Correction: Temperature-sensitive foaming agent developed for smart foam drainage technology.

[This corrects the article DOI: 10.1039/D2RA04034D.].

Adaptor complex-mediated trafficking of Newcastle disease virus fusion protein is regulated by the YLMY motif of its cytoplasmic tail.

Previously, we reported that the mediation of Newcastle disease virus (NDV) pathogenicity by the 524YLMY527 motif depends mainly on the regulation of F protein transport to the cell surface. The virus and host determinants that govern this intracellular trafficking remain unknown. Here, we confirmed that host adaptor protein (AP) complexes are involved in NDV infection using small interfering RNA. The transport of viral F protein to the cell surface depends on host transport proteins. We observed that the trends for host expression of AP complexes AP1M1 and AP2M1 were similar to those of mutated F proteins, especially in the membrane protein. NDV F protein interacted with AP1M1 and AP2M1, and the YLMY motif influenced this interaction. Knockdown of AP1M1 or AP2M1 suppressed the intracellular and extracellular virus titre of mutated-YLMY-motif NDVs, especially rSG10*-F/Y527A and rSG10*-F/Y524AY527A, to varying degrees. Therefore, the YLMY motif regulates AP-mediated viral F protein transportation from the cytoplasm to the cell surface and subsequently affects viral titer. We further found that the YLMY-motif mutants were differently associated with the process of AAK1 and GAK kinase-mediated AP - viral F protein interaction. These data demonstrate that the essential YLMY motif located in the NDV F protein cytoplasmic tail recruits AP to direct the F protein to the cell surface, which is necessary for its ability to affect virus budding. This study provides support for a deeper understanding of virus and host determinants that facilitate virus trafficking, which can be exploited in the design of novel antiviral therapies.

In Vivo Analysis of the Dynamic Motion Stability Characteristics of Geese's Neck.

The goose's neck is an excellent stabilizing organ with its graceful neck curves and flexible movements. However, the stabilizing mechanism of the goose's neck remains unclear. This study adopts a dynamic in vivo experimental method to obtain continuous and accurate stable motion characteristics of the goose's cervical vertebra. Firstly, the results showed that when the body of a goose was separately moved back and forth along the Y direction (front and back) and Z direction (up and down), the goose's neck can significantly stabilize the head. Then, because of the limitation of the X-ray imaging area, the three-dimensional intervertebral rotational displacements for vertebrae C4-C8 were obtained, and the role that these five segments play in the stabilization of the bird's neck was analyzed. This study reveals that the largest range of the adjacent vertebral rotational movement is around the X-axis, the second is around the Y-axis, and the smallest is around the Z-axis. This kinematic feature is accord with the kinematic feature of the saddle joint, which allows the flexion/around X-axis and lateral bending/around Y-axis, and prevents axial rotation/around Z-axis.

Temperature-sensitive foaming agent developed for smart foam drainage technology.

The conventional foam drainage technology needs to be defoamed, which is not convenient for its popularization and application. In view of this problem, from the point of molecular design, a temperature-responsive surfactant was designed and synthesized. In the synthetic process, polyoxyethylene alkyl ether carboxylic acid, diethanolamine and sodium chloroacetate were used as raw materials. First, polyoxyethylene alkyl ether carboxylic acid reacted with diethanolamine to generate a tertiary amine with hydroxyl catalyzed by sulfoxide chloride, and the intermediate product then reacted with sodium chloroacetate by the quaternary amine reaction to afford the target temperature-responsive surfactant. The foaming agent can achieve conformational transformation in the temperature range of 20 °C to 120 °C, resulting in the structural change of the self-assembly and regulating the stability of the foam, which makes the formed foam burst rapidly at low temperatures and be super-stable at high temperatures. The indoor evaluations show that the foaming height of the foaming agent is basically unchanged at the same temperature after 4 temperature-changing cycles, and the temperature-controlled defoaming rate reaches 90%, indicating that it has the intelligent temperature response switching performance of "high-temperature defoaming, low-temperature defoaming". Its preparation process is simple, low-cost, and environmentally friendly. It is expected to be popularized and applied in the field of gas fields, expand the application scope of foam drainage technology, reduce the cost of foam drainage, and help the efficient development of gas fields.

Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Chinese interpreting students' learning motivation and performance in the Covid-19 context: a quasi-experimental study.

Covid-19 has brought about profound changes and challenges to the interpreting profession, and this study aims to explore Chinese students' learning motivation and performance in the new context. Motivation is a main determinant of performance. Referring to the studies on intrinsic motivation, ideal self, and Maslow's needs theory as well as the characteristics of interpreting, we have summarized six motivation dimensions, including safety, social, esteem, cognitive, actualization, and transcendence ones. A questionnaire was designed to address the six motivation dimensions. Experimental teaching was carried out on two undergraduate classes. The Covid-19 context was incorporated into the experimental group but not the control group. Three parallel tests were organized, and students completed the motivation questionnaire after each test. Data analyses showed that the experimental group's actualization and transcendence motivation dimensions increased significantly after the experimental teaching, but not the control group, and the experimental group also had a significantly higher score in the final test. It implied that the actualization and transcendence dimensions were closely related to students' performance.

Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy.

Alzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to the hindrance of the blood-brain barrier (BBB) and the complex pathological condition of AD.  Therefore, a multifunctional nanocarrier (Rapa@DAK/siRNA) for AD treatment is constructed to achieve small interfering RNA of ß-site precursor protein (APP) cleaving enzyme-1 (BACE1 siRNA) and rapamycin co-delivery into the brain, based on Aleuria aurantia lectin (AAL) and ß-amyploid (Aß)-binding peptides (KLVFF) modified PEGylated dendrigraft poly-l-lysines (DGLs) via intranasal administration. Nasal administration provides an effective way to deliver drugs directly into the brain through the nose-to-brain pathway. AAL, specifically binding to L-fucose located in the olfactory epithelium, endows Rapa@DAK/siRNA with high brain entry efficiency through intranasal administration. KLVFF peptide as an Aß targeting ligand and aggregation inhibitor enables nanoparticles to bind with Aß, inhibit Aß aggregation, and reduce toxicity. Meanwhile, the release of BACE1 siRNA and rapamycin is confirmed to reduce BACE1 expression, promote autophagy, and reduce Aß deposition. Rapa@DAK/siRNA is verified to improve the cognition of transgenic AD mice after intranasal administration. Collectively, the multifunctional nanocarrier provides an effective and potential intranasal avenue for combination therapy of AD.

Glymphatic System and Subsidiary Pathways Drive Nanoparticles Away from the Brain.

Although drug delivery systems (DDS) are efficient in brain delivery, they face failure in clinical settings due to their potential toxicity to the central nervous system. Little is known about where the DDS will go after brain delivery, and no specific elimination route that shares a passage with DDS has been verified. Hence, identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation. In this study, we investigated nonreactive gold nanoclusters, which can deliver into the brain, to determine the elimination route of DDS. Subsequently, nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations (77.8 ± 23.2% and 43.7 ± 23.4% contribution). Furthermore, the nanoclusters could be actively transported across the blood-brain barrier (BBB) by exosomes (30.5 ± 27.3% and 29.2 ± 7.1% contribution). In addition, microglia promoted glymphatic drainage and passage across the BBB. The simultaneous work of the glymphatic system, BBB, and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further brain-delivery DDS.

Construction and immune efficacy of a recombinant turkey herpesvirus vaccine strain expressing fusion protein of genotype VII Newcastle disease virus.

Herpesvirus of turkeys (HVT), a commonly used live vaccine against Marek's disease, has proven to be a highly effective viral vector for the generation of recombinant vaccines that deliver protective antigens of other avian pathogens. In this study, a vaccine designated rHVT-NDV-opti F was constructed by inserting a codon-optimized genotype Ⅶ Newcastle disease virus (NDV) fusion (F) gene into the US2 gene of HVT Fc126 vaccine strain using CRISPR/Cas9 gene-editing technology coupled with two single-guide RNAs (sgRNA). The F protein expression of rHVT-NDV-opti F was detectable by western blotting and an indirect immunofluorescence assay. Compared with wildtype HVT, rHVT-NDV-opti F has similar plaque morphology but lower in vitro replication capacity. The F protein of rHVT-NDV-opti F is genetically stable and predominantly expressed in the cell plasma. Immunization of one-day-old specific pathogen-free chickens with 4000 plaque-forming units of rHVT-NDV-opti F induced NDV-specific antibodies and provided 70% protection against a homologous NDV challenge, effectively reducing virus shedding, clinical signs, tissue viral load, and mortality. These results suggest that rHVT-NDV-opti F could be a potential vaccine candidate against Newcastle disease in chickens and that HDR-CRISPR/Cas9 combined with dual sgRNA can rapidly and efficiently construct HVT-vectored vaccine candidates.

