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Introducing the isocyanate group on the carbon fibre (CF) to improve surface activity is an effective modification method. Still, its application in the industrial field is restricted because the modification process is harmful to the environment and isocyanate is easy to fail. In this paper, 3-isocyanopropyltriethoxysilane (IPTS) has been blocked with caprolactam (CPL) have been prepared. By adjusting the hydrolysis conditions and concentration of the modified coupling agent solution, the CPL-blocked IPTS was grafted to the surface oxidized CF, and the CF-reinforced polyamide 6 (PA6) composites were prepared. After treating CF with 1.0wt% coupling agent solution, the composites’ interlaminar shear strength (ILSS) reached 52.53 MPa, which was 23.83% greater than that of the desized CF/PA6 composites. High-temperature composite molding caused CPL-blocked IPTS to unblock, and the isocyanate that was released thermally intereacted with the terminal amino group of PA6 to establish a high strength interface through covalent grafting, which was the main reason for improving ILSS. This study indicates that this method is safe and simple and can effectively improve the interface properties of CF/PA6 composites.

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the Her2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR T cells.Graphical abstractUniversal CAR T cells based on Fcγ receptors exhibit a specific tumor-killing effect. However, the affinities of Fcγ receptors greatly influence the efficacy and adverse effectsin vivo.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium–GPX4–ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination. T follicular helper (TFH) cells are important for the generation of effective antibody responses. Yu and colleagues find that TFH cells are exceptionally sensitive to death by ferroptosis and that this process is regulated by the activity of the selenoenzyme GPX4.

Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3–106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral–host interaction and the disease pathogenesis.

Epoxy and epoxide composites have a wide range of outdoor applications wherein they are affected by ageing. In this study, epoxy casting plates and epoxy-based composite rods for use in overhead conductors were prepared. A concurrent investigation concerning the ageing of epoxy resins and their carbon fibre composites was carried out via artificially accelerated experiments under hygrothermal and salt mist conditions. The moisture penetration along the depth, water absorption, appearance, hardness, density of the epoxy resins, and variation patterns of the impact strength and tensile strength of the epoxy-based composites were investigated. The ageing mechanisms were explored using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Both ageing modes had essentially similar influences on the properties of the resins and their composites; moreover, they did not significantly affect the chemical structure and microstructure of the epoxy resin, with the physical adsorption of water primarily observed during the ageing process. The moisture absorption behaviour of the epoxy obeyed Fick’s law. Although the water penetration rate in the salt mist ageing mode was slightly higher than that in the hygrothermal ageing mode during the early ageing stage, it was essentially the same during the later stage. The final moisture absorption rate at saturation was approximately 1.1% under both modes. The flexural strengths and impact strengths of the composites in both ageing modes followed a similar trend. They decreased gradually with the ageing time and then stabilized at almost the same value. The flexural strength was reduced from 803 MPa to 760 MPa and the impact strength from 383 J/m2 to 310 J/m2, indicating a decrease of approximately 5.4% and 19%, respectively. The absorbed water during the ageing process caused micro-cracks at the interface between the fibres and resin, weakening the interfacial strength and reducing the mechanical properties of the composites.

Introduction Dragendorff's reagent has low sensitivity and non-specificity for some alkaloids. A new alkaloid derivatisation reagent has been developed and optimised by using a Box-Behnken design method. This new reagent is applicable for structurally diverse natural alkaloids, and is proposed as a universal alkaloid staining reagent. Objective To establish an efficient and sensitive thin-layer chromatography (TLC) identification method for Leonuri Herba and Leonuri Fructus to characterise their differences and similarities. Method Three key components (bismuth subnitrate, potassium iodide and iodine) in the derivatisation reaction were re-constructed and optimised using a response surface method. Different inorganic acids, essential additives of the staining reaction, were compared by a single-factor experiment design. Results This newly optimised reagent for alkaloids reported in this study, named the enhanced Dragendorff-Wagner's reagent, is composed of 0.82% bismuth subnitrate, 11.1% potassium iodide and 0.76% iodine in 38% phosphoric acid solution. Validation results indicate that the TLC spot of stachydrine stained with the enhanced Dragendorff-Wagner's reagent had a limit of detection of 2.0 μg, good intra- and inter-plate, and intra- and intra-day precisions with relative standard devition values less than 5.0%, and stability over 90 min. Conclusion This enhanced Dragendorff-Wagner's reagent was applied for TLC identification of 16 reference alkaloids representing 11 structural skeletons, and two closely related herbs (Leonuri Herba and Leonuri Fructus). This newly enhanced Dragendorff-Wagner's reagent is a universal, effective, and sensitive staining reagent for alkaloids.

