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Early myocardial ischemia-induced sudden cardiac deaths (EMI-SCD) remain a great diagnostic challenge for forensic pathologists due to no gross or non-specific histological pathology. The goal of this study was to assess whether three secretory proteins, related with cellular endoplasmic reticulum stress, can be applied in forensic diagnosis of EMI-SCD. These markers included LMAN2, CAPN-1, and VCP and were compared with two clinically used markers (CK-MB and cTnI). A total of 21 EMI-SCD cases with a mean age of 53.0 (± 10.5) years and a mean ischemia interval of

Coronary artery spasm (CAS) plays an important role in the pathogenesis of many ischemic heart entities; however, there are no established diagnostic biomarkers for CAS in clinical and forensic settings. This present study aimed to identify such serum biomarkers by establishing a rabbit CAS provocation model and integrating quantitative serum proteomics, parallel reaction monitoring/mass spectrometry-based targeted proteomics, and partial least-squares discriminant analysis (PLS-DA). Our results suggested that SELENBP1 and VCL were potential candidate biomarkers for CAS. In independent clinical samples, SELENBP1 and VCL were validated to be significantly lower in serum but not blood cells from CAS patients, with the reasons for this possibly due to the decreased secretion from cardiomyocytes. The areas under the curve of the receiver operating characteristics (ROC) analysis were 0.9384 for SELENBP1 and 0.9180 for VCL when diagnosing CAS. The CAS risk decreased by 32.3% and 53.6% for every 10 unit increases in the serum SELENBP1 and VCL, respectively. In forensic samples, serum SELENBP1 alone diagnosed CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, and its combination with VCL yielded a diagnostic specificity of 100.0%, which was superior to the traditional biomarkers of cTnI and CK-MB. Therefore, serum SELENBP1 and VCL could be effective biomarkers for both the clinical and forensic diagnosis of CAS.

In transition-metal dipnictides $TmPn_2$ ($Tm$ = Ta, Nb; $Pn$ = P, As, Sb), the origin of extremely large magnetoresistance (XMR) is yet to be studied by the direct visualization of the experimental band structures. Here, using angle-resolved photoemission spectroscopy, we map out the three-dimensional electronic structure of NbAs$_2$. The open-orbit topology contributes to a non-negligible part of the Fermi surfaces (FSs), like that of the isostructural compound MoAs$_2$, where the open FS is proposed to likely explain the origin of XMR. We further demonstrate the observation of open characters in the overall FSs of W$_2$As$_3$, which is also a XMR semimetal with the same space group of $C$12/$m$1 as $TmPn_2$ family and MoAs$_2$. Our results suggest that the open-orbit FS topology may be a shared feature between XMR materials with the space group of $C$12/$m$1, and thus could possibly play a role in determining the corresponding XMR effect together with the electron-hole compensation., 7 pages, 4 figures, Editor's pick

We derived explicit expressions of symmetry operators on Wannier basis, and implemented these operators in WannSymm software. Based on this implementation, WannSymm can i) symmetrize the real-space Hamiltonian output from Wannier90 code, ii) generate symmetry operators of the little group at a specific k-point, and iii) perform symmetry analysis for Wannier band structure. In general, symmetrized Hamiltonians yield improved results compared with the original ones when they are employed for nodal structure searching, surface Green's function calculations, and other model calculations., 22 pages, 7 figures, WannSymm code can be downloaded from https://github.com/ccao/WannSymm ; typos corrected, references added

