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The ambiguous results of multiple CD34 + cell-based therapeutic trials for patients with heart disease have halted the large-scale application of stem/progenitor cell treatment. This study aimed to delineate the biological functions of heterogenous CD34 + cell populations and investigate the net effect of CD34 + cell intervention on cardiac remodeling. We confirmed, by combining single-cell RNA sequencing on human and mouse ischemic hearts and an inducible Cd34 lineage-tracing mouse model, that Cd34 + cells mainly contributed to the commitment of mesenchymal cells, endothelial cells (ECs), and monocytes/macrophages during heart remodeling with distinct pathological functions. The Cd34 + -lineage-activated mesenchymal cells were responsible for cardiac fibrosis, while CD34 + Sca-1 high was an active precursor and intercellular player that facilitated Cd34 + -lineage angiogenic EC-induced postinjury vessel development. We found through bone marrow transplantation that bone marrow-derived CD34 + cells only accounted for inflammatory response. We confirmed using a Cd34-CreER T2 ; R26-DTA mouse model that the depletion of Cd34 + cells could alleviate the severity of ventricular fibrosis after ischemia/reperfusion (I/R) injury with improved cardiac function. This study provided a transcriptional and cellular landscape of CD34 + cells in normal and ischemic hearts and illustrated that the heterogeneous population of Cd34 + cell-derived cells served as crucial contributors to cardiac remodeling and function after the I/R injury, with their capacity to generate diverse cellular lineages., (© 2023. The Author(s).)

Vein graft failure remains a significant clinical problem. Similar to other vascular diseases, stenosis of vein grafts is caused by several cell lines; however, the sources of these cells remain unclear. The objective of this study was to investigate the cellular sources that reshape vein grafts. By analyzing transcriptomics data and constructing inducible lineage-tracing mouse models, we investigated the cellular components of vein grafts and their fates. The sc-RNAseq data suggested that Sca-1+ cells were vital players in vein grafts and might serve as progenitors for multilineage commitment. By generating a vein graft model in which the venae cavae from C57BL/6J wild-type mice were transplanted adjacent to the carotid arteries of Sca-1(Ly6a)-CreERT2; Rosa26-tdTomato mice, we demonstrated that the recipient Sca-1+ cells dominated reendothelialization and the formation of adventitial microvessels, especially at the perianastomotic regions. In turn, using chimeric mouse models, we confirmed that the Sca-1+ cells that participated in reendothelialization and the formation of adventitial microvessels all had a non-bone-marrow origin, whereas bone-marrow-derived Sca-1+ cells differentiated into inflammatory cells in vein grafts. Furthermore, using a parabiosis mouse model, we confirmed that non-bone-marrow-derived circulatory Sca-1+ cells were vital for the formation of adventitial microvessels, whereas Sca-1+ cells derived from local carotid arteries were the source of endothelium restoration. Using another mouse model in which venae cavae from Sca-1 (Ly6a)-CreERT2; Rosa26-tdTomato mice were transplanted adjacent to the carotid arteries of C57BL/6J wild-type mice, we confirmed that the donor Sca-1+ cells were mainly responsible for smooth muscle cells commitment in the neointima, particularly at the middle bodies of vein grafts. In addition, we provided evidence that knockdown/knockout of Pdgfrα in Sca-1+ cells decreased the cell potential to generate SMCs in vitro and decreased number of intimal SMCs in vein grafts. Our findings provided cell atlases of vein grafts, which demonstrated that recipient carotid arteries, donor veins, non-bone-marrow circulation, and the bone marrow provided diverse Sca-1+ cells/progenitors that participated in the reshaping of vein grafts., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Photonic spin skyrmions with deep-subwavelength features have aroused considerable interest in recent years. However, the manipulation of spin structure in the skyrmions in a desired manner is still a challenge, while this is crucial for developing the skyrmion-based applications. Here, an approach of optical spin manipulation by utilizing the spin-momentum equation is proposed to investigate the spin texture in a photonic skyrmion-pair. With the benefit of the proposed approach, a unique spin texture with spin angular momentum varying linearly along the line connecting the two skyrmion centers is theoretically designed and experimentally verified. The optimized spin texture is then applied in a displacement-sensing system, which is capable of attaining pico-metric sensitivity. Compared with the conventional polarization and phase schemes, the spin-based manipulation mechanism provides a new pathway for optical modulation, which is of great value in nanophotonics from both fundamental and application., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: CD34 + cells have been used to treat the patients with heart failure, but the outcome is variable. It is of great significance to scrutinize the fate and the mechanism of CD34 + cell differentiation in vivo during heart failure and explore its intervention strategy., Methods: We performed single-cell RNA sequencing (scRNA-seq) of the total non-cardiomyocytes and enriched Cd34-tdTomato + lineage cells in the murine (male Cd34-CreERT2; Rosa26-tdTomato mice) pressure overload model (transverse aortic constriction, TAC), and total non-cardiomyocytes from human adult hearts. Then, in order to determine the origin of CD34 + cell that plays a role in myocardial fibrosis, bone marrow transplantation model was performed. Furthermore, to further clarify the role of CD34 + cells in myocardial remodeling in response to TAC injury, we generated Cd34-CreERT2; Rosa26-eGFP-DTA (Cre/DTA) mice., Results: By analyzing the transcriptomes of 59,505 single cells from the mouse heart and 22,537 single cells from the human heart, we illustrated the dynamics of cell landscape during the progression of heart hypertrophy, including CD34 + cells, fibroblasts, endothelial and immune cells. By combining genetic lineage tracing and bone marrow transplantation models, we demonstrated that non-bone-marrow-derived CD34 + cells give rise to fibroblasts and endothelial cells, while bone-marrow-derived CD34 + cell turned into immune cells only in response to pressure overload. Interestingly, partial depletion of CD34 + cells alleviated the severity of myocardial fibrosis with a significant improvement of cardiac function in Cd34-CreERT2; Rosa26-eGFP-DTA model. Similar changes of non-cardiomyocyte composition and cellular heterogeneity of heart failure were also observed in human patient with heart failure. Furthermore, immunostaining showed a double labeling of CD34 and fibroblast markers in human heart tissue. Mechanistically, our single-cell pseudotime analysis of scRNA-seq data and in vitro cell culture study revealed that Wnt-β-catenin and TGFβ1/Smad pathways are critical in regulating CD34 + cell differentiation toward fibroblasts., Conclusions: Our study provides a cellular landscape of CD34 + cell-derived cells in the hypertrophy heart of human and animal models, indicating that non-bone-marrow-derived CD34 + cells differentiating into fibroblasts largely account for cardiac fibrosis. These findings may provide novel insights for the pathogenesis of cardiac fibrosis and have further potential therapeutic implications for the heart failure., (© 2023. The Author(s).)