Turbulent Drag Reduction with an Ultra-High-Molecular-Weight Water-Soluble Polymer in Slick-Water Hydrofracking.

Water-soluble polymers as drag reducers have been widely utilized in slick-water for fracturing shale oil and gas reservoirs. However, the low viscosity characteristics, high operating costs, and freshwater consumption of conventional friction reducers limit their practical use in deeper oil and gas reservoirs. Therefore, a high viscosity water-soluble friction reducer (HVFR), poly-(acrylamide-co-acrylic acid-co-2-acrylamido-2-methylpropanesulphonic acid), was synthesized via free radical polymerization in aqueous solution. The molecular weight, solubility, rheological behavior, and drag reduction performance of HVFR were thoroughly investigated. The results showed that the viscosity-average molecular weight of HVFR is 23.2 × 106 g⋅mol-1. The HVFR powder could be quickly dissolved in water within 240 s under 700 rpm. The storage modulus (G') and loss modulus (G″) as well as viscosity of the solutions increased with an increase in polymer concentration. At a concentration of 1700 mg⋅L-1, HVFR solution shows 67% viscosity retention rate after heating from 30 to 90 °C, and the viscosity retention rate of HVFR solution when increasing CNaCl to 21,000 mg⋅L-1 is 66%. HVFR exhibits significant drag reduction performance for both low viscosity and high viscosity. A maximum drag reduction of 80.2% is attained from HVFR at 400 mg⋅L-1 with 5.0 mPa⋅s, and drag reduction of HVFR is 75.1% at 1700 mg⋅L-1 with 30.2 mPa⋅s. These findings not only indicate the prospective use of HVFR in slick-water hydrofracking, but also shed light on the design of novel friction reducers utilized in the oil and gas industry.

Replicase 1a gene plays a critical role in pathogenesis of avian coronavirus infectious bronchitis virus.

Avian coronavirus infectious bronchitis virus (IBV) is an important pathogen threatening poultry production worldwide. Here, two recombinant IBVs (rYN-1a-aYN and rYN-1b-aYN) were generated in which ORF1a or ORF1b of the virulent YN genome were replaced by the corresponding regions from the attenuated strain aYN. The pathogenicity and virulence of rIBVs were evaluated in ovo and in vivo. The results revealed that mutations in the ORF1a gene during passage in embryonated eggs caused the decreased pathogenicity of virulent IBV YN strain, proven by determination of virus replication in ECEs and CEK cells, the observation of clinical signs, gross lesions, microscopic lesions, tracheal ciliary activity and virus distribution in chickens following exposure to rIBVs. However, mutations in ORF1b had no obvious effect on virus replication in both ECEs and CEK cells, or pathogenicity in chickens. Our findings demonstrate that the replicase 1a gene of avian coronavirus IBV is a determinant of pathogenicity.

Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer.

The current nanomedicines for cancer therapy based on the enhance permeability and retention (EPR) effect remain insufficient to satisfy the clinical need, and the challenges hindering nanomedicines delivery should be conquered for strong therapeutic efficacy. To address these problems, a membrane-coated laser-responsive shape changeable nanomedicine, I-P@NPs@M, is reported. The covering macrophage membrane promotes the circulation and tumor targeting of nanomedicines. Then the chlorin e6 (Ce6) in I-P@NPs@M can convert 650 nm laser into reactive oxygen species (ROS) to trigger the spherical micelles changing into nanofibers for strong retention in tumor region, consequently the linear nanofibers long locate and sustainably release drugs. On the other hand, the ROS not only directly kills tumor cells by photodynamic therapy but stimulates the dimeric paclitaxel (PTX) generating monomeric PTX. The combinational chemo- photodynamic therapy heavily suppresses tumor growth and inducing immunogenic cell death, which is synergistic with Indoximod (IND) inhibiting the IDO pathway to activate immune response for immunotherapy. By chemotherapy, photodynamic therapy and immunotherapy gathering, the treatment of I-P@NPs@M + laser shows the best antitumor effect, resulting in 85.27 ± 12.80% suppression of breast cancer in mice model, and also remarkably inhibits lung metastasis.