Topological crystalline metals and semimetals (TCMs) have stimulated great research interest, which broadens the classification of topological phases and provides a valuable platform to explore topological superconductivity. Here, we report the discovery of superconductivity and topological features in Pb-intercalated transition-metal dichalcogenide ${\mathrm{Pb}}_{1/3}\mathrm{Ta}{\mathrm{S}}_{2}$. Systematic measurements indicate that ${\mathrm{Pb}}_{1/3}\mathrm{Ta}{\mathrm{S}}_{2}$ is a quasi-two-dimensional (q-2D) type-II superconductor ($T{}_{c}\ensuremath{\approx}2.8$ K) with a significantly enhanced anisotropy of upper critical field (${\ensuremath{\gamma}}_{{H}_{c2}}={H}_{c2}^{ab}/{H}_{c2}^{c}\phantom{\rule{4pt}{0ex}}\ensuremath{\approx}17$). In addition, first-principles calculations reveal that ${\mathrm{Pb}}_{1/3}\mathrm{Ta}{\mathrm{S}}_{2}$ hosts multiple topological Dirac fermions in the electronic band structure. We discover four groups of Dirac nodal lines on the ${k}_{z}=\ensuremath{\pi}$ plane and two sets of Dirac points on the rotation or screw axes, which are protected by crystalline symmetries and robust against spin-orbit coupling (SOC). Dirac-cone-like surface states emerge on the (001) surface because of band inversion. Our work shows that the TCM candidate ${\mathrm{Pb}}_{1/3}\mathrm{Ta}{\mathrm{S}}_{2}$ is a promising arena to study the interplay between superconductivity and topological Dirac fermions.

We investigated the coexistence of superconductivity and antiferromagnetic order in the compound Er$_{2}$O$_{2}$Bi with anti-ThCr$_{2}$Si$_{2}$-type structure through resistivity, magnetization, specific heat measurements and first-principle calculations. The superconducting transition temperature $T_{\rm c}$ of 1.23 K and antiferromagnetic transition temperature $T_{\rm N}$ of 3 K are observed in the sample with the best nominal composition. The superconducting upper critical field $H_{\rm c2}$(0) and electron-phonon coupling constant $\lambda$$_{e-ph}$ in Er$_{2}$O$_{2}$Bi are similar to those in the previously reported non-magnetic superconductor Y$_{2}$O$_{2}$Bi with the same structure, indicating that the superconductivity in Er$_{2}$O$_{2}$Bi may have the same origin as in Y$_{2}$O$_{2}$Bi. The first-principle calculations of Er$_{2}$O$_{2}$Bi show that the Fermi surface is mainly composed of the Bi 6$p$ orbitals both in the paramagnetic and antiferromagnetic state, implying minor effect of the 4$f$ electrons on the Fermi surface. Besides, upon increasing the oxygen incorporation in Er$_{2}$O$_{x}$Bi, $T_{\rm c}$ increases from 1 to 1.23 K and $T_{\rm N}$ decreases slightly from 3 to 2.96 K, revealing that superconductivity and antiferromagnetic order may compete with each other. The Hall effect measurements indicate that hole-type carrier density indeed increases with increasing oxygen content, which may account for the variations of $T_{\rm c}$ and $T_{\rm N}$ with different oxygen content.

Coexistence of topological bands and charge density wave (CDW) in topological materials has attracted immense attentions because of their fantastic properties, such as axionic-CDW, three-dimensional quantum Hall effect, etc. In this work, a nodal-line semimetal InxTaS2 characterized by CDW and superconductivity is successfully synthesized, whose structure and topological bands (two separated Wely rings) are similar to In0.58TaSe2. A 2 x 2 commensurate CDW is observed at low temperature in InxTaS2, identified by transport properties and STM measurements. Moreover, superconductivity emerges below 0.69 K, and the anisotropy ratio of upper critical field [Gamma = H||ab c2(0)=H||c c2(0)] is significantly enhanced compared to 2H-TaS2, which shares the same essential layer unit. According to the Lawrence-Doniach model, the enhanced Gamma may be explained by the reduced effective mass in kx-ky plane, where Weyl rings locate. Therefore, this type of layered topological systems may offer a platform to investigate highly anisotropic superconductivity and to understand the extremely large upper critical field in the bulk or in the two-dimensional limit., Comment: Accepted for publication in PRB