Background: Acute coronary syndrome (ACS) is one of the leading causes of death and is often accompanied by hypertension., Methods: We investigated whether hypertension affects the metabolism of patients with ACS. Serum samples were provided from healthy controls (HCs; n=26), patients with ACS (n=20), or those patients with ACS complicated with hypertension (HTN, n=21), and all were subjected to non-targeted metabolomics analyses based on gas chromatography-mass spectrometry (GC/MS). Differential metabolites were screened using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) provided metabolic pathways related to these metabolites., Results: Compared to those in the HC group, 12 metabolites were significantly upregulated and 6 significantly downregulated in the ACS group; among these, L-cystine and isocitric acid showed the most obvious differences, respectively. Compared to those in the ACS group, 3 metabolites were significantly upregulated and 2 metabolites were significantly downregulated in the ACS-HTN group, among which oleic acid and chenodeoxycholic acid showed the most marked difference, respectively. The five most prominent metabolic pathways involved in differential metabolites between the ACS and HC groups were arginine biosynthesis; oxidative phosphorylation; alanine, aspartate and glutamate metabolism; citrate cycle; and glucagon signaling pathway. The metabolic pathways between the ACS and ACS-HTN groups were steroid biosynthesis, fatty acid biosynthesis, arginine biosynthesis, primary bile acid biosynthesis, and tyrosine metabolism., Conclusions: A comprehensive study of the changes in circulatory metabolomics and the influence of HTN was conducted in patients with ACS. A serum metabolomics test can be used to identify differentially metabolized molecules and allow the classification of patients with ACS or those complicated with HTN., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6409/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Photonic skyrmions and merons are topological quasiparticles characterized by nontrivial electromagnetic textures, which have received increasing research attention recently, providing novel degree of freedom to manipulate light-matter interactions and exhibiting excellent potential in deep-subwavelength imaging and nanometrology. Here, the topological stability of photonic spin meron lattices, which indicates the invariance of skyrmion number and robustness of spin texture under a continuous deformation of the field configuration, is demonstrated by inducing a perturbation to break the C 4 symmetry in the presence spin-orbit coupling in an optical field. We revealed that amplitude perturbation would result in an amplitude-dependent shift of spin center, while phase perturbation leads to the deformation of domain walls, manifesting the metastability of photonic meron. Such spin topology is verified through the interference of plasmonic vortices with a broken rotational symmetry. The results provide new insights on optical topological quasiparticles, which may pave the way towards applications in topological photonics, optical information storage and transfer.