Sodium-ion batteries (SIBs) are one of the most potential candidates for large-scale energy storage due to the low cost and eco-friendliness, however, a stable and reversible anode is urgently developed. In this work, a novel 2 × 2 tunnel-structured K1.28Ti8O16@N-doped carbon nanofibers (KTO@N CNFs) anode is successfully synthesized via simple electrospinning and subsequent thermal treatment with urea acted as the additional convenient nitrogen source. In-situ X-ray diffraction (XRD) measurement confirms the intercalation reaction mechanism and robust structure during Na+insertion/extraction. This composite material exhibits a reversible capacity of 116.4 mAh g − 1 at a current density of 100 mA g − 1 after 1000 cycles. More impressively, even at a high current density of 1 A g − 1, the battery delivers capacity retention of 98.4 mAh g − 1 after 5000 cycles. The excellent electrochemical performance is attributed to the adequate 2 × 2 tunnel structure and the nano-confinement of N-doped nanofibers on K1.28Ti8O16 nanocrystals, which offers enough diffusion paths and enhance the ionic diffusion of sodium ions. This work provides a facile strategy to synthesis stable, reversible, and long-cycle anode for sodium-ion batteries.

Sodium- and potassium-ion batteries (SIBs and PIBs), as the next-generation batteries, attract a lot of attention due to the abundance and even distribution of sodium and potassium sources. However, both SIBs and PIBs need high-performing active anode materials to widen their industrial applications. Transition metal sulfides, possessing high theoretical capacity, show promise for SIB and PIB anodes. However, the structural instability of these sulfides occurring due to the volume changes during the active ion insertion and release limits their applications. In this work, V5S8 nanoparticles anchored on carbon nanofibers (V5S8@CNF) were fabricated for SIB and PIB anodes. The SIB cells exhibited outstanding performance with 351.0 mA h g-1 specific capacity after 400 cycles at 0.2 A g-1. A similar PIB cell demonstrated 289.2 mA h g−1 specific capacity after 200 cycles at 0.1 A g−1. Long-term stability of SIBs and PIBs for 10000 and 2000 cycles at 2 and 1 A g−1, respectively, showed very stable specific capacities equal to 251.0 and 190.1 mA h g−1. The outstanding energy-storage-related properties of the sulfide-based anodes provide insights into techniques for improving Na+ and K+ electrochemical reactions assisted by two-dimensional layered transition metal sulfides.

In the originally published version of this Article, there was an error in Extended Data Fig. 10c. Specifically, in Extended Data Fig. 10c, third panel to the right, the y-axis label (In CD4+ cells (%)) was incorrect. The correct label has been amended to read: “In CD4+ CXCR5+cells (%).” The change has been made to the online version of the Article.

It is one of the main forms of multi-aircraft cooperative air combat to attack targets by cooperative tactics. In this paper, aiming at the problem of threat assessment for rotte of enemy in over-the-horizon air combat, a method of threat assessment based on cooperative tactical recognition is proposed. Firstly, based on the analysis of the cooperative tactics of rotte in air combat and the division of functions between target leader and wingman, a model of cooperative tactical recognition is established by using dynamic Bayesian network. Then, according to the information of flight status and maneuver recognition results, the prediction of target trajectory is made. Finally, the comprehensive model of threat assessment is established by considering such threat factors as detection effectiveness, attack effectiveness, cooperative tactical and situation evolution. The simulation results show that the method can accurately identify the cooperative tactics of the rotte and achieve reasonable threat assessment of target leader and wingman.

