Co-administration of chicken IL-2 alleviates clinical signs and replication of the ILTV chicken embryo origin vaccine by pre-activating natural killer cells and cytotoxic T lymphocytes.

IMPORTANCE: Chickens immunized with the infectious laryngotracheitis chicken embryo origin (CEO) vaccine (Medivac, PT Medion Farma Jaya) experience adverse reactions, hindering its safety and effective use in poultry flocks. To improve the effect of the vaccine, we sought to find a strategy to alleviate the respiratory reactions associated with the vaccine. Here, we confirmed that co-administering the CEO vaccine with chIL-2 by oral delivery led to significant alleviation of the vaccine reactions in chickens after immunization. Furthermore, we found that the co-administration of chIL-2 with the CEO vaccine reduced the clinical signs of the CEO vaccine while enhancing natural killer cells and cytotoxic T lymphocyte response to decrease viral loads in their tissues, particularly in the trachea and conjunctiva. Importantly, we demonstrated that the chIL-2 treatment can ameliorate the replication of the CEO vaccine without compromising its effectiveness. This study provides new insights into further applications of chIL-2 and a promising strategy for alleviating the adverse reaction of vaccines.

How does the target of green innovation for cleaner production change in management process? Quality targeting and link targeting.

The global economy has accelerated the transition to a green, low-carbon economy. An enterprise's green innovation (GI) is directly related to its capacity for sustainable production as a micro-subject of economic development. This study examined the impact of managerial capacity on enterprise green innovation and changes of green innovation targeting. We used data collected manually from 423 Chinese A-share companies from 2010 to 2017. The effect of various external impact signals was then investigated. This study's findings are as follows: (1) Managerial ability stimulated green enterprise innovation. The marginal effect was 0.0696. While quality targeting has focused more on green invention innovation, managerial capacity significantly improved the marginal impact of green substantial innovation by 0.0375; (2) The clean production link targeting analysis confirmed that enterprises focused on end-of-pipe governance innovation (0.0466), along with new energy innovation (0.0495) rather than energy-saving innovation (-0.0227); (3) The multi-period DDD (Difference in Difference in Difference) model revealed that low-carbon city policy promoted green innovation with a diminishing trend; (4) The voluntary environmental regulation signals, ISO14001 certification, displayed a substitute effect for managerial capacity on enterprise green innovation. This paper provides recommendations, including that enterprises should improve the utilization of new and renewable energy while improving and optimizing production processes. The government should also improve innovation incentive policies and strengthen environmental information disclosure.

The role of digitalization on green economic growth: Does industrial structure optimization and green innovation matter?

The digital economy has demonstrated strong resilience and great potential, under the interwoven influence of the global pandemic and severe environmental concerns across the world. Therefore, there is a need to focus on the value of green economic growth in the digital economy. This paper constructs an evaluation index system and adopts the SEEA (System of Environmental and Economic Accounting) method to measure the digitalization level (Digi) and green economy growth level (GEG) of China. The internal mechanism and linear relationship between digitalization and green economy growth are examined based on the panel data from 2013 to 2019. Moreover, this study explores the spatial spillover effect. The major study findings are as follows: (1) Digitalization and green economy growth represent a steady growth trend, and the former as a whole significantly promotes the latter, with a marginal effect of 1.648. (2) The mechanism analysis indicates the intermediary effects' size of three crucial intermediaries: green technology innovation > advanced industrial structure > the rationalization of industrial structure. (3) Both the "local effect" (0.556; 0.574) and "neighboring effect" (1.382; 1.415) of digitalization on green economy growth are positive under the two weight matrices and display "simultaneous resonance" characteristics based on the spatial perspective. (4) There exists obvious regional spatial heterogeneity and resource endowment heterogeneity. Finally, this study put forward corresponding policy implications, such as construction of new digital infrastructures and guiding green-energy consumption.

A dominant internal gene cassette of high pathogenicity avian influenza H7N9 virus raised since 2018.

