Characterization of CD8+ T cells in immune-privileged organs of ZIKV-infected Ifnar1-/- mice.

Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E294-302-specific T cells can account for 20-60% of the total CD8+ T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E294-302-specific TCRαßs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αß paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8+ T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs.IMPORTANCEThe immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8+ T cells. Our data show that CD8+ T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/ß clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/ß clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5, was found to be selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8+ T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8+ T cells after ZIKV infection in different IPOs.

Parallel T Cell Immunogenic Regions in Influenza B and A Viruses with Distinct Nuclear Export Signal Functions: The Balance between Viral Life Cycle and Immune Escape.

Influenza A viruses (IAVs) and influenza B viruses (IBVs) cause annual epidemics in human populations with seasonal circulation spikes. Peptide AM58-66GL9 located at residues 58-66 of M1 protein of IAVs has been recognized as an immunodominant T cell epitope with HLA-A*0201 restriction and broadly used as a positive reference in influenza immunity. This peptide also almost completely overlaps with a nuclear export signal (NES) 59-68 in IAV M1, which explains the limited escape mutations under the T cell immune pressure in this region. In this study, we investigated the potential immunogenicity and NES in the corresponding region of IBV. The long peptide covering this region can be recognized by specific T cells and induce robust expression of IFN-γ among HLA-B*1501 donors in vivo, but not in HLA-A*0201 donors. Among a series of truncated peptides derived from this region, we identified an immunodominant HLA-B*1501-restricted T cell epitope BM58-66AF9 (ALIGASICF) in the M1 protein of IBV. Furthermore, the structure of the HLA-B*1501/BM58-66AF9 complex shows that BM58-66AF9 performs a flat and featureless conformation that is similar to AM58-66GL9 presented by HLA-A*0201. In contrast with IAV, the sequence around residues 55-70 of IBV M1 does not contain an NES. Our comparative study on IBVs and IAVs provides new insights into the immune and evolution characteristics of IBVs and may shed light on vaccine development for influenza viruses.

High Areal Capacity, Long Cycle Life Li-Air Batteries Enabled by Nano/Micro Hierarchical Porous Cathode.

The limited cycle life of Li-air batteries (LABs) with high areal capacity remains the chief challenge that hinders their practical applications. Here, the study proposes a hierarchical porous electrode (HPE) design strategy, in which porous MnO nanoflowers are built into mesopore/macropore electrodes through a combination of chemical dealloying and physical de-templating procedures. The MnO nanoflowers with 10-30 nm pore provides active sites to catalyze the O2 reduction and decomposition of discharged products. The 5-10 µm macroscopic pores in the cathode serve as channels of O2 transportation and facilitate the electrolyte permeation. The proposed HPE exhibits a full discharge capacity of 17.49 mAh cm-2 and stable cycle life >2000 h with a limited capacity of 6 mAh cm-2 . These results suggest that the HPE design strategy for LABs can simultaneously provide large capacity and robust cycle life, which is promising for advanced metal-air batteries.

Relationship of soil pH value and soil Pb bio-availability and Pb enrichment in tea leaves.

BACKGROUND: Lead (Pb) is not an essential element for the growth of tea trees, but it is an important index for evaluating the quality and safety of tea. Lead is a sensitive metal to pH. Exploring the changing trend of soil Pb and enrichment coefficient of Pb in tea leaves affected by soil acidification is significant for tea planting and tea quality safety control. RESULTS: A percent of 37.57% of the 364 tea plantations in Anxi county of China showed soil acidification that is a soil pH value < 4.5. However, the total Pb content in the soil and Pb content of tea leaves met the requirements stipulated in China. The soil available Pb content and Pb content in tea leaves were both significantly negatively correlated with soil pH value, and increased with the decrease of soil pH value. The soil available Pb content had a significant positive correlation with soil total Pb content. However, the soil total Pb content had no significant correlation with soil pH value. Moreover, the soil Pb bio-availability coefficient and the Pb enrichment coefficient of tea leaves decreased with the increase of soil pH value. CONCLUSION: More than a third of tea plantations in Anxi county had been acidified. The decrease of pH value leads to an increase in the bio-availability coefficient of soil Pb content and the enrichment coefficient of Pb content in tea leaves. The lower soil pH value resulted in the increase of the absorption and accumulation of Pb by tea trees, thus an increase of Pb content in tea leaves. © 2021 Society of Chemical Industry.

