ∝ A3. Our results predict that a surface would be practically free of SARS-CoV-2 deposition when solid-liquid adhesion is ≤1 mN. Engineering surfaces with superhydrophobicity would open an avenue for developing a general approach to preventing fomite formation against the COVID-19 pandemic and future ones.

Alternative splicing (AS) is an essential post-transcriptional regulation mechanism for sex differentiation and gonadal development, which has rarely been reported in marine invertebrates. Sea cucumber (Apostichopus japonicus) is an economically important marine benthic echinoderm with a potential XX/XY sex determination mechanism, whose molecular mechanism in the gonadal differentiation has not been clearly understood. In this study, we analyzed available RNA-seq datasets of male and female gonads to explore if AS mechanism exerts an essential function in sex differentiation and gonadal development of A. japonicus. In our results, a total of 20,338 AS events from 7219 alternatively spliced genes, and 189 sexually differential alternative splicing (DAS) events from 156 genes were identified in gonadal transcriptome of sea cucumber. Gene Ontology analysis indicated that these DAS genes were significantly enriched in spermatogenesis-related GO terms. Maximal Clique Centrality (MCC) was then applied for protein-protein interaction (PPI) analysis to search for protein interactions and hub DAS gene. Among all DAS genes, we identified 10 DAS genes closely related to spermatogenesis and (or) sperm motility and a hub gene dnah1. Thus, this study revealed that alternative isoforms were generated from certain genes in female and male gonads through alternative splicing, which may provide direct evidence that alternative splicing mechanisms participate in female and male gonads. These results suggested a novel perspective for explaining the molecular mechanisms underlying gonadal differentiation between male and female sea cucumbers.

Methamphetamine (Meth), a highly addictive drug, can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. Meth's effects on modulating microglial neuroimmune functions and eliciting neuroinflammation have attracted considerable attention in recent years. Recent evident of the effect of the non-dependent domain containing adaptor inducing interferon (TRIF)/Pellino1 (Peli1) signaling axis on pro-inflammatory cytokine production provides novel clues for inflammation. Therefore, our study investigated Meth-induced neurotoxicity from a neuropathological perspective by examining TLR4-TRIF-Peli1 axis signaling activation. Meth significantly activated microglia accompanied by marked increase of TLR4 and TRIF expression, NF-kB and MAPK pathways activation and the production of IL-1β, TNF-α and IL-6. Peli1 was involved in Meth-mediated neuroinflammation and knockdown of Peli1 strongly reversed NF-kB and MAPK pathways activation and pro-inflammatory cytokine excretion. Intriguingly, Peli1 upregulation induced by Meth was dependent on TRIF rather than the myloid differentiation factor 88 (MyD88) pathway, since the silencing of TRIF significantly suppressed Meth-induced Peli1 upregulation, while MyD88 knockdown had no obvious impact. Additionally, an in vivo study verified TLR4-TRIF-Peli1 axis activation and an enhanced level of downstream cytokine expression in the cortex after Meth treatment. Therefore, these findings provide new insight regarding the specific contributions of the TRIF-Peli1 pathway to Meth-mediated neuroinflammation.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products. Toxicological studies have indicated that OPEs may affect male reproductive health, but human evidence is inconclusive. In this study, we explored associations of individual and mixtures of OPE exposure with semen quality among 1015 Chinese men from an infertility clinic. After adjusting for potential confounders, we observed that higher diphenyl phosphate (DPHP) and [Bis(2-methylphenyl) phosphate (BMPP)] exposure was associated with increased odds ratios (ORs) of having below-reference total sperm count. Higher bis (2-butoxyethyl) phosphate (BBOEP) exposure was associated with increased ORs of having below-reference progressive motility and total motility. For semen quality parameters modeled as continuous outcomes, inverse associations with individual OPE were still observed. In addition, urinary 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) concentrations were inversely associated with the percentage of normal morphology while positively associated with the percentage of abnormal heads. Quantile g-computation regression analyses showed that exposure to higher OPE mixtures was associated with lower total sperm motility and normal morphology. Our results indicated that both individual and mixtures of OPE exposure were associated with reduced semen quality.