Inputs of nitrogen into terrestrial ecosystems, mainly via the use of ammonium-based fertilizers in agroecosystems, are enormous, but the fate of this nitrogen under elevated atmospheric carbon dioxide (CO2) is not well understood. We have taken advantage of a 15-year free-air CO2 enrichment study to investigate the influence of elevated CO2 on the transformation of ammonium-nitrogen in a rice ecosystem in which ammonium is usually assumed to be stable under anaerobic conditions. We demonstrate that elevated CO2 causes substantial losses of ammonium-nitrogen that result from anaerobic oxidation of ammonium coupled to reduction of iron. We identify a new autotrophic member of the bacterial order Burkholderiales that may use soil CO2 as a carbon source to couple anaerobic ammonium oxidation and iron reduction. These findings offer insight into the coupled cycles of nitrogen and iron in terrestrial ecosystems and raise questions about the loss of ammonium-nitrogen from arable soils under future climate-change scenarios.

Superconductivity in crystals without inversion symmetry has received extensive attention due to its unconventional pairing and possible nontrivial topological properties. Using first-principles calculations, we systemically study the electronic structure of noncentrosymmetric superconductors A2Cr3As3 (A = Na, K, Rb, and Cs). Topologically protected triply degenerate points connected by one-dimensional arcs appear along the C3 axis, coexisting with strong ferromagnetic (FM) fluctuations in the non-superconducting state. Within random phase approximation, our calculations show that strong enhancements of spin fluctuations are present in K2Cr3As3 and Rb2Cr3As3 and are substantially reduced in Na2Cr3As3 and Cs2Cr3As3. Symmetry analysis of pairing gap Δ(k) and spin–orbit coupling gk suggest that the arc surface states may also exist in the superconducting state, giving rise to possible nontrivial topological properties.

Inputs of nitrogen into terrestrial ecosystems, mainly via the use of ammonium-based fertilizers in agroecosystems, are enormous, but the fate of this nitrogen under elevated atmospheric carbon dioxide (CO

We investigate the electronic structure of nickelate superconductor NdNiO2 upon hole doping, by means of density-functional theory and dynamical mean-field theory. We demonstrate the strong intrinsic hybridization between strongly correlated states formed by Ni-3dx2-y2 orbital and itinerant electrons due to Nd-5d and Ni-3dz2 orbitals, producing a valence-fluctuating correlated metal as the normal state of hole-doped NdNiO2. The Hund's rule appears to play a dominating role on multi-orbital physics in the lightly doped compound, while its effect is gradually reduced by increasing the doping level. Crucially, the hole-doping leads to intricate effects on Ni-3d orbitals, such as a non-monotonic change of electron occupation in lightly doped level, and a flipping orbital configuration in the overdoped regime. Additionaly, we also map out the topology of Fermi surface at different doping levels. These findings render a preferred window to peek into electron pairing and superconductivity., Comment: 6 pages, 4 figures. 4 supply pages

Significance The 3D nodal points in Dirac and/or Weyl semimetals are in the vanguard of quantum materials research. A hallmark of these systems is the linear band dispersion. This latter electronic stricture gives rise to unconventional transport and optical phenomena. Here, we demonstrate that solids with dispersive nodal lines in the electronic structure share many common aspects with the response of 3D nodal-points systems. We investigated N b A s 2 using a combination of optical and magneto-optical techniques and have identified electromagnetic signature of dispersive nodal lines. This particular compound has allowed us to inquire the impact of spin-orbit coupling on the universal characteristic of nodal metals.

