Boosting the immune response in COVID-19 vaccines via an Alum:CpG complex adjuvant.

Selecting appropriate adjuvants is crucial for developing an effective vaccine. However, studies on the immune responses triggered by different adjuvants in COVID-19 inactivated vaccines are scarce. Herein, we evaluated the efficacy of Alum, CpG HP021, Alum combined with CpG HP021 (Alum/CpG), or MF-59 adjuvants with COVID-19 inactivated vaccines in K18-hACE2 mice, and compared the different immune responses between K18-hACE2 and BALB/c mice. In K18-hACE2 mice, the Alum/CpG group produced a 6.5-fold increase in anti-receptor-binding domain (RBD) IgG antibody titers compared to the Alum group, and generated a comparable level of antibodies even when the antigen amount was reduced by two-thirds, possibly due to the significant activation of germinal center (GC) structures in the central region of the spleen. Different adjuvants induced a variety of binding antibody isotypes. CpG HP021 and Alum/CpG were biased towards Th1/IgG2c, while Alum and MF-59 were biased toward Th2/IgG1. Cytokines IFN-γ, IL-2, and TNF-α were significantly increased in the culture supernatants of splenocytes specifically stimulated in the Alum/CpG group. The antibody responses in BALB/c mice were similar to those in K18-hACE2 mice, but with lower levels of neutralizing antibodies (NAbs). Notably, the Alum/CpG-adjuvanted inactivated vaccine induced a higher number of T cells secreting IFN-γ and IL-2, increased the percentage of effector memory T (TEM) cells among CD8+ T cells, and effectively protected K18-hACE2 mice from Delta variant challenge. Our results showed that Alum/CpG complex adjuvant significantly enhanced the immune response to inactivated COVID-19 antigens and could induce a long-lasting immune response.

Optical Force Effects of Rayleigh Particles by Cylindrical Vector Beams.

High-order cylindrical vector beams possess flexible spatial polarization and exhibit new effects and phenomena that can expand the functionality and enhance the capability of optical systems. However, building a general analytical model for highly focused beams with different polarization orders remains a challenge. Here, we elaborately develop the vector theory of high-order cylindrical vector beams in a high numerical aperture focusing system and achieve the vectorial diffraction integrals for describing the tight focusing field with the space-variant distribution of polarization orders within the framework of Richards-Wolf diffraction theory. The analytical formulae include the exact three Cartesian components of electric and magnetic distributions in the tightly focused region. Additionally, utilizing the analytical formulae, we can achieve the gradient force, scattering force, and curl-spin force exerted on Rayleigh particles trapped by high-order cylindrical vector beams. These results are crucial for improving the design and engineering of the tightly focused field by modulating the polarization orders of high-order cylindrical vector beams, particularly for applications such as optical tweezers and optical manipulation. This theoretical analysis also extends to the calculation of complicated optical vortex vector fields and the design of diffractive optical elements with high diffraction efficiency and resolution.

Enhancing computational holography with spiral phase coding.

In this Letter, we propose a new, to the best of our knowledge, approach to generate computer-generated holograms (CGHs) utilizing spiral phase coding. This method can be applied to generate an array spiral phase plate that can generate array vortex spots with a high compression ratio. Moreover, the method extends its applicability to the generation of Fresnel holograms and kinoforms, resulting in edge-enhanced imaging. Theoretical analysis and experimental results demonstrate the potential of spiral phase-encoded CGHs in laser processing and image enhancement.

Far-field mid-infrared microscopy via spatial frequency shifting of evanescent waves in photorefractive nematic liquid crystal.

Mid-infrared wavelength has unique advantages in revealing the nanostructures and molecular vibrational signatures. However, the mid-infrared subwavelength imaging is also limited by diffraction. Here, we propose a scheme for breaking the limitation in mid-infrared imaging. With the assistance of orientational photorefractive grating established in nematic liquid crystal, evanescent waves are efficiently shifted back into the observation window. The visualized propagation of power spectra in k-space also proves this point. The resolution has an improvement about 3.2 times higher than the linear case, showing potentials in various imaging areas, such as biological tissues imaging and label-free chemical sensing.

A multiplex TaqMan real-time RT-PCR assay for the simultaneous detection of H4, H6, and H10 avian influenza viruses.