The zoonotic H7N9 avian influenza virus emerged with the H9N2-origin internal gene cassette. Previous studies have reported that genetic reassortments with H9N2 were common in the first five human H7N9 epidemic waves. However, our latest work found that the circulating high pathogenicity H7N9 virus has established a dominant internal gene cassette and has decreased the frequency of reassortment with H9N2 since 2018. This dominant cassette of H7N9 was distinct from the cocirculating H9N2, although they shared a common ancestor. As a result, we suppose that this dominant cassette may benefit the viral population fitness and promote its continuous circulation in chickens.

G1-like M and PB2 genes are preferentially incorporated into H7N9 progeny virions during genetic reassortment.

BACKGROUND: Genotype S H9N2 viruses have become predominant in poultry in China since 2010. These viruses frequently donate their whole internal gene segments to other emerging influenza A subtypes such as the novel H7N9, H5N6, and H10N8 viruses. We recently reported that the PB2 and M genes of the genotype S H9N2 virus, which are derived from the G1-like virus, enhance the fitness of H5Nx and H7N9 avian influenza viruses in chickens and mice. However, whether the G1-like PB2 and M genes are preferentially incorporated into progeny virions during virus reassortment remains unclear; whether the G1-like PB2 and M genes from different subtypes are differentially incorporated into new virion progeny remains unknown. RESULTS: We conducted a reassortment experiment with the use of a H7N9 virus as the backbone and found that G1-like M/PB2 genes were preferentially incorporated in progeny virions over F/98-like M/PB2 genes. Importantly, the preference varied among G1-like M/PB2 genes of different subtypes. When competing with F/98-like M/PB2 genes during reassortment, both the M and PB2 genes from the H7N9 virus GD15 showed an advantage, whereas only the PB2 gene from the H9N2 virus CZ73 and the M gene from the H9N2 virus AH320 displayed the advantage. CONCLUSION: Our findings highlight the preferential and variable advantages of H9N2-derived G1-like M and PB2 genes in incorporating them into H7N9 progeny virions over SH14-derived F/98-like M/PB2 genes.

Revisiting cellular immune response to oncogenic Marek's disease virus: the rising of avian T-cell immunity.

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. Although Marek's disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding of molecular and cellular immunity to MDV and its immunopathogenesis has significantly improved, but those findings about cellular immunity to MDV are largely out-of-date, hampering the development of more effective vaccines against MD. T-cell-mediated cellular immunity was thought to be of paramount importance against MDV. However, MDV also infects macrophages, B cells and T cells, leading to immunosuppression and T-cell lymphoma. Additionally, there is limited information about how uninfected immune cells respond to MDV infection or vaccination, specifically, the mechanisms by which T cells are activated and recognize MDV antigens and how the function and properties of activated T cells correlate with immune protection against MDV or MD tumor. The current review revisits the roles of each immune cell subset and its effector mechanisms in the host immune response to MDV infection or vaccination from the point of view of comparative immunology. We particularly emphasize areas of research requiring further investigation and provide useful information for rational design and development of novel MDV vaccines.

The gut microbiota and its metabolites in mice are affected by high heat treatment of Bactrian camel milk.

Heat treatment is the most common method used to make milk safe; however, it leads to changes in the organoleptic and nutritional properties of milk. This study aimed to investigate the effects of different heat treatments on nutrients and microbiota of camel milk. The results showed that the nutrient composition of camel milk could be influenced by heat treatment. Ultra-high-temperature treatment of samples significantly reduced levels of camel milk proteins, vitamin C, and lactose, but did not significantly alter the amino acids content. Analysis of 16S rRNA amplicon sequences demonstrated that the composition of the intestinal microbiota of mice fed different heat-treated camel milks changed, as did the production of short-chain fatty acids as determined by gas chromatography-mass spectrometry. High temperature/short time treatment had similar effects to UHT treatment on microbial diversity of camel milk; however, the low temperature/long time treatment had different effects. In addition, higher-temperature treatments changed the abundance of key bacteria at the genus level. These results demonstrated that different heat treatments not only resulted in some nutrient loss, but also changed the proliferation of some probiotic genera. Our results could provide the basis for the potential industrial application of camel milk processing technologies.

Molecular characterization of bovine leukemia virus reveals existence of genotype 4 in Chinese dairy cattle.