As the new display technology, Micro-LEDs are of the advantages of low power consumption, high brightness, high resolution and fast response time. However, the strong surface non-radiative recombination significantly reduces their efficiency. Some techniques such as epitaxial growth or wet sulfide have been introduced to inhibit the surface recombination, but these expensive or unstable methods ignore the operability of industrial production. Herein, we use an ion implantation method to modify the high-density surface defects on the sidewall, thereby improve the luminous efficiency effectively by inhibiting carrier surface non-radiative recombination. The photoelectric performances of GaN-based Micro-LEDs after N ion implantation were studied. The characterization results indicated that the photoluminescence intensity of Micro-LEDs was increased by 7 times after passivation, which was attributed to the significant elimination of sidewall damage. In addition, the removal of the surface dangling bonds and oxidized nitrides (Ga–N or Ga-OH bonds) after the passivation process were further proved by Auger electron spectroscopy characterization. As a result of the N ion implantation, the external quantum efficiency of packaged Micro-LEDs chip increased about 33%. Therefore, this manuscript will provide a new direction for improving the photoelectric performance of Micro-LEDs.

BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects.This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUCThe pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUCIn this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion.NCT03030430.

The relationship between magnetism and superconductivity has been one of the most discussed topics in iron-based superconductors. Using first-principles calculations, we have studied the electronic structure of 1144-type iron-based superconductor EuRbFe4As4. We find the crystal field splitting of EuRbFe4As4 is unique, such that the $$d_{z^2}$$ d z 2 orbitals are closer to the Fermi level $$\epsilon _{\mathrm F}$$ ϵ F than the dxy orbitals. The Ruderman−Kittel−Kasuya−Yosida (RKKY) interaction strength is approximately 0.12 meV in pristine EuRbFe4As4. Upon Ni-doping on the Fe site, the RKKY interaction strength is barely changed upon Ni-doping due to the highly anisotropic Fermi surfaces and multiband effect, despite the drastically reduced dzx(y) density of state at $$\epsilon _{\mathrm F}$$ ϵ F . Finally, in both pristine and doped compounds, the RKKY interaction is primarily mediated through bands due to Fe-$$d_{z^2}$$ d z 2 orbitals. Our calculations suggest the RKKY interaction mediated by $$d_{z^2}$$ d z 2 orbital is probably responsible for the magnetism in EuRbFe4As4 and doesn’t change upon Ni-doping.

The micro lighting-emitting diode (Micro-LED) array devices have attracted attention due to increasing demand in augmented reality (AR), virtual reality (VR), LIFI light source, and other micro-display applications. However, with the decrease of micro-LED diameter, the performance of micro-LED is severely limited due to the size effect. In the work, the AlGaInP based red micro-LED with diameter ranging from 2 to 16 μm was prepared to study the size effect of micro-LED array, the array with larger micro-LED diameter show higher external quantum efficiency (EQE), meanwhile, the carrier lifetime decrease with the decreasing of the diameter, which can be explained by more surface states in the micro-LED with smaller diameter. The enhancement of EQE by 2 times has been achieved after surface passivation in (NH4)2Sx solution.

Purpose: In this paper, the authors proposed a new 3D registration algorithm, 3D-scale invariant feature transform (SIFT)-Flow, for multiatlas-based liver segmentation in computed tomography (CT) images. Methods: In the registration work, the authors developed a new registration method that takes advantage of dense correspondence using the informative and robust SIFT feature. The authors computed the dense SIFT features for the source image and the target image and designed an objective function to obtain the correspondence between these two images. Labeling of the source image was then mapped to the target image according to the former correspondence, resulting in accurate segmentation. In the fusion work, the 2D-based nonparametric label transfer method was extended to 3D for fusing the registered 3D atlases. Results: Compared with existing registration algorithms, 3D-SIFT-Flow has its particular advantage in matching anatomical structures (such as the liver) that observe large variation/deformation. The authors observed consistent improvement over widely adopted state-of-the-art registration methods such as ELASTIX, ANTS, and multiatlas fusion methods such as joint label fusion. Experimental results of liver segmentation on the MICCAI 2007 Grand Challenge are encouraging, e.g., Dice overlap ratio 96.27% ± 0.96% by our method compared with the previous state-of-the-art result of 94.90% ± 2.86%. Conclusions: Experimental results show that 3D-SIFT-Flow is robust for segmenting the liver from CT images, which has large tissue deformation and blurry boundary, and 3D label transfer is effective and efficient for improving the registration accuracy.