Strict Assembly Restriction of Peptides from Rabbit Hemorrhagic Disease Virus Presented by Rabbit Major Histocompatibility Complex Class I Molecule RLA-A1.

Rabbits are pivotal domestic animals for both the economy and as an animal model for human diseases. A large number of rabbits have been infected by rabbit hemorrhagic disease virus (RHDV) in natural and artificial pandemics in the past. Differences in presentation of antigenic peptides by polymorphic major histocompatibility complex (MHC) molecules to T-cell receptors (TCR) on T lymphocytes are associated with viral clearance in mammals. Here, we screened and identified a series of peptides derived from RHDV binding to the rabbit MHC class I molecule, RLA-A1. The small, hydrophobic B and F pockets of RLA-A1 capture a peptide motif analogous to that recognized by human class I molecule HLA-A*0201, with more restricted aliphatic anchors at P2 and PΩ positions. Moreover, the rabbit molecule is characterized by an uncommon residue combination of Gly53, Val55, and Glu56, making the 310 helix and the loop between the 310 and α1 helices closer to the α2 helix. A wider A pocket in RLA-A1 can induce a special conformation of the P1 anchor and may play a pivotal role in peptide assembly and TCR recognition. Our study broadens the knowledge of T-cell immunity in domestic animals and also provides useful insights for vaccine development to prevent infectious diseases in rabbits.IMPORTANCE We screened rabbit MHC class I RLA-A1-restricted peptides from the capsid protein VP60 of rabbit hemorrhagic disease virus (RHDV) and determined the structures of RLA-A1 complexed with three peptides, VP60-1, VP60-2, and VP60-10. From the structures, we found that the peptide binding motifs of RLA-A1 are extremely constraining. Thus, there is a generally restricted peptide selection for RLA-A1 compared to that for human HLA-A*0201. In addition, uncommon residues Gly53, Val55, and Glu56 of RLA-A1 are located between the 310 helix and α1 helix, which makes the steric position of the 310 helix in RLA-A1 much closer to the α2 helix than that found in other mammalian MHC class I molecules. This special conformation between the 310 helix and α1 helix plays a pivotal role in rabbit MHC class I assembly. Our results provide new insights into MHC class I molecule assembly and peptide presentation of domestic mammals. Furthermore, these data also broaden our knowledge on T-cell immunity in rabbits and may also provide useful information for vaccine development to prevent infectious diseases in rabbits.

Laser Direct Writing of Setaria Virids-Inspired Hierarchical Surface with TiO2 Coating for Anti-Sticking of Soft Tissue.

In minimally invasive surgery, the tendency for human tissue to adhere to the electrosurgical scalpel can complicate procedures and elevate the risk of medical accidents. Consequently, the development of an electrosurgical scalpel with an anti-sticking coating is critically important. Drawing inspiration from nature, we identified that the leaves of Setaria Virids exhibit exceptional non-stick properties. Utilizing this natural surface texture as a model, we designed and fabricated a specialized anti-sticking surface for electrosurgical scalpels. Employing nanosecond laser direct writing ablation technology, we created a micro-nano textured surface on the high-frequency electrosurgical scalpel that mimics the structure found on Setaria Virids leaves. Subsequently, a TiO2 coating was deposited onto the ablated scalpel surface via magnetron sputtering, followed by plasma-induced hydrophobic modification and treatment with octadecyltrichlorosilane (OTS) to enhance the surface's affinity for silicone oil, thereby constructing a self-lubricating and anti-sticking surface. The spreading behavior of deionized water, absolute ethanol, and dimethyl silicone oil on this textured surface is investigated to confirm the effectiveness of the self-lubrication mechanism. Furthermore, the sticking force and quality are compared between the anti-sticking electrosurgical scalpel and a standard high-frequency electrosurgical scalpel to demonstrate the efficacy of the nanosecond laser-ablated micro-nano texture in preventing sticking. The findings indicate that the self-lubricating anti-sticking surface fabricated using this texture exhibits superior anti-sticking properties.

The preparation of polysilicon films on highly boron doped silicon substrates and their effects on Cu out-diffusion.