Absent in melanoma 2 (AIM2) is a cytoplasmic sensor that recognises the double-strand DNA. AIM2 inflammasome is a protein platform in the cell that initiates innate immune responses by cleaving pro-caspase-1 and converting IL-1β and IL-18 to their mature forms. Additionally, AIM2 inflammasome promotes pyroptosis by converting Gasdermin-D (GSDMD) to GSDMD-N fragments. An increasing number of studies have indicated the important and decisive roles of the AIM2 inflammasome, IL-1β, and pyroptosis in cardiovascular diseases, such as coronary atherosclerosis, myocardial infarction, ischaemia/reperfusion injury, heart failure, aortic aneurysm and ischaemic stroke. Here, we review the molecular mechanism of the activation and effect of the AIM2 inflammasome in cardiovascular disease, revealing new insights into pathogenic factors that may be targeted to treat cardiovascular disease and related dysfunctions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale: CD34 + cells are believed being progenitors that may be used to treat cardiovascular disease. However, the exact identity and the role of CD34 + cells in physiological and pathological conditions remain unclear., Methods: We performed single-cell RNA sequencing analysis to provide a cell atlas of normal tissue/organ and pathological conditions. Furthermore, a genetic lineage tracing mouse model was used to investigate the role of CD34 + cells in angiogenesis and organ fibrosis., Results: Single-cell RNA sequencing analysis revealed a heterogeneous population of CD34 + cells in both physiological and pathological conditions. Using a genetic lineage tracing mouse model, we showed that CD34 + cells not only acquired endothelial cell fate involved in angiogenesis, but also, CD34 + cells expressing Pi16 may transform into myofibroblast and thus participate in organ fibrosis., Conclusion: A heterogeneous CD34 + cells serve as a contributor not only to endothelial regeneration but also a wound healing response that may provide therapeutic insights into fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Topological spin structures of light, including the Skyrmion, Meron, and bi-Meron, are intriguing optical phenomena that arise from spin-orbit coupling. They have promising potential applications in nano-metrology, data storage, super-resolved imaging and chiral detection. Aside from the electric part of optical spin, of equal importance is the magnetic part, particularly the H-type electromagnetic modes for which the spin topological properties of the field are dominated by the magnetic field. However, their observation and measurement remains absent and faces difficult challenges. Here, we design a unique type of anapole probe to measure specifically the photonic spin structures dominated by magnetic fields. The probe is composed of an Ag-core and Si-shell nanosphere, which manifests as a pure magnetic dipole with no electric response. The effectiveness of the method was validated by characterizing the magnetic field distributions of various focused vector beams. It was subsequently employed to measure the magnetic topological spin structures, including individual Skyrmions and Meron/Skyrmion lattices for the first time. The proposed method may be a powerful tool to characterize the magnetic properties of optical spin and valuable in advancing spin photonics., (© 2022. The Author(s).)

Background: Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored., Methods: C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused ex vivo (Langendorff) or subjected to in vivo left anterior descending coronary artery ligation as models of ischemia/reperfusion injury. Succinate and malonate levels were assessed by liquid chromatography-tandem mass spectrometry LC-MS/MS, in vivo by mass spectrometry imaging, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining., Results: Malonate was robustly protective against cardiac ischemia/reperfusion injury, but only if administered at reperfusion and not when infused before ischemia. The extent of malonate uptake into the heart was proportional to the duration of ischemia. Malonate entry into cardiomyocytes in vivo and in vitro was dramatically increased at the low pH (≈6.5) associated with ischemia. This increased uptake of malonate was blocked by selective inhibition of MCT1 (monocarboxylate transporter 1). Reperfusion of the ischemic heart region with malonate led to selective SDH inhibition in the at-risk region. Acid-formulation greatly enhances the cardioprotective potency of malonate., Conclusions: Cardioprotection by malonate is dependent on its entry into cardiomyocytes. This is facilitated by the local decrease in pH that occurs during ischemia, leading to its selective uptake upon reperfusion into the at-risk tissue, via MCT1. Thus, malonate's preferential uptake in reperfused tissue means it is an at-risk tissue-selective drug that protects against cardiac ischemia/reperfusion injury.