Avian influenza viruses (AIVs) have caused a large number of epidemics in domestic and wild birds, and even posed a health challenge to humans. Highly pathogenic AIVs have attracted the most public attention. However, low pathogenic AIVs, including H4, H6, and H10 subtype AIVs, have spread covertly in domestic poultry, without obvious clinical signs. The emergence of human infections with H6 and H10 AIVs and the evidence of seropositivity of H4 AIV in poultry-exposed individuals indicated that these AIVs sporadically infect humans and could cause a potential pandemic. Therefore, a rapid and sensitive diagnostic method to simultaneously detect Eurasian lineage H4, H6, and H10 subtype AIVs is urgently required. Four singleplex real-time RT-PCR (RRT-PCR) assays were established based on carefully designed primers and probes of the conserved regions of the matrix, H4, H6, and H10 genes and combined into a multiplex RRT-PCR method to simultaneously detect H4, H6, and H10 AIVs in one reaction. The detection limit of the multiplex RRT-PCR method was 1-10 copies per reaction when detecting standard plasmids, and showed no cross-reaction against other subtype AIVs and other common avian viruses. Additionally, this method was suitable to detect the AIVs in samples from different sources, the results of which showed high consistency with virus isolation and a commercial influenza detection kit. In summary, this rapid, convenient, and practical multiplex RRT-PCR method could be applied in laboratory testing and clinical screening to detect AIVs.

Evaluation of panel of neutralising murine monoclonal antibodies and a humanised bispecific antibody against influenza A(H1N1)pdm09 virus infection in a mouse model.

The influenza A (H1N1) pdm09 virus attracted public attention because of its high prevalence. The annual global morbidity and mortality rates of influenza remain high despite the application of influenza vaccines and antiviral drugs, which indicates the urgent need to identify a more effective strategy for controlling and treating A(H1N1) pdm09 influenza infection. To produce a highly effective therapeutic with broad specificity for A(H1N1) pdm09 influenza viruses, we generated 15 murine monoclonal antibodies (mAbs) via hybridoma technology: 11 mAbs demonstrated 20-100% therapeutic protection in a mouse model of A(H1N1) pdm09 infection at a single dose of 10 mg/kg. A humanised bispecific antibody (Bis-Hu11-1) generated based on the mAbs 3D2 and 3D11, combining the specificities of the two mAbs, was also effective in preventing and treating A(H1N1) pdm09 infection in a mouse model. Bis-Hu11-1 demonstrated hemagglutination inhibition (HI) activity against the escape mutants generated by its parental mAbs that resulted in the obvious reduction in the HI activity of the parental mAbs. In summary, we generated a panel of neutralising mAbs against A(H1N1) pdm09 influenza virus. This study presents a promising method for developing neutralising antibodies that potentially target a series of antigenically diverse influenza viruses.

Generation and characterization of monoclonal antibodies against the hemagglutinin of H3N2 influenza A viruses.

Seasonal influenza viruses are highly contagious, leading to 290,000-650,000 mortalities every year globally. Among the influenza viruses, influenza A virus (H3N2) has attracted much attention due to its high frequency of antigenic variations, resulting in poor protection by vaccination. We generated a panel of murine neutralizing monoclonal antibodies (mAbs) against A/Texas/50/2012 (H3N2) and identified the relevant epitopes that potentially influence the antigenicity by selecting mAb-resistant mutants. The epitopes were mainly in antigenic site A (1/9, 11.1%), B (6/9, 66.7%), and C (1/9, 11.1%), which is consistent with recent reports on the immunodominance of antigenic site B. The amino acid substitutions at positions 156, 157, 159, 160, and 189 at antigenic site B resulted in decreased mAb capability for blocking receptor binding. In addition, the neutralizing spectra of three mAbs (1F8, 1G9 and 1H5) were different, suggesting that their epitopes may be different but partially overlapping, and it required further study. Further, the mAb 3F9 selected a new substitution, D53G/N, at antigenic site C and showed in vitro neutralizing activity against A/Victoria/361/2011 (H3N2), A/Texas/50/2012 (H3N2), and A/Hong Kong/2671/2019 (H3N2), suggesting a potential epitope on H3 hemagglutinin for inducing broad neutralizing antibody responses. Continuous research and regular monitoring of novel epitopes are of great importance for improving vaccine strain selection.

Controllable perfect optical vortex generated by complex amplitude encoding.

We propose a new paradigm for generating the perfect optical vortex (POV) with a controlled structure and orbital angular momentum (OAM) distribution in the focal region of a tightly focused system. The superiority of the proposed technique is demonstrated with an experiment involving the dynamic manipulation of small particles. This technique for creating the POV could open new routes to optical manipulation based on OAM.