Bovine leukemia virus (BLV) causes enzootic bovine leucosis and is widely spread worldwide, except several European countries, Australia and New Zealand. Although BLV is highly prevalent in China, information about the genetic diversity and evolutionary dynamics of BLV among Chinese dairy herds is still lacking. To determine the genetic variability of BLV, 219 cows from four cities of Ningxia province of China were screened for BLV infection by fluorescence resonance energy transfer (FRET)-PCR and sequencing, 16 selected positive samples were subjected to molecular characterization. Phylogenetic analysis using the neighbor-joining (NJ) method on complete sequences of envelope (env) gene of BLV obtained from China and those available in GenBank (representing BLV genotypes 1-10) revealed that those Chinese strains belonged to genotypes 4 and 6. Totally, 23 mutations were identified and 16 of them were determined to be unique mutations among Chinese strains. Alignment of the deduced amino acid sequences demonstrated six mutations in glycoprotein 51 (gp51) and three mutations in glycoprotein 30 (gp30) located in the identified neutralizing domain (ND), CD8+ T cell epitope, E-epitope, B-epitope, gp51N12 and cytoplasmic domain of transmembrane protein. This study reported for the first time the BLV genotype 4 in China, and further studies are warranted to compare its immunogenicity and pathogenicity with other BLV genotypes.

The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza virus infection.

Polymerase acidic (PA) protein is a multifunctional regulator of influenza A virus (IAV) replication and pathogenesis. In a previous study, we reported that nucleolin (NCL) is a novel PA-interacting host protein. In this study, we further explored the role of NCL during highly pathogenic H5N1 avian influenza virus infection. We found that depletion of endogenous NCL in mammalian cells by siRNA targeting during H5N1 infection resulted in significantly increased viral polymerase activity, elevated viral mRNA, cRNA and vRNA synthesis, accelerated viral replication, and enhanced apoptosis and necrosis. Moreover, siRNA silencing of NCL significantly exacerbated the inflammatory response, resulting in increased secretion of IL-6, TNF-α, TNF-ß, CCL-4, CCL-8, IFN-α, IFN-ß and IFN-γ. Conversely, overexpression of NCL significantly decreased IAV replication. Collectively, these data show that NCL acts as a novel potential antiviral factor during H5N1 infection. Further studies exploring the antiviral mechanisms of NCL may accelerate the development of new anti-influenza drugs.

Centrosymmetric Thiophenemethyleneoxindole-Based Donor-Acceptor Copolymers for Organic Field-Effect Transistors.

Two novel, donor-acceptor-type π-conjugated polymers (P1 and P2) with 3'-(thieno[3,2-b]thiophene-2,5-diylbis(methan-1-yl-1-ylidene))bis-(indolin-2-one) (ITTI) as the acceptor and thiophene/bithiophene as the donor are designed and synthesized by palladium-catalyzed Stille coupling. The optical and electrochemical properties of these polymers are characterized and further implemented into organic field-effect transistors (OFET). Both polymers exhibit excellent thermal stability, broad UV-vis absorption, and high highest occupied molecular orbital energy levels. Thermal annealing induces a well-ordered structure, a highly planar π-system (oxygen-sulfur interaction), and a bathochromic shift in the polymers; furthermore, significant enhancement of the long wavelength intensity is also observed. Both polymers exhibit p-type charge transport behavior, with hole mobilities up to 0.51 cm2 V-1 s-1 for P1 and 0.65 cm2 V-1 s-1 for P2. This work demonstrates that ITTI can be a promising building block for the construction of donor-acceptor polymers with high-performance OFETs.

A randomized controlled study of bedside electrocardiograph-guided tip location technique & the traditional chest radiography tip location technique for peripherally inserted central venous catheter in cancer patients.

