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Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial, and more studies are needed to understand their orchestration. In the present study, we characterize in depth and link pDC activation states in animals infected by mouse cytomegalovirus by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for how individual pDCs are endowed to exert different functions in vivo during a viral infection, in a manner tightly orchestrated in time and space.
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Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Infecções por Herpesviridae/imunologia , Muromegalovirus/fisiologia , Animais , Células Cultivadas , Interferon Tipo I/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Análise de Sequência de RNA , Transdução de Sinais , Análise de Célula Única , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. We found that two main transcriptionally distinct subsets of MBCs colonized the lung peribronchial niche after infection. These subsets arose from different progenitors and were both class switched, somatically mutated, and intrinsically biased in their differentiation fate toward plasma cells. Combined analysis of antigen specificity and B cell receptor repertoire segregated these subsets into "bona fide" virus-specific MBCs and "bystander" MBCs with no apparent specificity for eliciting viruses generated through an alternative permissive process. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.
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COVID-19 , Memória Imunológica , Animais , Linfócitos B , Pulmão , Células B de Memória , Camundongos , Reinfecção , SARS-CoV-2RESUMO
BACKGROUND: Hematoma expansion is an independent predictor of patient outcome and mortality. The early diagnosis of hematoma expansion is crucial for selecting clinical treatment options. This study aims to explore the value of a deep learning algorithm for the prediction of hematoma expansion from non-contrast computed tomography (NCCT) scan through external validation. METHODS: 102 NCCT images of hypertensive intracerebral hemorrhage (HICH) patients diagnosed in our hospital were retrospectively reviewed. The initial computed tomography (CT) scan images were evaluated by a commercial Artificial Intelligence (AI) software using deep learning algorithm and radiologists respectively to predict hematoma expansion and the corresponding sensitivity, specificity and accuracy of the two groups were calculated and compared. Comparisons were also conducted among gold standard hematoma expansion diagnosis time, AI software diagnosis time and doctors' reading time. RESULTS: Among 102 HICH patients, the sensitivity, specificity, and accuracy of hematoma expansion prediction in the AI group were higher than those in the doctor group(80.0% vs 66.7%, 73.6% vs 58.3%, 75.5% vs 60.8%), with statistically significant difference (p < 0.05). The AI diagnosis time (2.8 ± 0.3 s) and the doctors' diagnosis time (11.7 ± 0.3 s) were both significantly shorter than the gold standard diagnosis time (14.5 ± 8.8 h) (p < 0.05), AI diagnosis time was significantly shorter than that of doctors (p < 0.05). CONCLUSIONS: Deep learning algorithm could effectively predict hematoma expansion at an early stage from the initial CT scan images of HICH patients after onset with high sensitivity and specificity and greatly shortened diagnosis time, which provides a new, accurate, easy-to-use and fast method for the early prediction of hematoma expansion.
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Hemorragia Cerebral , Aprendizado Profundo , Inteligência Artificial , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND & AIMS: In most autoimmune disorders, crosstalk of B cells and CD4 T cells results in the accumulation of autoantibodies. In autoimmune hepatitis (AIH), the presence of anti-soluble liver antigen (SLA) autoantibodies is associated with reduced overall survival, but the associated autoreactive CD4 T cells have not yet been characterised. Herein, we isolated and deeply characterised SLA-specific CD4 T cells in patients with AIH. METHODS: We used brief ex vivo restimulation with overlapping SLA peptides to isolate and phenotype circulating SLA-specific CD4 T cells, and integrative single-cell RNA-seq (scRNA-seq) to characterise their transcriptome and T-cell receptor (TCR) repertoire. Autoreactive TCRs were cloned and used to identify dominant SLA-derived epitopes. SLA-specific CD4 T cells were tracked in peripheral blood through TCR sequencing to identify their phenotypic niche. We further characterised disease-associated peripheral blood T cells by high-content flow cytometry in 42 patients with AIH and 17 controls with non-alcoholic steatohepatitis. RESULTS: Autoreactive SLA-specific CD4 T cells were only detected in patients with anti-SLA autoantibodies and had a memory PD-1+CXCR5-CCR6-CD27+ phenotype. ScRNA-seq revealed their pro-inflammatory/B-helper profile. SLA81-100 and SLA177-204 contain dominant T-cell epitopes. Autoreactive TCR clonotypes were predominantly found in the memory PD-1+CXCR5-CD4 T cells, which were significantly increased in the blood of patients with AIH and supported B-cell differentiation through IL-21. Finally, we identified specific T-cell phenotypes linked to disease activity and IgG level during AIH. CONCLUSIONS: We provide a deep characterisation of rare circulating autoreactive CD4 T cells and identify their peripheral reservoir in AIH. We also propose a specific phenotype of autoreactive T cells related to AIH disease activity, which will be essential to track, delineate, and potentially target these pathogenic cells. LAY SUMMARY: One principal characteristic of autoimmune hepatitis (AIH), like for many other autoimmune diseases, is the accumulation of autoantibodies produced by B lymphocytes following their interaction with autoreactive CD4 T lymphocytes. In this study, we identified and characterised with high resolution these CD4 T cells. This will be essential to track, delineate, and potentially target them during AIH.