A multiplex real-time RT-PCR method for detecting H5, H7 and H9 subtype avian influenza viruses in field and clinical samples.

In recent years, H5 and H7 subtypes of highly pathogenic avian influenza viruses (HPAIVs) have been identified in poultry worldwide, resulting in large economic losses to poultry production. Furthermore, H9N2 low pathogenic AIVs are reported to provide internal genes for generating novel reassortant AIVs, leading to potential pandemic risks. To establish an accurate, sensitive and convenient diagnostic method for H5, H7 and H9 subtype AIVs in Eurasian lineage, four groups of specific primers and probes were designed based on the conserved fragments of M, H5, H7 and H9 genes, and a multiplex real-time RT-PCR (RRT-PCR) method was established. High sensitivity was achieved for the multiplex RRT-PCR approach, with a detection limit of 1-10 copies (plasmid DNA) per reaction. The specificity of the method was evaluated using diverse subtypes of AIVs and other avian respiratory viruses isolated in eastern China over the last 9 years. Compared with virus isolation, a higher consistency was achieved when assessing 135 field samples and 126 clinical samples. The results showed that the multiplex RRT-PCR method is a fast, convenient and practical method for AIV clinical detection and epidemiological analysis.

Nonlinear super-resolution imaging via orientationally enhanced photorefractive effect in polymer.

Resulting from the attenuation of evanescent waves in imaging, conventional microscopy techniques always yield few subwavelength features. In this Letter, a nonlinear far-field super-resolution technique is investigated, which is theoretically beyond the linear diffraction limitation. Based on the orientationally enhanced photorefractive effect of polymer, an inherently phase-matched diffraction grating is established and generates daughter modes by wave mixture. Almost all of these modes can pass through a finite-aperture filter and be sensed for reconstruction. An improvement of resolution of about four times is obtained and expected to be increased further. This work may provide a potential strategy for various subwavelength-resolved imaging applications.

The MSP-RON pathway regulates liver fibrosis through transforming growth factor beta-dependent epithelial-mesenchymal transition.

BACKGROUND: Liver fibrosis is pathologically important in the liver cirrhosis progression. The epithelial-mesenchymal transition (EMT) is crucial for organ fibrosis. Macrophage-stimulating protein (MSP) and its receptor tyrosine kinase, RON, promote cellular EMT. However, their role in liver fibrosis is unclear. Here, we clarify the biological profile, potential mechanisms and therapeutic targets of the MSP-RON pathway in liver fibrosis. MATERIALS AND METHODS: Macrophage-stimulating protein expression and its correlation with clinicopathological characteristics of cirrhosis were evaluated in 57 clinical cases and a control group. The effect of MSP-RON pathway in liver fibrosis was determined in vitro and in vivo. The therapeutic effects of MSP or RON inhibition on liver fibrosis were evaluated in a mouse liver fibrosis model. RESULTS: Macrophage-stimulating protein is upregulated in liver cirrhosis, which was associated with poor patient prognosis. The MSP-RON pathway promoted hepatocytes EMT. MSP-RON-induced EMT depends on the transforming growth factor beta (TGF-ß) pathway and is regulated by TGF-ß inhibitors. In animal models, an MSP blocking antibody and a small molecule inhibitor of RON, BMS-777607, both inhibited liver fibrosis progression. CONCLUSION: Our study revealed that MSP is an important biomarker in liver cirrhosis progression and can be used to prognose patients. The MSP-RON pathway promotes the EMT of hepatocytes and the progress of fibrosis via a TGF-ß related pathway. Consequently, we identified a new treatment strategy for liver cirrhosis through targeted inhibition of MSP/RON. This research increases the understanding of EMT-modulated liver fibrosis and provides new insights into biomarkers and therapeutic targets of liver fibrosis.

3D high precision laser printing of a flat nanofocalizer for subwavelength light spot array.

Here, we demonstrate a flat nanofocalizer for converging light field into a uniform subwavelength light spot array based on the fractional Talbot effect by developing a direct laser writing technique with 3D fabrication precision. The fractional Talbot effect endows the device with the merits of high compression ratio and modular design capability for transforming a plane wave into arrayed light focal spots. By combining a synergistic laser printing technique, we introduce a buffer layer for improving the fabrication precision of structural height in favor of accurately manipulating the phase delay. For a given light wavelength at 750 nm, by precisely producing a nanofocalizer consisting of periodic unit elements with the dimensions of 300(width)×600(length)×585(height)nm, we have achieved 5×6 light spot array with modular design, while the full width at half-maximum of a single focused light spot can be reduced to ∼0.82λ. Our research may pave the way for realizing subwavelength optical devices capable of being readily integrated to existing optical systems.