Background & objectives: The peripherally inserted central catheter (PICC) has the advantages of higher safety, lower infection rate and longer retention time than peripherally inserted catheter. This study was aimed to evaluate the accuracy and safety of bedside electrocardiograph (ECG)-guided tip location technique in PICC in cancer patients, and compared with traditional chest radiography tip location technique. Methods: Patients were randomly assigned into two groups: The ECG test group patients underwent PICC insertion with ECG-guided tip location, while the control group patients had PICC insertion by the conventional method. The precision of tip location was verified by chest radiography in both groups. The groups were compared with regard to the accuracy of tip placement, anxiety levels before and after the procedure; medical cost and incidence of complications at one week, three months and six months after PICC insertion. Results: Accurate tip location was achieved in 99.30 per cent in the ECG test group vs 92.30 per cent in the control group (P<0.001). At 24 h after the procedure, the anxiety level was significantly lower in the ECG test group. The presence of thrombogenesis was significantly lower in the ECG test group at both three months and six months after the procedure (P=0.04 and P=0.03, respectively). Interpretation & conclusions: The ECG-guided PICC tip location technique was accurate and caused fewer procedure-related complications and less anxiety in patients compared to chest radiography tip location technique. Radiographic confirmation of PICC tip position may not be needed when ECG guidance is used and thus it can help avoid radiation exposure.

Wetting Properties of Defective Graphene Oxide: A Molecular Simulation Study.

In the present work, the wettability of defective graphene oxide (GO) film is studied by molecular dynamics simulations. A water droplet is deposited on the surface of a graphene oxide membrane, and the contact angle is measured by fitting the liquid⁻vapor interface. Although pristine graphene has few hydrophobic properties with a contact angle of 95°, graphene oxide presents more hydrophilic properties, due to the stronger hydrogen bonds interactions at the interface. Moreover, the introduction of vacancy defects at the graphene oxide surface decreases the wettability of graphene oxide. We find that the contact angle of graphene oxide increases from 70° to 82°, with a defective concentration from 0% to 10%. Our results will help provide a new method for controlling the wetting properties of GO and its additional capabilities in device design for applications.

PA-X decreases the pathogenicity of highly pathogenic H5N1 influenza A virus in avian species by inhibiting virus replication and host response.

UNLABELLED: PA-X is a newly discovered protein that decreases the virulence of the 1918 H1N1 virus in a mouse model. However, the role of PA-X in the pathogenesis of highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype in avian species is totally unknown. By generating two PA-X-deficient viruses and evaluating their virulence in different animal models, we show here that PA-X diminishes the virulence of the HPAIV H5N1 strain A/Chicken/Jiangsu/k0402/2010 (CK10) in mice, chickens, and ducks. Expression of PA-X dampens polymerase activity and virus replication both in vitro and in vivo. Using microarray analysis, we found that PA-X blunts the global host response in chicken lungs, markedly downregulating genes associated with the inflammatory and cell death responses. Correspondingly, a decreased cytokine response was recapitulated in multiple organs of chickens and ducks infected with the wild-type virus relative to those infected with the PA-X-deficient virus. In addition, the PA-X protein exhibits antiapoptotic activity in chicken and duck embryo fibroblasts. Thus, our results demonstrated that PA-X acts as a negative virulence regulator and decreases virulence by inhibiting viral replication and the host innate immune response. Therefore, we here define the role of PA-X in the pathogenicity of H5N1 HPAIV, furthering our understanding of the intricate pathogenesis of influenza A virus. IMPORTANCE: Influenza A virus (IAV) continues to pose a huge threat to global public health. Eight gene segments of the IAV genome encode as many as 17 proteins, including 8 main viral proteins and 9 accessory proteins. The presence of these accessory proteins may further complicate the pathogenesis of IAV. PA-X is a newly identified protein in segment 3 that acts to decrease the virulence of the 1918 H1N1 virus in mice by modulating host gene expression. Our study extends these functions of PA-X to H5N1 HPAIV. We demonstrated that loss of PA-X expression increases the virulence and replication of an H5N1 virus in mice and avian species and alters the host innate immune and cell death responses. Our report is the first to delineate the role of the novel PA-X protein in the pathogenesis of H5N1 viruses in avian species and promotes our understanding of H5N1 HPAIV.

Virulence determinants in the PB2 gene of a mouse-adapted H9N2 virus.