We report a topological semimetal ${\mathrm{W}}_{2}{\mathrm{As}}_{3}$ with a space group $C2/m$. Based on the first-principles calculations, band crossings are partially gapped when spin-orbit coupling is included. The ${Z}_{2}$ indices at the electron filling are [1;111], characterizing a strong topological insulator and topological surface states. From the magnetotransport measurements, nearly quadratic field dependence of magnetoresistance (MR) ($B\ensuremath{\parallel}[200]$) at 3 K indicates an electron-hole compensated compound whose longitudinal MR reaches 11 500% at 3 K and 15 T. In addition, multiband features are detected from the high-magnetic-field Shubnikov--de Haas (SdH) oscillation, Hall resistivity, and band calculations. A nontrivial $\ensuremath{\pi}$ Berry's phase is obtained, suggesting the topological feature of this material. A two-band model can fit well the conductivity and Hall coefficient. Our experiments manifest that the transport properties of ${\mathrm{W}}_{2}{\mathrm{As}}_{3}$ are in good agreement with the theoretical calculations.

In a compelling study, Hicks Pries et al . (Reports, 31 March 2017, p. 1420) showed that 4°C warming enhanced soil CO 2 production in the 1-meter soil profile, with all soil depths displaying similar temperature sensitivity (Q 10 ). We argue that some caveats can be identified in their experimental approach and analysis, and that these critically undermine their conclusions and hence their claim that the strength of feedback between the whole-soil carbon and climate has been underestimated in terrestrial models.

The superoxide dismutases (SODs) are important antioxidant enzymes to remove excess biologically reactive oxygen intermediates, and thus avoid adverse conditions. In this study, an extracellular copper–zinc superoxide dismutase (ecCuZnSOD) gene and a mitochondrial manganese superoxide dismutase (mtMnSOD) gene were cloned from hemocytes of the freshwater crayfish, Procambarus clarkii . The open reading frame (ORF) of ecCuZnSOD is 612 bp encoding a 204 amino acid (aa) protein with a 24 aa signal peptide, whereas the ORF of mtMnSOD is 654 bp and encodes a 218 aa protein with a 20 aa mitochondrial-targeting sequence in the N-terminus. P. clarkii ecCuZnSOD and mtMnSOD proteins showed high similarity with ecCuZnSODs and mtMnSODs from other crustaceans, respectively. Both ecCuZnSOD and mtMnSOD of P. clarkii were highly expressed in hepatopancreas, hemocytes and gill; lower expression levels were seen in intestine, stomach, nerve, heart and muscle. The mRNA expressions of three SODs of P. clarkii (ecCuZnSOD, mtMnSOD and cytosolic MnSOD (cytMnSOD)) were studied after Spiroplasma eriocheiris and Aeromonas hydrophila stimulations. After S. eriocheiris challenge, the mRNAs of three SODs in hemocytes and gill were up-regulated, and ecCuZnSOD also increased in the hepatopancreas. However, the mtMnSOD and cytosolic MnSOD in the hepatopancreas were down-regulated. After A. hydrophila challenge, the mRNA expressions of three SODs in hepatopancreas and hemocytes were up-regulated and down-regulated in gill. The total SOD activity and CuZnSOD activity were increased compared to the control group with both S. eriocheiris and A. hydrophila challenges. The results may indicate that the SODs of P. clarkii have important roles in innate immune responses against S. eriocheiris and A. hydrophila .