Norovirus (NoV), a major food-borne virus, causes non-bacterial acute gastroenteritis in humans. Berries are generally harvested from low-growing bushes by hand and are minimally processed before being sold to consumers. Therefore, the consumption of berries has been linked to numerous food-borne gastroenteritis outbreaks caused by NoV in many countries. We performed a survey of NoV contamination in commercial fresh/frozen berry fruits collected from 2016 to 2017 in the Heilongjiang Province, the main berry-producing area in China, using a TaqMan-based real-time reverse transcription-PCR assay. Among 900 frozen and 900 fresh domestic retail berry samples, the prevalence of NoV was 9% (81/900) and 12.11% (109/900), including 35.80% (29/81) and 29.36% (32/109) of genotype GI alone, 54.32% (44/81) and 60.55% (66/109) of GII alone, and 9.88% (8/81) and 10.09% (11/109) of both GI and GII, respectively. No NoV was detected among the 677 frozen berry samples for export. Thus, the occurrence of NoV contamination was significantly higher in domestic berries than in exported berries and higher in fresh berries than in frozen berries. This study highlights the need for further risk surveillance for NoV contamination in berries produced in the Heilongjiang Province and recommends region-extended monitoring of retail berries for NoV.

Subgroup K avian leukosis virus (ALV-K) is a new subgroup of avian leukosis virus (ALV) first identified in Chinese indigenous chickens in recent years. In this study, an ALV-K strain was isolated from Luhua chicken in Shandong province, China, and designated SD20LH01. The full-length genomic sequence of SD20LH01 was 7491 bp, which had the highest homology with ALV-K reference strains GDFX0601, GDFX0602 and GDFX0603. The nucleotide homology of env gene of SD20LH01 with reference strains of subgroup A, B, C, D, E, and J was ranged from 57.1 to 93.2%, while 94.1 to 99.4% with other ALV-K reference strains. The nucleotide difference of SD20LH01 mainly clustered with gp85 gene and U3 sequence when compared with the reference strain of ALV-K. In order to investigate the pathogenicity of SD20LH01, SPF chicken embryos were infected by yolk sac inoculation, and 1-day-old chickens were infected by intraperitoneal inoculation of SD20LH01. The results showed that yolk sac inoculation of SD20LH01 could induce persistent viremia, growth retardation and reduce the immune response to NDV and AIV-H9 vaccines. However, intraperitoneal inoculation in 1-day-old chickens could only induce a low level of viremia. In addition, no tumors were found in infected chickens during the animal experiments. This study enriched the genomic sequence data of ALV-K isolated in Chinese indigenous chickens, and laid a foundation for further study on the pathogenesis and prevention of ALV-K.

The present study examined the associations of polycyclic aromatic hydrocarbon (PAH) exposure with metabolic syndrome (MetS) and its components. Data were from 5181 US adults recruited in the National Health and Nutrition Examine Survey 2001-2012. Environmental PAH exposure was estimated as concentrations of urinary PAH metabolites. Weighted quantile sum (WQS) regression and modified Poisson regression were separately conducted to estimate the associations of mixed and single PAH metabolites with MetS and its components. WQS regression analyses showed that participants with higher mixed PAH exposure had increased prevalence of MetS (prevalence ratio, 1.12; 95 % confidence interval, 1.06, 1.19), elevated waist circumference (1.07; 1.02, 1.12), elevated fasting blood glucose (1.07; 1.00, 1.14), elevated triglycerides (1.19; 1.09, 1.30), and reduced high-density lipoprotein cholesterol (1.11; 1.03, 1.20). In the models for single PAH metabolites, higher levels of 1-hydroxynaphthalene (1.15; 1.00, 1.32), 2-hydroxynaphthalene (1.20; 1.05, 1.38), 1-hydroxyphenanthrene (1.18; 1.04, 1.34), 2-hydroxyphenanthrene (1.38; 1.22, 1.57), and 1-pyrene (1.19; 1.05, 1.34) were respectively associated with increased prevalence of MetS (highest tertile vs lowest tertile). In addition, linear trends were noted for the associations of these PAH metabolites with MetS (all P for linear association ≤0.047). Smokers, drinkers, and participants with poor diet quality showed stronger associations between certain PAH metabolite with MetS. The findings suggest that the prevalence of MetS and its components increases when PAH exposure is at a high level, and that lifestyle factors, such as cigarette smoking, alcohol consumption, and diet quality, could modify the positive associations of certain PAH exposure with MetS.