The behavior of copper (Cu) diffusion at different storage temperatures of heavily boron-doped silicon substrates is investigated. The surface Cu concentration of the substrate with quantitative Cu contamination exhibits an initial increase followed by a subsequent decrease upon storage at 25 °C and 85 °C. The surface Cu, originating from the out-diffusion, can be effectively removed through RCA cleaning. The polysilicon film, prepared by low-pressure chemical vapor deposition (LPCVD) on the back of the substrate, exhibits a pronounced inhibitory effect on the out-diffusion of Cu. This phenomenon can be attributed to the effective gettering of Cu by both grain boundaries and disordered grain structures within the polycrystalline silicon film. Additionally, the multilayered structure of the polysilicon film exhibits enhanced gettering capabilities. The enhanced gettering effectiveness achieved by the multilayer polysilicon film can be attributed to an increased number of interfaces between layers.

Recent progress on the development of bioinspired surfaces with high aspect ratio microarray structures: From fabrication to applications.

Surfaces with high aspect ratio microarray structures can implement sophisticated assignment in typical fields including microfluidics, sensor, biomedicine, et al. via regulating their deformation or the material properties. Inspired by natural materials and systems, for example sea cockroaches, water spiders, cacti, lotus leaves, rice leaves, and cedar leaves, many researchers have focused on microneedle functional surface studies. When the surface with high aspect ratio microarray structures is stimulated by the external fields, such as optical, electric, thermal, magnetic, the high aspect ratio microarray structures can undergo hydrophilic and hydrophobic switching or shape change, which may be gifted the surfaces with the ability to perform complex task, including directional liquid/air transport, targeted drug delivery, microfluidic chip sensing. In this review, the fabrication principles of various surfaces with high aspect ratio microarray structures are classified and summarized. Mechanisms of liquid manipulation on hydrophilic/hydrophobic surfaces with high aspect ratio microarray structures are clarified based on Wenzel model, Cassie model, Laplace pressure theories and so on. Then the intelligent control strategies have been demonstrated. The applications in microfluidic, drug delivery, patch sensors have been discussed. Finally, current challenges and new insights of future prospects for dynamic manipulation of liquid/air based on biomimetic surface with high aspect ratio microarray structures are also addressed.

Potential diagnostic value of multiple indicators combined with total prostate-specific antigen in prostate cancer.

OBJECTIVE: We aimed to investigate the diagnostic value of different laboratory indicators in combination with total prostate-specific antigen (TPSA) for prostate cancer (PCa). METHODS: In this retrospective study, we selected 291 patients who underwent prostate biopsy. Patients were divided into the benign prostatic hyperplasia group and the PCa group. In both groups, patients were again divided into a group with TPSA 4.0-10.0 ng/mL and a group with TPSA >10.0 ng/mL. Clinical data including age, pre-puncture TPSA, free prostate-specific antigen (FPSA), and prostate volume (PV) were collected from all patients. We calculated the metrics PSA/PV (prostate-specific antigen density, PSAD), age/PV (AVR), age × PV/TPSA (PSA-AV), and (FPSA/TPSA)/PSAD [(F/T)/PSAD]). We plotted receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). RESULTS: We found statistically significant differences in PV, PSAD, AVR, PSA-AV, and (F/T) PSAD for patients with TPSA 4.0-10.0 ng/mL and TPSA >10 ng/mL. We further plotted the ROC of individual or combined indices in different subgroups and calculated the AUC. We found that the diagnostic efficacy of the combined indices was higher with TPSA >10 ng/mL. CONCLUSION: The combination of TPSA with multiple indicators may improve diagnostic accuracy for PCa.

Effect of continuous planting on Casuarina equisetifolia rhizosphere soil physicochemical indexes, microbial functional diversity and metabolites.

Continuous planting has a severe impact on the growth of Casuarina equisetifolia. In this study, the effects of three different long-term monocultures (one, two and three replanting) on the physicochemical indexes, microbial functional diversity, and soil metabolomics were analyzed in C. equisetifolia rhizosphere soil. The results showed that rhizosphere soil organic matter content, cation exchange capacity, total and available nitrogen, total and available phosphorus, and total and available potassium contents significantly decreased with the increasing number of continuous plantings. The evaluation of microbial functional diversity revealed a reduction in the number of soil microorganisms that rely on carbohydrates for carbon sources and an increase in soil microorganisms that used phenolic acid, carboxylic acid, fatty acid, and amines as carbon sources. Soil metabolomics analysis showed a significant decrease in soil carbohydrate content and a significant accumulation of autotoxic acid, amine, and lipid in the C. equisetifolia rhizosphere soil. Consequently, the growth of C. equisetifolia could hinder total nutrient content and their availability. Thus, valuable insights for managing the cultivation of C. equisetifolia and soil remediation were provided.