The molecular bases of adaptation and pathogenicity of H9N2 influenza virus in mammals are largely unknown. Here, we show that a mouse-adapted PB2 gene with a phenylalanine-to-leucine mutation (F404L) mainly contributes to enhanced polymerase activity, replication, and pathogenicity of H9N2 in mice and also increases the virulence of the H5N1 and 2009 pandemic H1N1 influenza viruses. Therefore, we defined a novel pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.

Identification of intraocular inflammatory mediators in patients with endophthalmitis.

PURPOSE: Endophthalmitis is mediated by inflammatory cytokines. We employed a quantitative antibody array, which profiles protein expression and function in a high-throughput manner, to identify inflammatory mediators in the infectious aqueous and vitreous humor from patients with endophthalmitis. METHODS: In this prospective study, aqueous humor (AH) and vitreous humor (VH) samples were obtained from 30 patients with endophthalmitis and were collected during anterior chamber paracentesis and vitrectomy. Control samples were obtained from 32 healthy donors. We examined the expression of 20 inflammatory mediators in AH and VH using a quantitative antibody protein array. Hierarchical cluster analysis based on the expression of the quantified cytokines was applied to identify the specificity of endophthalmitis disease. Validation analysis using enzyme-linked immunosorbent assay (ELISA) was performed to confirm the expression of the cytokines identified in the AH and VH samples. RESULTS: Our results demonstrated elevated expression of interleukin (IL)-1ß, IL-6, and macrophage inflammatory protein (MIP)-3α in AH or VH from patients with endophthalmitis. The concentration of IL-17 was upregulated in AH from the patients. The expression of IL-2, IL-5, IL-21, and transforming growth factor (TGF)-ß1 was downregulated in AH from the patients. The cluster analysis demonstrated that the cytokine profile expression in AH or VH significantly differed between the patients with endophthalmitis and the healthy controls. Confirmation with ELISA validated the increase in IL-1ß, IL-6, and MIP-3α in the AH and VH samples from the patients with endophthalmitis. CONCLUSIONS: Increased expression of IL-1ß, IL-6, IL-17, and MIP-3α and decreased expression of IL-2, IL-5, IL-21, and TGF-ß in the AH and VH suggests an abnormal cytokine profile in patients with endophthalmitis. Knowledge of this will aid in the diagnosis of infectious endophthalmitis.

Multifunctional Poly(methyl vinyl ether-co-maleic anhydride)-graft-hydroxypropyl-ß-cyclodextrin Amphiphilic Copolymer as an Oral High-Performance Delivery Carrier of Tacrolimus.

In order to improve oral bioavailability of tacrolimus (FK506), a novel poly(methyl vinyl ether-co-maleic anhydride)-graft-hydroxypropyl-ß-cyclodextrin amphiphilic copolymer (CD-PVM/MA) is developed, combining the bioadhesiveness of PVM/MA, P-glycoprotein (P-gp), and cytochrome P450-inhibitory effect of CD into one. The FK506-loaded nanoparticles (CD-PVM/MA-NPs) were obtained by solvent evaporation method. The physiochemical properties and intestinal absorption mechanism of FK506-loaded CD-PVM/MA-NPs were characterized, and the pharmacokinetic behavior was investigated in rats. FK506-loaded CD-PVM/MA-NPs exhibited nanometer-sized particles of 273.7 nm, with encapsulation efficiency as high as 73.3%. FK506-loaded CD-PVM/MA-NPs maintained structural stability in the simulated gastric fluid, and about 80% FK506 was released within 24 h in the simulated intestinal fluid. The permeability of FK506 was improved dramatically by CD-PVM/MA-NPs compared to its solution, probably due to the synergistic inhibition effect of P-gp and cytochrome P450 3A (CYP3A). The intestinal biodistribution of fluorescence-labeled CD-PVM/MA-NPs confirmed its good bioadhesion to the rat intestinal wall. Two endocytosis pathways, clathrin- and caveolae-mediated endocytosis, were involved in the cellular uptake of CD-PVM/MA-NPs. The important role of lymphatic transport in nanoparticles' access to the systemic circulation, about half of the contribution to oral bioavailability, was observed in mesenteric lymph duct ligated rats. The AUC0-24 of FK506 loaded in nanoparticles was enhanced up to 20-fold compared to FK506 solutions after oral administration. The present study suggested that the novel multifunctional CD-PVM/MA is a promising efficient oral delivery carrier for FK506, due to its ability in solubilization, inhibitory effects on both P-gp and CYP 3A, high bioadhesion, and sustained release capability.