A rational solvothermal method is proposed to achieve the conversion from a Zn contented metal organic framework to ZnO mesoporous single-crystal-like spheres. The as-prepared ZnO sphere is composed of oriented assembled primary crystals, which exhibits single crystal nature with narrow pore size distribution and high surface area. In addition, time depending trails indicate the metal organic framework functions as reservoir to control the release of Zn species and the organic molecules also serve as directing regent to facilitate the oriented assembling of the ZnO primary units. Thanks to this structure coherence, the ZnO sphere delivers high electron mobility, which enables reduced carrier recombination and improved collection efficiency of the photoelectrons when used as photoanode in CdS/CdSe sensitized solar cell. The device achieves a high power conversion efficiency of ∼6.20%, which is substantially improved from that of regular ZnO nanoparticles (∼5.02%). Moreover, when evaluated as anode for lithium ion battery, the ZnO sphere based electrode demonstrates high reversible capacity of 1016.7 mA h g−1 at 100 mA g−1 after 100 cycles, and excellent high rate stability which shows impressive reversible capacity of 698.4 mA h g−1 at 1000 mA g−1 after 300 cycles.

In this study, an antigen-capturing enzyme-linked immunosorbent assay (AC-ELISA) was established for the detection of avian reticuloendotheliosis virus (REV) using monoclonal and polyclonal antibodies against gp90. New Zealand white rabbits were immunized with recombinant REV-gp90 protein, and polyclonal antibodies were obtained after purification and used as the capture antibody. Mice monoclonal antibody 1A12D against REV-gp90 protein previously prepared in our laboratory was used as the detection antibody. The specificity of the AC-ELISA was confirmed with REV, avian leukosis virus subgroup J, Marek's disease virus serotype Ⅰ, avian hepatitis E virus and Fowl adenovirus serotype 4. The results showed that the AC-ELISA had specific binding reaction with REV, and did not react with other viruses. The detection limit of this assay was 195 TCID

Bolting, which is a serious problem during lettuce (Lactuca sativa L.) production, is responsible for substantial annual yield and quality losses. Gibberellin plays a critical role in the regulation of lettuce bolting. Additionally, DELLA proteins negatively regulate the gibberellin signaling pathway. However, it is unclear if DELLA proteins are involved in the regulation of lettuce bolting. Therefore, in this study, we identified four DELLA-encoding genes in lettuce, including LsRGL1, which was highly expressed in the stem and negatively correlated with bolting. Knocking down this gene in lettuce promoted bolting, whereas its overexpression inhibited bolting and the biosynthesis of gibberellin and auxin. A transcriptome analysis revealed that genes involved in gibberellin and auxin biosynthesis and flowering were affected in the LsRGL1-overexpressing lines. The yeast two-hybrid and yeast one-hybrid assay results indicated that LsRGL1 can interact with LsGA3ox and the LsYUC4 promoter region. Considered together, the results of this study suggest LsRGL1 negatively regulates lettuce bolting. Furthermore, its function may depend on modifications to gibberellin and auxin levels mediated at the transcript and protein levels.

We establish that stock liquidity is conducive to less corporate diversification. Two potential channels are identified: the financial constraint channel and the corporate governance channel. Specifically, the negative effect of liquidity on diversification is stronger among financially-constrained firms, since higher liquidity helps firms improve external capital markets and thus reduces the need to broaden the internal capital markets through diversification. Moreover, the effect of liquidity on diversification is strengthened among firms with severe information asymmetry, since enhanced price informativeness caused by increased liquidity promotes market monitoring and deters managers’ opportunistic diversification decisions. Meanwhile, we rule out the alternative explanation that liquidity discourages diversification by facilitating blockholders’ monitoring on managers’ decisions. Our results suggest that stock liquidity plays a positive role in corporate decision making.