For this study, lithium-ion pouch cells undergo quasi-static and dynamic tests and are analyzed by interdisciplinary characterization methods. These methods reveal different behaviors of the cells under mechanical-electrochemical coupled failure. The study demonstrates that the inertia effect of a cell's multilayer structure dominates the failure under dynamic loading rather than the strain rate effect of the cell's components. This finding unlocks the underlying mechanism of localized fractures near the impacted surface and counterintuitive premature failures with less critical force under dynamic loading conditions. In addition to instant failure with inflection points in force/voltage curves, this study observes an interesting delayed failure behavior without evident short-term signs in both dynamic and quasi-static tests with different mechanisms. This challenges the validity of using macroscopic inflection points in mechanical tests as indicators for failure prediction and could explain the postponed spontaneous combustion of a cell after mechanical abuse accidents. The cell's capacity and internal resistance after dynamic and quasi-static tests are also assessed. Finally, an experimental evaluation outline is proposed for lithium-ion cells under mechanical abuse. This work sheds light on the understanding of dynamic failure mechanisms and safety evaluation methods for lithium-ion cells.

Although quasi-static responses of lithium-ion batteries has been studied by many researchers recently, the dynamic behaviors and its underlying mechanism under crushing are still not fully understood. In this paper, the stress wave theory is employed to analyze the dynamic behaviors of 18,650 lithium-ion batteries for the first time. A numerical model of the battery cell is established and validated by experiments, which is then used to study the dynamic response under crushing within a wide scope of crushing velocity (up to 45 m/s). Many different responses are found that differ from quasi-static cases, including the early short circuit before drop in force, the “rise-drop-plateau-rise” force-displacement curve, the velocity-dependent crack positions and so on, all of which can be well characterized by stress wave. It is interesting that the failure displacement and the short-circuit position of the battery depends on the range of crushing velocity, which is resulted from different dynamic failure mechanism in each velocity range. Accordingly, a velocity-dependent failure criterion is obtained. The results show that a more specific strategy is needed in the safety design of battery modules under various crushing velocities.

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.

SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid cells and CD4+ T cells, while Vpx can mediate SAMHD1 degradation to promote HIV-1 replication. Although the restriction mechanisms of SAMHD1 have been well-described, SAMHD1 expression and Vpx-mediated SAMHD1 degradation during chronic HIV-1 infection were poorly understood. Flow cytometric analysis was used to directly visualize ex vivo, and after in vitro SIV-Vpx treatment, SAMHD1 expression in CD4+ T cells and monocytes. Here we report activated CD4+ T cells without SAMHD1 expression were severely reduced, and SAMHD1 in CD4+ T cells became susceptible to SIV-Vpx mediated degradation during chronic HIV-1 infection, which was absent from uninfected donors. These alterations were irreversible, even after long-term fully suppressive antiretroviral treatment. Although SAMHD1 expression in CD4+ T cells and monocytes was not found to correlate with plasma viral load, Vpx-mediated SAMHD1 degradation was associated with indicators of immune activation. In vitro assays further revealed that T-cell activation and an upregulated IFN-I pathway contributed to these altered SAMHD1 properties. These findings provide insight into how immune activation during HIV-1 infection leads to irreparable aberrations in restriction factors and in subsequent viral evasion from host antiviral defenses.

Recombination contributes substantially to the genetic diversity of HIV-1, and is likely to occur in populations in which multiple subtypes circulate. Molecular epidemiological studies showed that subtype B, CRF01_AE, and CRF07_BC are currently circulating in parallel among men who have sex with men (MSM) in China, suggesting the possible emergence of new recombinants. In the present study, we identified two new HIV Type 1 unique (CRF01_AE /B) recombinant forms in this population by near full-length genomic analysis. Our data provided the first description of the near full-length genomes of these new CRF01_AE/B recombinants as well as important insights into the complexity of HIV-1 recombinant strains currently in circulation among MSM in China. These data highlight the importance of continuous surveillance of the dynamic change of HIV-1 subtypes and new recombinants among the MSM population.