Intrinsic spin-momentum locking is an inherent property of surface electromagnetic fields and its study has led to the discovery of phenomena such as unidirectional guided waves and photonic spin lattices. Previously, dispersion was ignored in spin-momentum locking, resulting in anomalies contradicting the apparent physical reality. Here, we formulate four dispersive spin-momentum equations, revealing in theory that transverse spin is locked with kinetic momentum. Moreover, in dispersive metal or magnetic materials spin-momentum locking obeys the left-hand screw rule. In addition to dispersion, structural features can affect substantially this locking. Remarkably, an extraordinary spin originating from coupling polarization ellipticities is uncovered that depends on the symmetry of the field modes. We further identify the properties of this spin-momentum locking with diverse photonic topological lattices by engineering their rotational symmetry akin to that in solid-state physics. The concept of spin-momentum locking based on photon flow properties translates easily to other classical wave fields.

Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger with immunomodulatory activities in mice, suggesting potential applications as a vaccine immunopotentiator or therapeutic agent. In this study, we evaluated the efficacy of c-di-GMP as an immunopotentiator for pseudorabies virus (PRV) inactivated vaccine in a murine model. We found that c-di-GMP improved the humoral and cellular immune responses induced by PRV inactivated vaccine and its effects on immunity reached the level comparable to that of a live attenuated vaccine. Furthermore, c-di-GMP enhanced the murine antibody response against the viral glycoprotein gB up to 120 days after immunization. The c-di-GMP-adjuvanted PRV inactivated vaccine induced long-term humoral immunity by promoting a potent T follicular helper cell response, which is known to directly control the magnitude of the germinal center B cell response. Furthermore, the c-di-GMP enhanced the response of bone marrow plasma cells and upregulated the expression of Bcl-2 and Mcl-1 , which have been identified as anti-apoptotic regulatory genes of germinal center and memory B cells. Our findings open a new avenue for improving the immune efficacy of PRV inactivated vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hou, Yu, Zhang, Du, Zhang, Cheng, Zheng, Chen and Hou.)

Symmetry and topology govern many electronic, magnetic, and photonic phenomena in condensed matter physics and optics, resulting in counterintuitive skyrmion, meron, and other phenomena important for modern technologies. Here we demonstrate photonic spin lattices as a new topological construct governed by the spin-orbit coupling in an optical field. The symmetry of the electromagnetic field in the presence of the spin-orbit interaction may result in only two types of photonic spin lattices: either hexagonal spin-skyrmion or square spin-meron lattices. We show that these spin structures correspond to the lowest energy of the electromagnetic field configuration, therefore, energetically stable. We further show that in the absence of spin-orbit coupling these spin topologies are degenerated in dynamic field skyrmions, unifying the description of electromagnetic field topologies. The results provide a new understanding of electromagnetic field topology and its transformations as well as new opportunities for applications in quantum technologies, spin optics, and topological photonics.

Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Du, Hou, Yu, Cheng, Chen, Zheng and Hou.)

[Figure: see text].

Spin-momentum locking, a manifestation of topological properties that governs the behavior of surface states, was studied intensively in condensed-matter physics and optics, resulting in the discovery of topological insulators and related effects and their photonic counterparts. In addition to spin, optical waves may have complex structure of vector fields associated with orbital angular momentum or nonuniform intensity variations. Here, we derive a set of spin-momentum equations which describes the relationship between the spin and orbital properties of arbitrary complex electromagnetic guided modes. The predicted photonic spin dynamics is experimentally verified with four kinds of nondiffracting surface structured waves. In contrast to the one-dimensional uniform spin of a guided plane wave, a two-dimensional chiral spin swirl is observed for structured guided modes. The proposed framework opens up opportunities for designing the spin structure and topological properties of electromagnetic waves with practical importance in spin optics, topological photonics, metrology and quantum technologies and may be used to extend the spin-dynamics concepts to fluid, acoustic, and gravitational waves., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Since late 2010, outbreaks of porcine epidemic diarrhea (PED) have been reported in the swine industry in China. A variant PEDV strain that differs from strain CV777 causes prevalent PEDV infections which commercial vaccines based on CV777 cannot provide complete protection. In this study, we designed a new vaccine based on the epidemic PEDV strain AH2012/12, adjuvanted with flagellin, a mucosal adjuvant that induces mucosal and systemic production of IgA. Three groups of pregnant sows were immunized twice, with a 14-day interval, with PEDV adjuvanted with flagellin, PEDV alone, or PBS before farrowing, and newborn piglets from each group were selected and challenged with PEDV. Immunization with this vaccine elicited high levels of IgG, IgA, and neutralizing antibodies in the serum and colostrum of sows, and newborn piglets were protected against PEDV while suckling. This study should guide the prevention and control strategies for PEDV infection, thereby reducing the losses associated with this virus.