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Autoantígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Hepatite Autoimune , Adulto , Autoanticorpos/imunologia , Linfócitos B/imunologia , Epitopos de Linfócito T/análise , Feminino , Hepatite Autoimune/sangue , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores CXCR5/genética , Análise de Sequência de RNA , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genéticaRESUMO
The present paper attempts to identify the molecule-like structural units in inorganic compounds, by applying the so-called "cluster plus glue atom model". This model, originating from metallic glasses and quasi-crystals, describes any structure in terms of a nearest-neighbor cluster and a few outer-shell glue atoms, expressed in the cluster formula [cluster](glue atoms). Similar to the case for normal molecules where the charge transfer occurs within the molecule to meet the commonly known octet electron rule, the octet state is reached after matching the nearest-neighbor cluster with certain outer-shell glue atoms. These kinds of structural units contain information on local atomic configuration, chemical composition, and electron numbers, just as for normal molecules. It is shown that the formulas of typical inorganic compounds, such as fluorides, oxides, and nitrides, satisfy a similar octet electron rule, with the total number of valence electrons per unit formula being multiples of eight.
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High-performance conventional engineering materials (including Al alloys, Mg alloys, Cu alloys, stainless steels, Ni superalloys, etc.) and newly-developed high entropy alloys are all compositionally-complex alloys (CCAs). In these CCA systems, the second-phase particles are generally precipitated in their solid-solution matrix, in which the precipitates are diverse and can result in different strengthening effects. The present work aims at generalizing the precipitation behavior and precipitation strengthening in CCAs comprehensively. First of all, the morphology evolution of second-phase particles and precipitation strengthening mechanisms are introduced. Then, the precipitation behaviors in diverse CCA systems are illustrated, especially the coherent precipitation. The relationship between the particle morphology and strengthening effectiveness is discussed. It is addressed that the challenge in the future is to design the stable coherent microstructure in different solid-solution matrices, which will be the most effective approach for the enhancement of alloy strength.
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This study combined rice starch (RS) with cactus polysaccharide (CP) at different composites (0.6%, 1.2%, 1.8%, 2.4%, and 3.0%, w/w), and analyzed the variations in the complex gelatinization properties, rheological properties, thermal properties, structural properties, digestibility, and freeze-thaw stability. As a result, the pasting parameters (p < 0.05) and storage modulus (G') together with the loss modulus (Gâ³) decreased as the CP concentration increased; meanwhile, the RS and the CP-RS gels were pseudoplastic fluids. As revealed by differential scanning calorimetry (DSC), incorporating CP into the starch elevated the starch gelatinization temperature while decreasing gelatinization enthalpy, revealing that CP effectively retarded long-term retrogradation in RS. The gel microstructure and crystallization type altered after adding CP. Typically, CP inclusion could enhance the proportion of resistant starch and slowly digestible starch (SDS), thereby slowing RS hydrolysis. Concurrently, adding CP promoted the RS freeze-thaw stability. These findings could potentially aid in the innovation of CP-based food products.