π-phase modulated monolayer supercritical lens.

The emerging monolayer transition metal dichalcogenides have provided an unprecedented material platform for miniaturized opto-electronic devices with integrated functionalities. Although excitonic light-matter interactions associated with their direct bandgaps have received tremendous research efforts, wavefront engineering is less appreciated due to the suppressed phase accumulation effects resulting from the vanishingly small thicknesses. By introducing loss-assisted singular phase behaviour near the critical coupling point, we demonstrate that integration of monolayer MoS2 on a planar ZnO/Si substrate, approaching the physical thickness limit of the material, enables a π phase jump. Moreover, highly dispersive extinctions of MoS2 further empowers broadband phase regulation and enables binary phase-modulated supercritical lenses manifesting constant sub-diffraction-limited focal spots of 0.7 Airy units (AU) from the blue to yellow wavelength range. Our demonstrations downscaling optical elements to atomic thicknesses open new routes for ultra-compact opto-electronic systems harnessing two-dimensional semiconductor platforms with integrated functionalities.

Highly Efficient Multiview Depth Coding Based on Histogram Projection and Allowable Depth Distortion.

Mismatches between the precisions of representing the disparity, depth value and rendering position in 3D video systems cause redundancies in depth map representations. In this paper, we propose a highly efficient multiview depth coding scheme based on Depth Histogram Projection (DHP) and Allowable Depth Distortion (ADD) in view synthesis. Firstly, DHP exploits the sparse representation of depth maps generated from stereo matching to reduce the residual error from INTER and INTRA predictions in depth coding. We provide a mathematical foundation for DHP-based lossless depth coding by theoretically analyzing its rate-distortion cost. Then, due to the mismatch between depth value and rendering position, there is a many-to-one mapping relationship between them in view synthesis, which induces the ADD model. Based on this ADD model and DHP, depth coding with lossless view synthesis quality is proposed to further improve the compression performance of depth coding while maintaining the same synthesized video quality. Experimental results reveal that the proposed DHP based depth coding can achieve an average bit rate saving of 20.66% to 19.52% for lossless coding on Multiview High Efficiency Video Coding (MV-HEVC) with different groups of pictures. In addition, our depth coding based on DHP and ADD achieves an average depth bit rate reduction of 46.69%, 34.12% and 28.68% for lossless view synthesis quality when the rendering precision varies from integer, half to quarter pixels, respectively. We obtain similar gains for lossless depth coding on the 3D-HEVC, HEVC Intra coding and JPEG2000 platforms.

Improved electrochemical performance of 2D accordion-like MnV2O6 nanosheets as anode materials for Li-ion batteries.

MnV2O6 is a promising anode material for lithium ion batteries with high theoretical specific capacity, abundant reserves and inexpensive constituent elements. However, in the process of lithization and de-lithization, the MnV2O6 anode material will form an amorphous phase, leading to collapse of its original layered structure; this greatly decreases its lithium storage capacity and specific capacity and affects its long-term cycle performance. In this study, 2D accordion-like MnV2O6 nanosheets with Co-doping are obtained via a hydrothermal route. The cobalt ions partially replace the positions of the manganese ions, and the emergence of Co3+ ions is inferred to induce the formation of a built-in electric field in the electrode to enhance the electrochemical behaviour of MnV2O6, presenting a high capacity of 1005.9 mA h g-1 after hundreds of cycles. The capacitive contribution to the total capacity is investigated to obtain insight into the kinetic analysis of its electrochemical behaviour. This study sheds light on an effective strategy to obtain excellent electrochemical behavior of MnV2O6-based materials and other transition metal oxides as electrodes for lithium storage.

Reconstruction of an underwater scattered image via incoherent modulation instability: erratum.

We correct an inaccurate description in the original paper [Opt. Lett.44, 695 (2019)OPLEDP0146-959210.1364/OL.44.000695].

Reconstruction of an underwater scattered image via incoherent modulation instability.