Although zinc homeostasis has been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury, the roles of zinc transporters that are critical for zinc homeostasis in I/R injury are poorly understood. The purpose of this study was to test if Zip2, an important zinc importer, plays a role in I/R injury in mouse hearts and explore the mechanism by which Zip2 expression is regulated. Zip2 expression was increased at reperfusion in in vivo mouse hearts, an effect that was abolished by ZnCl 2 , indicating Zip2's attempt to compensate for zinc loss at reperfusion. Further studies showed that upregulation of Zip2 expression was reversed by either pharmacological or genetic inhibition of signal transducers and activators of transcription 3 (STAT3), whereas STAT3 overexpression increased Zip2 expression, indicating that STAT3 accounts for Zip2 upregulation. In support, reperfusion enhanced STAT3 phosphorylation (Tyr 705 ), which was blocked by ZnCl 2 , implying that STAT3 is activated in response to zinc loss. To determine the role of Zip2 in I/R injury, we assessed I/R injury by genetically disrupting Zip2 expression. Knockout of Zip2 genes (Zip2 +/- and Zip2 -/- ) exacerbated I/R injury by increasing infarct size as well as the serum LDH, troponin I (cTnI), and CK-MB activities. In contrast, delivery of Zip2 genes reduced I/R injury. Delivery of STAT3 genes increased STAT3 phosphorylation and reduced I/R injury. However, delivery of the dominant negative STAT3 mutant did not reduce I/R injury. Moreover, delivery of STAT3 genes failed to reduce I/R injury in Zip2 -/- mice. Zip2 upregulated upon reperfusion via STAT3 is cardioprotective and this upregulation may serve as an important intrinsic protective mechanism by which the heart is resistant to I/R injury. The factors involved in the zinc homeostasis (zinc and Zip2) are responsible STAT3 activation and its subsequent cardioprotective action., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Structured illumination microscopy (SIM) is a powerful super-resolved imaging technique which enables to perform fast and in vivo imaging of bio-samples. In order to achieve a better resolution of a SIM system, evanescent waves with larger in-plane wave-vector are preferred for SIM, among which the total internal reflection (TIRF-SIM) and the plasmonic SIM (pSIM) configurations are widely studied. Here, we demonstrated a metal-dielectric waveguide (MDW) based SIM system - termed as MDW-SIM, which can achieve a good compromise between TIRF-SIM and pSIM. The MDW can support a low-loss waveguide mode at an aqueous environment, with an evanescent tail existing above the water/dielectric interface for SIM. A proof-of-concept imaging experiment was performed on fluorescent beads, where a spatial resolution of 86nm was achieved at a 473nm illumination wavelength and a 1.45 numerical aperture objective lens. The proposed MDW-SIM has a great potential for the bio-imaging applications.