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In this study, for the first time, a cluster-plus-glue-atom model was used to optimize the composition of lithium aluminosilicate glass-ceramics. Basic glass in glass-ceramics was considered to be a 16-unit combination of three-valence {M2O3} and one-valence {Li2O} units. By adjusting the ratio of {M2O3} and {Li2O}, the composition of basic glass could be optimized. After optimization, the average cation valence of the base glass was increased to 2.875. After heat treatment of the optimized base glass, it is found that the crystal size, proportion, and crystallinity changed obviously compared with that before optimization. The main crystalline phases of all the lithium aluminosilicate glass-ceramics prepared in this work were Li2Si2O5 and LiAlSi4O10. All optimized glass-ceramics had an obvious improvement in the crystallinity, with one of the largest having a crystallinity of over 90%. Furthermore, its bending strength was 159 MPa, the microhardness was 967 Hv, and the visible light transmission rate exceeded 90%. Compared with the widely used touch panel cover glass, the optical properties were close, and the mechanical properties were greatly improved. Due to its excellent performance, it could be used in microelectronics, aerospace, deep-sea exploration, and other fields.
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Correction for 'One-step mild preparation of tough and thermo-reversible poly(vinyl alcohol) hydrogels induced by small molecules' by Chuang Dong et al., Chem. Commun., 2021, 57, 3789-3792, https://doi.org/10.1039/D1CC00578B.
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Background: Background parenchymal enhancement (BPE) is defined as the enhanced proportion of normal fibroglandular tissue on enhanced magnetic resonance imaging. BPE shows promise as a quantitative imaging biomarker (QIB). However, the lack of consensus among radiologists in their semi-quantitative grading of BPE limits its clinical utility. Methods: The main objective of this study was to develop a BPE quantification model according to clinical expertise, with the BPE integral being used as a QIB to incorporate both the volume and intensity of the enhancement metrics. The model was applied to 2,786 cases to compare our quantitative results with radiologists' semi-quantitative BPE grading to evaluate the effectiveness of using the BPE integral as a QIB for analyzing BPE. Comparisons between multiple groups of nonnormally distributed BPE integrals were performed using the Kruskal-Wallis test. Results: Our study found a considerable degree of concordance between our BPE quantitative integral and radiologists' semi-quantitative assessments. Specifically, our research results revealed significant variability in BPE integral attained through the BPE quantification framework among all semi-quantitative BPE grading groups labeled by experienced radiologists, including mild-moderate (P<0.001), mild-marked (P<0.001), and moderate-marked (P<0.001). Furthermore, there was an apparent correlation between BPE integral and BPE grades, with marked BPE displaying the highest BPE integral, followed by moderate BPE, with mild BPE exhibiting the lowest BPE integral value. Conclusions: The study developed and implemented a BPE quantification framework, which incorporated both the volume and intensity of enhancement and which could serve as a QIB for BPE.
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Phycobilisomes are light-harvesting supramolecular complexes in cyanobacteria and red algae. Linkers play a pivotal role in the assembly and energy transfer modulation of phycobilisomes. However, how linkers function remains unclear due to the lack of structural and biochemical studies of linkers, especially the N-terminal domain of L(R) (pfam00427). Here, we report the crystal structure of the pfam00427 domain of the linker L(R) (30) from Synechocystis sp. PCC 6803 at 1.9 Å. The pfam00427 presents as a previously uncharacterized point symmetric six α-helix bundle. To elucidate the binding style of pfam00427 in the C-phycocyanin (C-PC) (αß)(6) hexamer, we fixed pfam00427 computationally into the C-PC (αß)(6) inner cavity using the program AutoDock. Combined with a conserved 'C-PC binding patch' on pfam00427 identified, we arrived at a model for the pfam00427-C-PC (αß)(6) complex. This model was further optimized and evaluated as a reasonable result by a molecular dynamics simulation. In the resulting model, the pfam00427 domain is stably positioned in the central hole of the C-PC trimer. Moreover, the L(RT) (pfam01383) was docked into our pfam00427-C-PC model to generate a complete phycobilisome rod in which the linkers join individual biliprotein hexamers.
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Ficobilissomas/metabolismo , Ficocianina/química , Ficocianina/metabolismo , Multimerização Proteica , Synechocystis/química , Synechocystis/metabolismo , Cristalografia por Raios X , Modelos Moleculares , Simulação de Dinâmica MolecularRESUMO
During the last several decades, since the discovery of a decagonal quasicrystal, a 2 nm cluster model has been widely accepted as its basic quasi-unit-cell (QUC). Instead of the traditional 2 nm QUC, a 3.2 nm QUC is proposed in this paper. The 3.2 nm QUC can fill all the blank areas. The 3.2 nm QUC consists of 251 atoms. The element type and position of each atom are determined using high-angle annular detector dark-field (HAADF) images taken along three projection directions, i.e., one along the ten-fold symmetry and the other two along the two-fold symmetry with an intersection angle of 18 degrees. The proposed model opens an avenue for further investigation of the aperiodic atomic structure of other quasicrystals.