Secondary precipitation takes place in alloy 7050 during slow quenching after solution and results in a significantly decreased content of Mg, Zn elements. Optical microscopy, transmission electron microscopy (TEM), and electron backscatter diffraction (EBSD) study showed the distribution of Al 3 Zr particles plays a vital role in quenching process. The equilibrium η phases mainly precipitate at Al 3 Zr particles within the recrystallized grains and other high energy areas (primarily grain boundaries). The influence of the processing (homogenization, hot rolling and solution) parameter on the quench sensitivity is also investigated by mechanical property examination (T6 temper). A ramping heat homogenization, controlled hot rolling (67% rolling reduction and 3–5 s −1 deformation rate) and two-stage solution treatment result in lesser recrystallization and fewer high angle grain boundaries, and lower the boundary angles within sub-structures. The decreasing number of heterogeneous precipitation sites endows the study alloy with good quenching sensitivity and better mechanical properties.

The aim of this study was to test whether deglycosylation of an HIV-1 AE recombinant-derived gp140 could enhance the induction of neutralizing antibodies. N-to-Q mutations were introduced in the V1/V2 (m157/161) or V4 (m382/388) loops by using overlapping PCR. BALB/c mice were inoculated with different DNA vaccines at weeks 0, 2, 4, and 7. The Elispot assay was used to quantify Env-specific T-cell immunity, and the TZM-bl cell-based in vitro neutralizing assay with primary isolates was used to assess humoral immune responses. Our data showed that two mutant DNA vaccines, designated m157/161 and m382/388, mounted total T-cell responses that were at levels similar those of the unmutated vaccine. Although the levels of binding antibodies elicited by the two mutants were significantly lower than the levels elicited by the unmutated vaccine, cross-reactive neutralizing antibodies were observed only in the sera that received the mutant DNA vaccines. These data demonstrate that deglycosylation of HIV-1 Env could enhance the capacity to elicit cross-reactive neutralizing antibodies.

The effect of temperature and environment (air, humidity and 3.5 wt% NaCl salt spray) on cyclic fatigue life and fracture mechanism on 2524 aluminum alloy was investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and fatiguae property testing. The results showed that temperature has a detrimental influence on cyclic fatigue life. The cyclic fatigue strength n=106 at elevated temperature (100%°C) decreased by 30 MPa compared to that at cryogenic temperature (-55°C). Moreover, temperature also remarkably affected the feature of dislocation, second-phase particles and grain boundary. The fracture surface at cryogenic temperature showed crystallographic morphology. The dominant deformation process at ambient and elevated temperature was a combination of predominantly transgranular and local intercrystalline fracture mechanism. The fractographic features revealed the fatigue crack growth behavior of the alloy in three environments, more brittle striations were observed in humidity air and salt spray. The increased crack growth rate was attributed to a combination of hydrogen embrittlement and anodic dissolution at the tip of crack.

We describe an analytical method of vascular smooth muscle cell membrane chromatography (VSM/CMC) combined with gas chromatography/mass spectrometry (GC/MS) for recognition, separation and identification of active components from traditional Chinese medicines (TCMs). VSM cells by means of primary culture with rat thoracic aortas were used for preparation of the stationary phase in the CMC model. Retention components by the VSM-CMC model were collected and then analyzed by GC/MS under the optimized conditions in offline conditions. After investigating the suitability and reliability of the VSM/CMC-offline-GC/MS method using nifedipine and nitrendipine as standard compounds, this method was applied in screening active components from the extracts of TCMs such as Radix Angelicae Dahuricae (RAD), Rhizomza Seu Radix Notopterygii (RSRN), Radix Glehniae (RG) and Fructus Cnidii (FC). Retention components from the extracts in the VSM-CMC model were imperatorin and osthole identified by the GC/MS method. In vitro pharmacological trials indicated that imperatorin and osthole could concentration dependently relax the rat thoracic artery pre-contracted by KCl (P