The S2 Subunit of QX-type Infectious Bronchitis Coronavirus Spike Protein Is an Essential Determinant of Neurotropism.

Some coronaviruses (CoVs) have an extra furin cleavage site (RRKR/S, furin-S2' site) upstream of the fusion peptide in the spike protein, which plays roles in virion adsorption and fusion. Mutation of the S2' site of QX genotype (QX-type) infectious bronchitis virus (IBV) spike protein (S) in a recombinant virus background results in higher pathogenicity, pronounced neural symptoms and neurotropism when compared with conditions in wild-type IBV (WT-IBV) infected chickens. In this study, we present evidence suggesting that recombinant IBV with a mutant S2' site (furin-S2' site) leads to higher mortality. Infection with mutant IBV induces severe encephalitis and breaks the blood-brain barrier. The results of a neutralization test and immunoprotection experiment show that an original serum and vaccine can still provide effective protection in vivo and in vitro. This is the first demonstration of IBV-induced neural symptoms in chickens with encephalitis and the furin-S2' site as a determinant of neurotropism.

NP protein and F protein of pigeon paramyxovirus type 1 are associated with its low pathogenicity in chickens.

In this study, we investigated which structural proteins of pigeon paramyxovirus type 1 (PPMV-1) are responsible for its low pathogenicity in chickens. The results revealed that the pathogenicity of the virus is determined by multiple genes. The NP protein and F protein were found to have the strongest individual effect on virulence, and this effect further enhanced when the two proteins were expressed in combination. Our study highlights the influence of the NP and F proteins on the pathogenicity of PPMV-1 in chickens.

Molecular characteristics and pathogenicity analysis of QX-like avian infectious bronchitis virus isolated in China in 2017 and 2018.

Proportions of QX-like genotype infectious bronchitis virus (IBV) isolates have increased over time. Here, to better understand the epidemiology and pathogenicity of IBV in China and control the spread of infectious bronchitis (IB), we conducted sequence analyses and examined the pathogenicity of 5 field isolates from diseased flocks in 2017 and 2018. Sequence analyses revealed that all the 5 strains, as well as many recent field isolates from other researchers, belonged to the QX-like IBV genotype, which were distantly related to commercial vaccine strains. Viral pathogenicity experiments showed that the isolates caused high morbidity and severe ciliostasis in chickens, although they caused milder lethality. This provides further evidence that QX-like IBV emergence remains a major problem in the poultry industry, and information on IBV epidemiology and pathogenicity may help to control IB.

S gene and 5a accessory gene are responsible for the attenuation of virulent infectious bronchitis coronavirus.

To explore the critical genes associated with infectious bronchitis virus (IBV) virulence, we compared the genome sequences of virulent YN strain and its attenuated strain aYN. Accumulation of mutations in the S gene and the accessory gene 5a were observed, suggesting a potential role in the loss of viral pathogenicity. Two recombinant IBVs (rIBVs) with replacement of the S gene or 5a with corresponding regions from aYN were rescued to verify this speculation. Embryo mortality time/rate showed that rYN-S-aYN and rYN-5a-aYN had an attenuated phenotype in ovo. Replication assay in ovo and in vitro demonstrated the rIBVs had similar replication patterns with wild-type rIBV. Both rIBVs showed reduced mortality, tissue lesions and tissue virus titers in chicken. In conclusion, S gene and 5a accessory gene are responsible for the attenuation of virulent IBV. Insight into the genes responsible for virus attenuation will facilitate the development of future vaccines against IBV.

Pathogenicity differences between a newly emerged TW-like strain and a prevalent QX-like strain of infectious bronchitis virus.