A technology of reconstructing a scattered image from turbid underwater is proposed, which is via stochastic resonance based on incoherent modulation instability in a noninstantaneous nonlinear medium. When intensity-dependent nonlinearity exceeds the threshold imposed by attenuation and scattering, instability preferentially reinforces the underlying signal modes at the expense of neighbor highly incoherent noise modes. Due to the directional energy transfer, noise-hidden signal images are effectively reconstructed with a cross-correlation gain high of 3.56. Results in turbid suspension demonstrated the wide applications of image detection in various dynamic scattering environments.

Convolutional Neural Network Based Synthesized View Quality Enhancement for 3D Video Coding.

The quality of synthesized view plays an important role in the three dimensional (3D) video system. In this paper, to further improve the coding efficiency, a convolutional neural network (CNN) based synthesized view quality enhancement method for 3D High Efficiency Video Coding (HEVC) is proposed. Firstly, the distortion elimination in synthesized view is formulated as an image restoration task with the aim to reconstruct the latent distortion free synthesized image. Secondly, the learned CNN models are incorporated into 3D HEVC codec to improve the view synthesis performance for both view synthesis optimization (VSO) and the final synthesized view, where the geometric and compression distortions are considered according to the specific characteristics of synthesized view. Thirdly, a new Lagrange multiplier in the rate-distortion (RD) cost function is derived to adapt the CNN based VSO process to embrace a better 3D video coding performance. Extensive experimental results show that the proposed scheme can efficiently eliminate the artifacts in the synthesized image, and reduce 25.9% and 11.7% bit rate in terms of peak-signal-to-noise ratio (PSNR) and structural similarity (SSIM) index, which significantly outperforms the state-of-theart methods.

Dynamic three-dimensional multifocal spots in high numerical-aperture objectives.

Multifocal spots in high numerical-aperture (NA) objectives has emerged as a rapid, parallel, and multi-location method in a multitude of applications. However, the typical method used for forming three-dimensional (3D) multifocal spots based on iterative algorithms limits the potential applications. We demonstrate a non-iterative method using annular subzone phases (ASPs) that are composed of many annular subareas in which phase-only distributions with different 3D displacements are filled. The dynamic 3D multifocal spots with controllable position of each focal spot in the focal volume of the objective are created using the ASPs. The experimental results of such dynamic tunable 3D multifocal spots offer the possibility of versatile process in laser 3D fabrication, optical trapping, and fast focusing scanned microscopic imaging.

[EFFECT OF DIFFERENT NECK-SHAFT ANGLE ON EFFICACY IN TREATMENT OF PROXIMAL HUMERAL FRACTURES WITH LOCKING PLATE].

OBJECTIVE: To observe the influence of different humeral neck-shaft angle on the efficacy in the treatment of proximal humeral fractures with locking plate. METHODS: A total of 106 patients with proximal humeral fractures were treated by locking plate between March 2009 and March 2013, and the clinical data were retrospectively analyzed. Of 106 cases, 58 were male and 48 were female, aged from 26 to 71 years (mean, 52.3 years). The causes were traffic accident injury in 54 cases, falling injury from height in 23 cases, falling injury in 21 cases, and others in 8 cases. According to the Neer classification, there were 32 cases of two-part fractures, 65 cases of three-part fractures, and 9 cases of four-part fractures. The time from injury to operation was 1-7 days (mean, 2.7 days). According to neck-shaft angle by X-ray measurements at 1-3 days after operation, the patients were divided into 3 groups: valgus group (> 145°), normal group (126-145°), and varus group (< 126°) to observe the influence of neck-shaft angle on efficacy. RESULTS: According to postoperative humeral neck-shaft angle, there were 10 cases in valgus group, 75 cases in normal group, and 21 cases in varus group. There was no significant difference in general clinical data among 3 groups (P > 0.05). The patients were followed up 6-12 months. The X-ray results showed fracture healing, and no significant difference was found in fracture healing time among 3 groups (P>0.05). After 6 months, the varus angle of femoral head and visual analogue scale (VAS) score of normal group were significantly lower than those of valgus group and varus group (P < 0.05). The excellent and good rate of Constant-Murley score was 78.67% (59/75) in normal group, and it was significantly higher than that in valgus group (60.00%, 6/10) and varus group (42.86%, 9/21) (P < 0.05), but there was no significant difference between valgus group and varus group (P > 0.05). The complication rate was 28.57% (6/21) in varus group, was 10.67% (8/75) in normal group, and was 20.00% (2/10) in valgus group, showing no significant difference among 3 groups (χ2 = 4.31, P = 0.12). CONCLUSION: Reconstruction of normal neck-shaft angle is the key to good shoulder function and clinical efficacy in the treatment of proximal humeral fracture.