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Carbon fiber fabric-reinforced phenolic resin composites are widely used as thermal protection materials for thermal protection systems in hypersonic vehicles and capsules. In this work, carbon fiber fabric-reinforced boron phenolic resin composites modified with MoSi2 and B4C were prepared via a compression molding technique. The high-temperature performance of the composites as well as the oxidation behavior of the carbon fibers was studied. The results indicate that the incorporation of B4C improves the performance of composites at high temperatures. The residual weight rate of composites with 15 phr B4C (BP-15) sufficiently increased from 23.03% to 32.91% compared with the composites without B4C (BP-0). After being treated at 1400 °C for 15 min, the flexural strength of BP-15 increased by 17.79% compared with BP-0. Compared with BP-0, the line ablation rate and mass ablation rate of BP-15 were reduced by 53.96% and 1.56%, respectively. In addition, MoSi2 and B4C particles had a positive effect on the oxidation of carbon fibers in the composites. After treatment at 1400 °C, the diameter of the as-received carbon fiber was reduced by 31.68%, while the diameter of the carbon fiber in BP-0 and BP-15 decreased by 15.12% and 6.14%, respectively. At high temperatures, the liquid B2O3 from B4C and MoSi2-derived complex-phase ceramics (MoB, MoB2, Mo2C, Mo4.8Si3C0.6) acted as an oxygen barrier, effectively mitigating the oxidation degree of the carbon fibers.
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Rapid and accurate detection of fluoroquinolones (FQs) antibiotics residues in food substrate are of great significance to food safety. In this study, terahertz spectroscopy was employed to conduct the spectral and imaging analysis to explore its feasibility for detection concentrations of FQs in fish meal feeds (FMF). Four methods (frequency of maximum difference in frequency-domain, characteristic absorption peak, successive projections algorithm and stepwise regression) were used to selected characteristic frequencies of sample. Terahertz imaging was formed at selected characteristic frequency and back propagation neural network was used to establish quantitative evaluation models to select optimal characteristic imaging frequency. Finally, relationship between concentrations of FQs and their gray values was revealed, and each data had a small range of error bar. The results showed that terahertz spectral and imaging technique can visualize norfloxacin and enrofloxacin concentrations in FMF precisely. This study explored a brand-new visualization method for quantitative detection of FQs in FMF based on terahertz spectral and imaging technology.
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Fluoroquinolonas , Norfloxacino , Antibacterianos , Enrofloxacina , TecnologiaRESUMO
Solid solutions are the basis for most industrial alloys. However, the relationships between their characteristic short-range orders and chemical compositions have not been established. The present work combines Cowley parameter α with our cluster-plus-glue-atom model to accurately derive the chemical units of binary solid-solution alloys of face-centered cubic type. The chemical unit carries information on atomic structure and chemical composition, which explains prevailing industrial alloys. For example, chemical units in Cu68.9Zn31.1 alloy with α1 = - 0.137 are formulated as [Zn-Cu10Zn2]Zn2Cu2 and [Zn-Cu10Zn2]Zn3Cu1, with 64.0-70.0 wt% Cu corresponding to the most widely used cartridge brass C26000 (68.5-71.5 Cu). This work answers the long-standing question on the composition origin of solid-solution-based industrial alloys, by tracing to the molecule-like chemical units implied in chemical short-range ordering in solid solutions.
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Soft magnetic high-entropy alloy thin films (HEATFs) exhibit remarkable freedom of material-structure design and physical-property tailoring, as well as, high cut-off frequencies and outstanding electrical resistivities, making them potential candidates for high-frequency magnetic devices. In this study, a CoCrFeNi film with excellent soft magnetic properties is developed by forming a novel core-shell structure via native oxidation, with ferromagnetic elements Fe, Co, and Ni as the core and the Cr oxide as the shell layer. The core-shell structure enables a high saturation magnetization, enhances the electrical resistivity, and thus reduces the eddy-current loss. For further optimizing the soft magnetic properties, O is deliberately introduced into the HEATFs, and the O-incorporated HEATFs exhibit an electrical resistivity of 237 µΩ·cm, a saturation magnetization of 535 emu cm-3 , and a coercivity of 23 A m-1 . The factors that determine the ferromagnetism and coercivity of the CoCrFeNi-based HEATFs are examined in detail by evaluating the microstructures, magnetic domains, chemical valency, and 3D microscopic compositional distributions of the prepared films. These results are anticipated to provide insights into the magnetic behaviors of soft magnetic HEATFs, as well as aid in the construction of a promising material-design strategy for these unique materials.