TW-like IBV isolates have appeared frequently in recent years in mainland China. In this study, we compared the TW-like IBV GD strain and the predominant QX-like SD strain in terms of serology and pathogenicity to 3-week-old specific-pathogen-free chickens. Both strains could cause severe respiratory distress and renal lesions, with a mortality rate were approximately 20%. Virus were continuously shed via the respiratory tract and cloaca. However, the infection pattern of the two isolates were different. The GD strain persisted for a longer duration and caused extensive damages to the tracheas and lungs. Moreover, chickens infected with the GD strain showed inefficient recovery of damaged cilia after infection. Our findings suggested that the newly emerged TW-like IBV GD strain showed obvious differences in pathogenicity, tissue tropism and replication efficiency compared with the QX-like IBV SD strain, with the TW-like GD strain showing stronger tropism to the respiratory tract and a longer duration of clinical signs.

Photothermal therapy of cancer cells using novel hollow gold nanoflowers.

This article presents a new strategy for fabricating large gold nanoflowers (AuNFs) that exhibit high biological safety under visible light and very strong photothermal cytotoxicity to HeLa cells under irradiation with near-infrared (NIR) light. This particular type of AuNF was constructed using vesicles produced from a multiamine head surfactant as a template followed by depositing gold nanoparticles (AuNPs) and growing their crystallites on the surface of vesicles. The localized surface plasmon-resonance spectrum of this type of AuNF can be easily modulated to the NIR region by controlling the size of the AuNFs. When the size of the AuNFs increased, biosafety under visible light improved and cytotoxicity increased under NIR irradiation. Experiments in vitro with HeLa cells and in vivo with small mice have been carried out, with promising results. The mechanism for this phenomenon is based on the hypothesis that it is difficult for larger AuNFs to enter the cell without NIR irradiation, but they enter the cell easily at the higher temperatures caused by NIR irradiation. We believe that these effects will exist in other types of noble metallic NPs and cancer cells. In addition, the affinity between AuNPs and functional biomolecules, such as aptamers and biomarkers, will make this type of AuNF a good recognition device in cancer diagnosis and therapy.

Synthesis of highly branched gold nanodendrites with a narrow size distribution and tunable NIR and SERS using a multiamine surfactant.

Gold nanodendrites with a long and densely branched morphology were fabricated by a seed-mediated method in a solution containing gold nanoparticles (AuNPs), bis(amidoethyl-carbamoylethyl)octadecylamine (C18N3), HAuCl4, and the reducing agent ascorbic acid (AA). The length and density of the branches could be mediated by changing the AuNP seed and AA concentrations. The amphiphilic C18N3 molecules function as a template and induce the unique morphology of the AuNPs/C18N3 structures. The localized surface plasmon resonance (LSPR) peaks of the gold nanodendrites can be modulated from the visible (∼530 nm) to the near-infrared region (∼1100 nm) of the electromagnetic spectrum. Surface-enhanced Raman scattering (SERS) signals using rhodamine can also be mediated by changing the seed and AA concentrations. These unique highly branched gold nanodendrites with a narrow size distribution and tunable NIR and SERS spectra should have great potential in sensing applications.

Shape homogenization and long-range arrangement of gold nanorods using a pH-responsive multiamine surfactant.

A relatively new and efficient method is reported here for the purification and arrangement of high-aspect-ratio gold nanorods (AuNRs) using a multiamine surfactant, bis[[(amidoethyl)carbamoyl]ethyl]octadecylamine (C18N3), which strongly adsorbs to the surface of AuNRs. The adsorbed layers of the multiamine surfactant on AuNRs exhibit the ability to deaggregate gold nanoparticles at low pH in an aqueous medium and to promote their aggregation at high pH. Through regulation of the pH of the dispersion medium, a well-ordered arrangement of 99% monodisperse AuNRs was obtained, having dimensions of approximately 18 nm diameter and 353 nm length and an area of several dozens of square micrometers, which is much larger than what has been reported in the literature. A very strong optical absorption in the near-infrared region of as-prepared AuNRs was shown. This strategy of using pH-responsive multiamine surfactant to mediate both the homogenization in shape and the arrangement of nanoparticles provides a new methodology for the formation of nanoparticle assemblies.