Background and objective We conducted epidemiologic investigations and serologic assays on household contacts that were extensively exposed to three influenza A (H7N9) virus infected case-patients before infection-control practices were implemented. Study design Data on the early clinical course of each patient and the exposure history for each patient's household contacts were obtained by interviewing household members and by reviewing medical records. Viral RNA in patient samples was tested using real-time reverse transcriptase polymerase chain reaction assay. Antibodies against H7N9 virus in serum samples were tested using hemagglutination inhibition and pseudovirus based neutralization assays. Results All household contacts were extensively exposed to the case-patients without the use of measures to protect against infection. Viral RNA was detected in the specimens from case-patients for approximately 7–11 days after confirmation of infection. However, the results of the analyses of serum specimens taken from the household contacts 15–26 days post exposure revealed no evidence of transmission of H7N9 virus from the case-patients to the contacts. Conclusion Despite ample unprotected exposures to case-patients during the virus shedding period, household members in this report were not infected by the H7N9 virus.

Few studies on the humoral immune responses in human during natural influenza infection have been reported. Here, we used serum samples from pandemic 2009 H1N1 influenza infected patients to characterize the humoral immune responses to influenza during natural infection in humans. We observed for the first time that the pandemic 2009 H1N1 influenza induced influenza A-specific IgM within days after symptoms onset, whereas the unit of IgG did not changed. The magnitude of influenza A-specific IgM antibodies might have a value in predicting the rate of virus clearance to some degree. However, the newly developed IgM was not associated with hemagglutination inhibition (HI) activities in the same samples but correlated with HI activities of subsequently collected sera which were mediated by IgG antibodies, indicating that IgM was critical for influenza infection and influences subsequent IgG antibody responses. These findings provide new important insights on the human immunity to natural influenza infection.

Transmission plays a central role in the ecology of baculoviruses and the population dynamics of their hosts. Here, we report on the horizontal and vertical transmission dynamics of wild-type Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HaSNPV-WT) and a genetically modified variant (HaSNPV-AaIT) with enhanced speed of action through the expression of an insect-selective scorpion toxin (AaIT). In caged field plots, horizontal transmission of both HaSNPV variants was greatest when inoculated 3rd instar larvae were used as infectors, transmission was intermediate with 2nd instar infectors and lowest with 1st instar infectors. Transmission was greater at a higher density of infectors (1 per plant) than at a lower density (1 per 4 plants); however, the transmission coefficient (number of new infections per initial infector) was lower at the higher density of infectors than at the lower density. HaSNPV-AaIT exhibited a significantly lower rate of transmission than HaSNPV-WT in the field cages. This was also the case in open field experiments. In the laboratory, the vertical transmission of HaSNPV-AaIT from infected females to offspring of 16.7 ± 2.1% was significantly lower than that of HaSNPV-WT (30.9 ± 2.9%). Likewise, in the field, vertical transmission of HaSNPV-AaIT (8.4 ± 1.1%) was significantly lower than that of HaSNPV-WT (12.6 ± 2.0%). The results indicate that the recombinant virus will be transmitted at lower rates in H. armigera populations than the wild-type virus. This may potentially affect negatively its long-term efficacy as compared to wild-type virus, but contributing positively to its biosafety.

To determine whether CRF07_BC, one of the most predominant strains that accounts for one third HIV-1 prevalence in China, has the ability to infect hematopoietic progenitor cells (HPCs), human Umbilical Cord Blood (UCB) derived CD34+ HPCs isolated with high purity were infected by HIV-1 pseudotyped with CRF07_BC envelope. After HIV-1 infection, ~0.86% CD34+ HPCs were co-stained for CD34 and intracellular HIV Gag. HIV p24 antigen was detectable and reached maximal release between day 2-4 after HIV-1 infection. The data of nested Alu-LTR PCR proved the integration of HIV-1 genome into the host genome occurred in HIV-1-infected HPCs. These data demonstrated that the envelope of CRF07_BC from China has the capability of resulting in infection to CD34+ HPCs, which may serve as a mechanism for long-term latency of HIV-1 infection in vivo.