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The phase-type of a stainless steel is generally predicted by equivalent equations in terms of a major austenitic (γ) or ferritic (α) stabilizer Ni or Cr. The present paper attempts to understand the equivalent methods in stainless steels via the slopes of the phase boundary lines separating γ and γ + α phase zones. The prevailing equivalent coefficients are well interpreted using the slope ratios of the alloying elements divided by that of Ni or Cr, after analyzing over one hundred common stainless steels. Different from traditional composition equivalents which evaluate γ stabilizers and α stabilizers separately; the new equivalent scheme provides a unified phase stabilizing parameter for all alloying elements in stainless steels. This parameter is defined as γ stabilizing efficiency. Its negative or positive sign indicates γ stabilizer or α stabilizer, and its value represents the stabilizing efficiency.
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This paper focuses on the revelation of structural relationship of the ordered and disordered states in Cu-(Zr, Ti) binary systems. The atomic radial distributions in real space and the electron scattering behavior in reciprocal space between crystalline and amorphous phases are compared. The spherical-periodic order, characteristic of disordered structures, is clearly present in the crystalline phases, suggesting the structural homology of crystalline and the corresponding amorphous states. Furthermore, the diameters of Brillouin- or Jones-zones at the Fermi level in the crystalline and amorphous states are also similar and they fall close to those of the calculated Fermi spheres, verifying the resonance between the static atomic structure and the electron wave.
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Reaching simultaneously high mechanical strength and low electrical resistivity is difficult as both properties are based on similar microstructural mechanisms. In our previous work, a new parameter, the tensile strength-over-electrical resistivity ratio, is proposed to evaluate the matching of the two properties in Cu alloys. A specific ratio of 310 × 108 MPa·Ω-1·m-1, independent of the alloy system and thermal history, is obtained from Cu-Ni-Mo alloys, which actually points to the lower limit of prevailing Cu alloys possessing high strength and low resistivity. The present paper explores the origin of this specific ratio by introducing the dual-phase mechanical model of composite materials, assuming that the precipitate particles are mechanically mixed in the Cu solid solution matrix. The strength and resistivity of an alloy are respectively in series and parallel connections to those of the matrix and the precipitate. After ideally matching the contributions from the matrix and the precipitate, the alloy should at least reach half of the resistivity of pure Cu, i.e., 50%IACS, which is the lower limit for industrially accepted highly conductive Cu alloys. Under this condition, the specific 310 ratio is related to the precipitate-over-matrix ratios for strength and resistivity, which are both two times those of pure Cu.
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We suggest a simple idea of bio-based adhesives with strong adhesion even under water. The adhesives simply prepared via polycondensation of 3,4-dihydroxyhydrocinnamic acid (DHHCA) and lactic acid (LA) in one pot polymerization. Poly(DHHCA-co-LA) has a hyperbranched structure and demonstrated strong dry and wet adhesion strength on diverse material surfaces. We found that their adhesion strength depended on the concentration of DHHCA. Poly(DHHCA-co-LA) with the lowest concentration of DHHCA showed the highest adhesion strength in water with a value of 2.7 MPa between glasses, while with the highest concentration of DHHCA it exhibited the highest dry adhesion strength with a value of 3.5 MPa, which was comparable to commercial instant super glue. Compared to underwater glues reported previously, our adhesives were able to spread rapidly under water with a low viscosity and worked strongly. Poly(DHHCA-co-LA) also showed long-term stability and kept wet adhesion strength of 2.2 MPa after steeping in water for 1 month at room temperature (initial strength was 2.4 MPa). In this paper, Poly(DHHCA-co-LA) with strong dry and wet adhesion properties and long-term stability was demonstrated for various kinds of applications, especially for wet conditions.