Novel H5 clade 2.3.4.6 viruses with both α-2,3 and α-2,6 receptor binding properties may pose a pandemic threat.

The emerging H5 clade 2.3.4.6 viruses of different NA subtypes have been detected in different domestic poultry in China. We evaluated the receptor binding property and transmissibility of four novel H5 clade 2.3.4.6 subtype highly pathogenic avian influenza viruses. The results show that these viruses bound to both avian-type (α-2,3) and human-type (α-2,6) receptors. Furthermore, we found that one of these viruses, GS/EC/1112/11, not only replicated but also transmitted efficiently in guinea pigs. Therefore, such novel H5 subtype viruses have the potential of a pandemic threat.

Tertiary montane origin of the Central Asian flora, evidence inferred from cpDNA sequences of Atraphaxis (Polygonaceae).

Atraphaxis has approximately 25 species and a distribution center in Central Asia. It has been previously used to hypothesize an origin from montane forest. We sampled 18 species covering three sections within the genus and sequenced five cpDNA spacers, atpB-rbcL, psbK-psbI, psbA-trnH, rbcL, and trnL-trnF. BEAST was used to reconstruct phylogenetic relationship and time divergences, and S-DIVA and Lagrange were used, based on distribution area and ecotype data, for reconstruction of ancestral areas and events. Our results appear compatible with designation of three taxonomic sections within the genus. The generic stem and crown ages were Eocene, approximately 47 Ma, and Oligocene 27 Ma, respectively. The origin of Atraphaxis is confirmed as montane, with an ancestral area consisting of the Junggar Basin and uplands of the Pamir-Tianshan-Alatau-Altai mountain chains, and ancestral ecotype of montane forest. Two remarkable paleogeographic events, shrinkage of the inland Paratethys Sea at the boundary of the late Oligocene and early Miocene, and the time intervals of cooling and drying of global climate from 24 (22) Ma onward likely facilitated early diversification of Atraphaxis, while rapid uplift of the Tianshan Mountains during the late Miocene may have promoted later diversification.

YOLO-SK: A lightweight multiscale object detection algorithm.

YOLOv5 is an excellent object-detection model. However, it fails to fully use multiscale information when detecting objects with significant scale variations. It might use irrelevant contextual information, leading to incorrect predictions, particularly for low-performance devices. In this study, we selected lightweight YOLOv5s as the baseline model and proposed an improved model called YOLO-SK to overcome this limitation. YOLO-SK introduced several key improvements, the most important being the collaborative work of the weighted dense feature fusion network and SK attention prediction head. The proposed weighted dense feature fusion network could dynamically fuse features at different scales using autonomous learning parameters and cross-layer fusion capabilities. This enabled a balanced feature fusion ability in the output feature maps of different scales, thereby enhancing the richness of the effective information in the fused feature maps. The prediction head equipped with the SK attention mechanism broadened the scope of the model's receptive field and sharpened the focus on the target characteristics. This made it possible to glean more information about the target from the feature map output by employing a weighted dense feature fusion network. In addition, in order to improve the model's performance in terms of both accuracy and volume, we implemented the SIoU loss function and the Ghost Conv. The use of the model allowed for a more precise and in-depth comprehension of the event, which was made possible by all of these various methods of improvement. Extensive testing done on the PASCAL VOC 2007 and 2012 datasets showed that YOLO-SK was able to achieve considerable gains in prediction accuracy when compared with the baseline model (YOLOv5s), all while keeping the same level of model complexity. To be more specific, mAP@.5 increased by 2.6 %, and mAP@.5:.95 increased by 4.8 %. The advancements that were made and detailed in this paper could serve as a springboard for additional research that aims to improve the precision of multiscale object identification models for low-performance devices.