In this paper, the authors proposed a new 3D registration algorithm, 3D-scale invariant feature transform (SIFT)-Flow, for multiatlas-based liver segmentation in computed tomography (CT) images.In the registration work, the authors developed a new registration method that takes advantage of dense correspondence using the informative and robust SIFT feature. The authors computed the dense SIFT features for the source image and the target image and designed an objective function to obtain the correspondence between these two images. Labeling of the source image was then mapped to the target image according to the former correspondence, resulting in accurate segmentation. In the fusion work, the 2D-based nonparametric label transfer method was extended to 3D for fusing the registered 3D atlases.Compared with existing registration algorithms, 3D-SIFT-Flow has its particular advantage in matching anatomical structures (such as the liver) that observe large variation/deformation. The authors observed consistent improvement over widely adopted state-of-the-art registration methods such as ELASTIX, ANTS, and multiatlas fusion methods such as joint label fusion. Experimental results of liver segmentation on the MICCAI 2007 Grand Challenge are encouraging, e.g., Dice overlap ratio 96.27% ± 0.96% by our method compared with the previous state-of-the-art result of 94.90% ± 2.86%.Experimental results show that 3D-SIFT-Flow is robust for segmenting the liver from CT images, which has large tissue deformation and blurry boundary, and 3D label transfer is effective and efficient for improving the registration accuracy.

The electronic structures and topological properties of transition metal dipnictides $XP{n}_{2}$ ($X\phantom{\rule{0.28em}{0ex}}=\phantom{\rule{0.28em}{0ex}}\mathrm{Ta}$, Nb; $Pn\phantom{\rule{0.28em}{0ex}}=\phantom{\rule{0.28em}{0ex}}\mathrm{P}$, As, Sb) have been systematically studied using first-principles calculations. In addition to small bulk Fermi surfaces, the band anticrossing features near the Fermi level can be identified from band structures without spin-orbit coupling, leading to nodal lines in all these compounds. Inclusion of spin-orbit coupling gaps out these nodal lines, leaving only a pair of disentangled electron/hole bands crossing the Fermi level. Therefore, the low-energy physics can be in general captured by the corresponding two-band model with several isolated small Fermi pockets. Detailed analysis of the Fermi surfaces suggests that the arsenides and ${\mathrm{NbSb}}_{2}$ are nearly compensated semimetals while the phosphorides and ${\mathrm{TaSb}}_{2}$ are not. Based on the calculated band parities, the electron and hole bands are found to be weakly topological nontrivial, giving rise to surface states. As an example, we presented the surface-direction-dependent band structure of the surfaces states in ${\mathrm{TaSb}}_{2}$.

Oligonucleotides containing CpG motifs (CpG ODN) are strong adjuvants for humoral and cellular immune responses in mice, and innate defense-regulator peptides (IDRs) are known to facilitate the uptake of antigens into antigen presenting cells (APCs), but data on synergistic effects of CpG and IDRs in piglets are scarce. In this report, the combination of porcine-specific CpG ODN and HH2 (a kind of IDR which was selected for its better synergy with CpG ODN) was used as immunoadjuvant to enhance the immune responses of the newborn piglets to Pseudorabies attenuated virus (PRV) vaccine. The titers of specific antibodies and serum IgG1/IgG2 subtypes to PRV vaccine, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-12 and IL-4 were examined to identify the immune responses of the newborn piglets. The results showed that piglets immunized intranasally (IN) and subcutaneously (SC) with PRV vaccine and CpG-HH2 complex both presented high titers of PRV-specific antibodies and IgG2 isotype, a Th1-dominated (IFN-γ and IL-12) cytokine profiles, high levels of IgA in saliva, broncheoalveolar lavage (BAL) and intestinal washings. The results suggested that, CpG-HH2 complex augmented systemic (IgG in serum) and mucosal (IgA in saliva, BAL and intestinal washings) immune responses against antigen. CpG-HH2 complex stimulated both T-helper type1 (Th1) (IgG2) and Th2 (IgA) responses when delivered IN, and IN route could induce stronger mucosal immune responses than SC route. All these data indicate that CpG-HH2 complex is a potential effective adjuvant for the PRV vaccine in newborn piglets.