The CD8+ and CD4+ T Cell Immunogen Atlas of Zika Virus Reveals E, NS1 and NS4 Proteins as the Vaccine Targets.

Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2b) and BALB/c (H-2d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. In H-2b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. In contrast, in H-2d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2b and H-2d mice, respectively. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E294-302 and NS42351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2b and H-2d mice, respectively. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous ß2-Microglobulin.

The major histocompatibility complex (MHC) plays a pivotal role in antigen peptide presentation and T cell immune responses against infectious disease and tumor development. The hybrid MHC I complexed with heterologous ß2-microglobulin (ß2m) substitution from different species can be stabilized in vitro. This is a feasible means to study MHC I of mammals, when the homologous ß2m is not available. Meanwhile, it is indicated that mammalian ß2m substitution does not significantly affect peptide presentation. However, there is limited summarization regarding the methodology and the technology for the hybrid MHC I complexed with heterologous ß2-microglobulin (ß2m). Herein, methods to evaluate the feasibility of heterologous ß2m substitution in MHC I study are presented. These methods include preparation of expression constructs; purification of inclusion bodies and refolding of the MHC complex; determination of protein thermostability; crystal screening and structure determination. This study provides a recommendation for understanding function and structure of MHC I, and is also significant for T cell response evaluation during infectious disease and tumor immunotherapy.

Fine-root traits of allelopathic rice at the seedling stage and their relationship with allelopathic potential.

BACKGROUND: Allelopathic rice releases allelochemicals through its root systems, thereby exerting a negative effect on paddy weeds. This research aimed to evaluate the relationship between fine-root traits and the rice allelopathic potential at the seedling stage. METHODS: Two allelopathic rice cultivars, 'PI312777' and 'Taichung Native1,' and one non-allelopathic rice cultivar, 'Lemont,' were grown to the 3-6 leaf stage in a hydroponic system. Their fine roots were collected for morphological trait (root length, root surface area, root volume, and root tips number) in smaller diameter cutoffs and proliferative trait (root biomass) analysis. Their root-exudates were used for quantitative analysis of phenolic acids contents and an evaluation of allelopathic potential. Correlation analysis was also used to assess whether any linear relationships existed. RESULTS: Our results showed that allelopathic rice cultivars had significantly higher fine-root length having diameters <0.2 mm, more root tips number, and greater root biomass, coupled with higher allelopathic potential and phenolic acid contents of their root exudates, comparing with non-allelopathic rice cultivar. These fine-root traits were significantly-positively correlated to allelopathic inhibition and total phenolic contents in rice root-exudates. However, there were not significant correlations among the rice allelopathic potential and total phenolic acid contents of rice root-exudates with the root length, root surface area, and root volume of fine root in diameter >0.2 mm. DISCUSSION: Our results implied that fine-root traits appears to be important in understanding rice allelopathy at the seedling stage. The high allelopathic potential of rice cultivars might be attributed to their higher length of fine roots <0.2 mm in diameter and more number of root tips of fine root, which could accumulate and release more allelochemicals to solutions, thereby resulting in high inhibition on target plants. The mechanisms regulating this process need to be further studied.

Nonsphere Drop Impact Assembly of Graphene Oxide Liquid Crystals.

Creating long-lived topological textured liquid crystals (LCs) in confined nonspherical space is of significance in both generations of structures and fundamental studies of topological physics. However, it remains a great challenge due to the fluid character of LCs and the unstable tensional state of transient nonspheres. Here, we realize a rich series of topological textures confined in nonspherical geometries by drop impact assembly (DIA) of graphene oxide (GO) aqueous LCs. Various highly curved nonspherical morphologies of LCs were captured by gelator bath, generating distinct out-of-equilibrium yet long-lived macroscopic topological textures in 3D confinement. Our hydrodynamic investigations on DIA processes reveal that the shear-thinning fluid behavior of LCs and the arrested GO alignments mainly contribute to the topological richness in DIA. Utilizing the shaping behavior of GO LCs compared to other conventional linear polymers such as alginate, we further extend the DIA methodology to design more complex yet highly controllable functional composites and hybrids. This work thus reveals the potential to scale production of uniform yet anisotropic materials with rich topologic textures and tailored composition.