In theory, discretionary pricing improves the company's performance by allowing managers to incorporate local information into their pricing decisions. However, in practice, managers are vulnerable to behavioral biases that can lead to inaccurate estimation of the customer's willingness to pay and price sensitivity, and precipitate poor decisions. This paper investigates the effectiveness of discretionary pricing and examines how information advantage and behavioral bias influence managers' pricing decisions. Collaborating with a pharmacy retailer, we analyze a quasi-field experiment that delegates pricing power to local pharmacy managers. Our analysis reveals that under discretionary pricing, managers incorporate local information into their pricing decisions. However, they are also subject to behavioral biases, which leads to aggressive, sub-optimal price adjustments. We find that managers increase prices of high-priced drugs by 8.6\%, resulting in significant sales and revenue losses. The effect is particularly prominent in stores located in low-competition areas. Moreover, we find that manager experience can alleviate such behavioral biases---more experienced managers from larger stores are not subject to these biases. Our findings highlight the importance of recognizing managers' behavioral biases in business decisions. We provide implications for pricing practices and offer solutions that allow companies to leverage local information while reducing the impact of human biases.

Avian leukemia virus (ALV) is a retrovirus that infects a variety of poultry, and is a vertical transmission of poultry-borne disease. The harm of ALV gradually magnifies with the increase of generations. siRNA with high efficiency, high safety, silence specificity, and unlimited targets have aroused increasing attention from the medical profession, However, there is no suitable vehicle to assist ALV-targeted siRNA for cell internalization. In this paper, ALV-targeted siRNA was first loaded by 13 nm Au NPs layer by layer to synthesize Au@PRP NPs with good stability (78 nm, ζ= +38), which provided an opportunity for the safe diffusion of Au@PRP NPs into cells and specific binding with ALV. Au @PRP NPs could effectively deliver siRNA to DF-1 cells (92.1%) and contain 20 pmol Cy3-siRNA/per million. The strong polyelectrolyte on the surface of Au@PRP NPs can effectively capture cells and co-infect with ALV as high as 88-100%. Moreover, Au@PRP NPs can locate C/E chicken embryo fibroblasts (DF-1 cells) with ALV, and have a significant inhibitory effect on the release of virus particles. Au@PRP NPs will bring new opportunity to research how the multifunctional load design and tracking path of gold nanoparticles influence the uptake/inhibition mechanisms of ALV and the other poultry diseases and guide different target genes to exert their effects.

Exudate regulation, which helps maintain an optimal moisture content in the wound bed and protects the surrounding skin from maceration, is a prerequisite for wound healing. In this study, inspired by the natural hierarchical structure of sugarcane, in which vascular bundles are responsible for transporting water and parenchyma cells are responsible for storing sucrose, we fabricated a continuously self-draining sugarcane stem-based dressing to remove exudates from overhydrated wounds. Sugarcane cellulosic frameworks (SCF), obtained via alkali and de-sugaring treatments of natural sugarcane substrates (SS), were coated with gold nanorods (AuNRs) to facilitate photothermal responsiveness under near-infrared (NIR) irradiation. By mimicking plant transpiration and incorporating a stimulus-responsive feature, natural SS were transformed into exudate-managing dressing materials for accelerated wound healing. As the obtained sugarcane frameworks (Au@SCF) contained abundant vascular bundles and exhibited photothermal responsiveness, it was able to self-drain exudates continuously with a high evaporation efficiency (95%). In order to endow the dressing with antibacterial properties, Ag nanoparticles (AgNPs) was incorporated with Au@SCF to form Ag@Au@SCF. The healing process in a wound model was more rapid with Ag@Au@SCF with NIR irradiation than with a commercial dressing. Moreover, as the parenchyma cells in Ag@Au@SCF formed closed chambers after de-sugaring, Ag@Au@SCF facilitated effective thermal insulation (thermal conductivity of 0.04 W m−1k−1) for protecting the underlying wound, even when the temperature of the top surface was high (53 °C). As this hierarchical structure is naturally existent in other Poaceae plants, which are sustainable green resources, our findings may provide a new strategy for the fabrication of versatile and efficient self-draining dressings for exudate management and wound healing.