CpG oligodeoxynucleotide (CpG ODN) has been described as an effective activator of the innate immune system, with potential to protect against infection caused by a range of pathogens in a non-specific manner. We therefore investigated if intranasal (IN), oral (OR)-mucosal, and intramuscular (IM)-systemic administrations of CpG ODN without antigen codelivery could all enhance innate immunity in the enteric mucosa and control the extent of enterotoxigenic Escherichia coli (ETEC) infection in weaning piglets. Here our data showed that CpG ODN dosed by IN, OR or IM routes protected weaning piglets against a subsequent challenge with ETEC. The level of protection was greater when CpG ODN was administered IN and OR than IM, demonstrating a clear relationship between the route of CpG dosing and protection. IN and OR treatments with CpG ODN reduced bacterial load in the phases at days 3-5 post challenge. The CXC chemokine (CXCL10 and CXCL11) and CC chemokine (CCL4 and CCL5) mRNA expressions were elevated in the intestinal tissues from animals treated IN or OR with CpG ODN compared to untreated controls. Significantly enhanced mRNA expressions for cathelicidins (PR-39 and protegrin-1), but moderately for β-defensin (pBD1 and pBD2), were observed in IN or OR CpG-treatments. Also, significant production of cytokines (IL-12, IFN-γ, and MCP-1) and F4-specific antibodies (IgG/IgA) was detected in intestinal washings following IN and OR CpG-treatments. In contrast, IM delivery induced marked production of sera F4-specific antibodies. It was possible that these chemokines, cytokines, cathelicidins and antibodies played a role in the clearance of ETEC. These findings suggested that IN or OR administration of CpG ODN without antigen codelivery might represent a valuable strategy for induction of innate immunity against ETEC infection.

The in vivo immunoadjuvant effects of CpG oligodeoxynucleotides (CpG-ODN) have been studied extensively in mice and relatively fewer studies have been done in piglets. But so far, the innate immunostimulatory effects of CpG-ODN combination with innate defense-regulator peptides (IDRs) have not been demonstrated. The purpose of this study is to determine the potential effects of CpG-ODN with IDR in newborn piglets. The immunostimulatory abilities of four selected IDRs were compared, among them HH2 showed best immunostimulatory effects in newborn piglets. Hereafter, the abilities of CpG-ODN combined with HH2 to enhance innate immune responses were examined in newborn piglets. The complex of HH2 and CpG-ODN could induce much stronger Th1 cytokine and chemokine responses than HH2 or CpG-ODN alone. HH2-CpG-ODN immunized piglets showed higher B cell percentage in PBMCs than CpG-ODN alone. These in vivo data demonstrated for the first time that subcutaneously (SC) administration of CpG-ODN combined with HH2 is efficient to stimulate innate immune system in newborn piglets.

Oligonucleotides containing CpG motifs (CpG ODN) are known to be potent stimulators of the innate immune system in vitro and in vivo. We therefore investigated if intranasal (IN)-mucosal or intramuscular (IM)-systemic administration of CpG ODN could enhance innate immunity in the intestinal mucosa and peripheral blood mononuclear cells (PBMCs) in piglets. Repeated IN or IM administration of CpG ODN significantly increased local/systemic mRNA expression of the CC chemokines macrophage inflammatory protein 1beta (MIP-1beta) and monocyte chemoattractant protein-1 (MCP-1) and CXC chemokine gamma interferon-inducible protein 10 (IP-10) and percentages of macrophages and cDCs in the intestine (jejunum, caecum and colon) and PBMCs by different kinetics. IN delivery of CpG ODN induced much stronger chemokine responses than IM delivery at intestinal mucosas, whereas IN delivery of CpG ODN induced some weaker chemokine responses than IM delivery in PBMCs. These findings suggest that IN administration of 100mug/kg-CpG ODN without antigen codelivery may represent a valuable strategy for induction of innate immunity against infection.