Long-lasting humoral immunity is one of the necessary criteria for a successful vaccine. In our previous study, it was demonstrated that the immunopotentiator CVC1302 could improve the humoral immunity induced by the foot and mouth disease virus (FMDV) killed vaccine (KV) with only one dose. Significantly higher FMDV-specific antibody titers and more persistent antibody responses were observed in pigs receiving CVC1302-adjuvanted KV (KV-CVC1302) than in those inoculated with KV alone. In this study, we show that CVC1302 enhances murine IgG responses to FMDV by promoting a potent T follicular helper cell (T FH ) response, which directly controls the magnitude of the germinal center (GC) B cell response. These results indicate a need for studies to assess the capacity of CVC1302 to enhance the efficacy of FMDV KV immunization in pigs, and provide new insights into the development of FMDV vaccines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Porcine epidemic diarrhea (PED) causes 80-100% mortality in neonatal piglets, and its causative agent, the porcine epidemic diarrhea virus (PEDV), poses an important threat to the swine industry worldwide. In this study, we prepared biodegradable poly (d,l-lactide-co-glycolide) (PLGA) nanoparticle-entrapped PEDV killed vaccine antigens (KAg) (PLGA-KAg). Late-term pregnant sows were intranasally inoculated with PLGA-KAg, and the mortality resulting from challenge with highly virulent PEDV was investigated in their passively immunized suckling piglets. PEDV-specific IgG and IgA antibody titers were enhanced in pregnant sows immunized with PLGA-KAg relative to the titers in sows inoculated with KAg. Similar results were seen in the passively immunized suckling piglets of these sows. Improved lymphocyte proliferation responses and IFN-γ levels were induced in pregnant sows immunized with PLGA-KAg compared with those vaccinated with KAg or with Montanide™ ISA 201 VG emulsified killed PEDV vaccine (201-KAg). Importantly, there was less piglet mortality in the group vaccinated with PLGA-KAg than in the groups vaccinated with KAg or 201-KAg. These results demonstrate that PLGA-KAg is a promising candidate vaccine that can provide protective immunity against PEDV infection in suckling piglets., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Porcine reproductive and respiratory syndrome virus (PRRSV) has been causing huge economic losses to the swine industry worldwide. Commercial PRRSV vaccines including killed and modified live ones are available. However the protective efficacy of these vaccines is incomplete. Thus, it is in urgent need to develop safer and more effective PRRSV vaccines. In this study, we constructed a recombinant plasmid co-expressing porcine glutathione peroxidase-1 (GPX1) and the envelope glycoprotein (GP5) encoding-gene of PRRSV (pcDNA3.1-GPX1-LSynORF5), and investigated the immune response induced following inoculation of mice and piglets. Significantly enhanced GP5-specific antibody, PRRSV-specific neutralizing antibody, IFN-γ level, as well as lymphocyte proliferation response, were induced in mice and pigs immunized with the DNA construct encoding GPX1 and GP5 compared with those inoculated with a construct encoding PRRSV GP5 only (pcDNA3.1-SynORF5). The enhanced cellular immune response in pigs induced by pcDNA3.1-GPX1-LSynORF5 was comparable to that induced by the attenuated virus vaccine JXA1-R, although the humoral immune response induced by the plasmid was much lower than the response induced by JXA1-R. Following the challenge with highly pathogenic PRRSV, less-severe clinical signs and rectal temperatures were observed in pigs immunized with the GPX1-GP5 construct compared with the control group. However, the viraemia of groups immunized with plasmid was more severe than that inoculated with JXA1-R, and it is likely that this could be attributed to the poor humoral response induced by the GPX1-GP5 construct. These results demonstrated that inclusion of GPX1 in a PRRSV DNA vaccine leads to an adjuvant effect, enhancing the humoral and cellular responses following vaccination., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease of pigs. Safer and more effective vaccines are urgently needed. In this study, a synthetic ORF5 gene of porcine reproductive and respiratory syndrome virus (PRRSV) was adsorbed onto poly(D, L-lactide-co-glycolide)/polyethylenimine (PLGA/PEI) nanoparticles. We prepared a PLGA-nanoparticle-adsorbed PRRSV DNA vaccine and a PEI-DNA complex. The results showed that these model vaccines could significantly enhance humoral and cellular immune responses when compared with the responses induced by pcDNA3.1-SynORF5, a plasmid construct for expression of PRRSV ORF5. PLGA-branched PEI nanoparticles induced the most efficient immune response. The delivery system and adjuvant provide new models for the development of vaccines against PRRSV.

Porcine respiratory disease complex (PRDC) is of great concern economically, for swine producers worldwide. Co-infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhp) are considered the major causative agents of PRDC, and responsible for mass mortality in pigs. Nevertheless, the molecular mechanisms underlying the host factors involved in pathogenesis and persistent infection have not been clearly established because of a lack of information regarding host responses following co-infection. In the current study, high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages (PAM) to co-infection with highly pathogenic PRRSV (HP-PRRSV) and Mhp. A total of 2152 and 1760 genes were identified as being differentially expressed between the control group and PRRSV+Mhp co-infected group at 6 and 15 h post infection, respectively. The DE genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, defense response, signal transduction. The pathway analysis demonstrated that the most significant pathways were associated with chemokine signaling pathway, cytokine, TLR, RLR and NLR signaling pathways and Jak-STAT signaling pathway. STRING analysis demonstrated that IL-1β is an integral gene in co-infections with PRRSV and Mhp. The present study is the first to document the response of PAMs to co-infection with HP-PRRSV and Mhp. The observed gene expression profile could help with the screening of potential host agents for reducing the prevalence of co-infections, and to further develop our understanding of the molecular pathogenesis associated with PRRSV and Mhp co-infection in pigs., (Copyright © 2014 Elsevier B.V. All rights reserved.)