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Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

The preparation method of integrated circuit lead frames has transitioned from stamping to etching, rendering them more sensitive to residual stress. Consequently, the dimensional deviations caused by residual stress become more pronounced, necessitating a thorough investigation into the copper strip processing process, particularly considering the high-precision requirements of the lead frame. A quasi in situ method was employed to monitor the deformation process, and quantitative analyses and graphical reconstructions of the residual stress were conducted. The results indicated that the orientation evolution did not exhibit a significant correlation with grain size or grain aspect ratio. However, the stored energy of the different grains was related to their orientations. Further analysis of slip traces revealed that single or multiple slipping may be activated in grain subdivisions, and the Schmid factor difference ratio (SFDR) value proved to be an effective tool for analyzing this deformation mode. An even more interesting finding was that the deformation mode directly affected the residual stress distribution in local regions. The relationship between residual stress, Schmid factor, and SFDR was further analyzed, and a clear correlation between SFDR and residual stress was found in this study.

Cu–15Ni–8Sn alloy is the best choice to replace beryllium bronze alloy. This alloy has unparalleled application value in aerospace, ocean engineering, electronic information, equipment manufacturing, and other fields. However, the application of Cu–15Ni–8Sn alloy is challenged and limited because of a series of problems in its preparation and processing, such as easy segregation, difficult deformation, and discontinuous precipitation. It is an effective way to improve the comprehensive properties of Cu–15Ni–8Sn alloy using alloying design and process optimization to control the as-cast, deformed, and heat-treated microstructures. At present, it is a hot spot for scholars to study. In this paper, the grade generation, system evolution, and preparation technology development of Cu–15Ni–8Sn alloy are comprehensively reviewed. The phase transformation sequence of the Cu–15Ni–8Sn alloy is discussed. The influence of the type, amount, and existing form of alloying elements on the strength of Cu–15Ni–8Sn alloy and its mechanism are systematically summarized. Furthermore, the latest research progress on the effects of solid solution, cold deformation, and aging on the phase structure transformation and mechanical properties of Cu–15Ni–8Sn alloy is summarized. Finally, the future development trend of the Cu–15Ni–8Sn alloy is projected. The research results of this paper can provide a reference for the control of the microstructure and properties of high-performance Cu–15Ni–8Sn alloys used in key fields, as well as the optimization of the preparation process and alloy composition.

The porcine epidemic diarrhea virus (PEDV) is a highly contagious and virulent enteric coronavirus that causes severe enteric disease in pigs worldwide. PEDV infection causes profound diarrhea, vomiting, and dehydration in pigs of all ages, resulting in high mortality rates, particularly among neonatal piglets. The spike glycoprotein (S) of PEDV plays a crucial role in binding to the host cell receptor and facilitating fusion between the viral and host membranes. Pseudotyped viral particles featuring the PEDV S protein are valuable tools for investigating virus entry, identifying neutralizing antibodies, and developing small molecules to impede virus replication. In this study, we used a codon-optimized PEDV S protein to generate recombinant pseudotyped vesicular stomatitis virus (VSV) particles (rVSV-ΔG-EGFP-S). The full-length S protein was efficiently incorporated into VSV particles. The S protein pseudotyped VSV exhibited infectivity towards permissive cell lines of PEDV. Moreover, we identified a new permissive cell line, JHH7, which showed robust support for PEDV replication. In contrast to the SARS-CoV-2 spike protein, the removal of amino acids from the cytoplasmic tail resulted in reduced efficiency of viral pseudotyping. Furthermore, we demonstrated that 25-hydroxycholesterol inhibited rVSV-ΔG-EGFP-S entry, while human APN facilitated rVSV-ΔG-EGFP-S entry through the use of ANPEP knockout Huh7 cells. Finally, by transducing swine intestinal organoids with the rVSV-ΔG-EGFP-S virus, we observed efficient infection of the swine intestinal organoids by the PEDV spike-pseudotyped VSV. Our work offers valuable tools for studying the cellular entry of PEDV and developing interventions to curb its transmission.

In this work, a reconfigurable ultra-wideband transmissive terahertz polarization rotator based on graphene metamaterial is proposed that can switch between two states of polarization rotation within a broad terahertz band by changing the Fermi level of graphene. The proposed reconfigurable polarization rotator is based on a two-dimensional periodic array of multilayer graphene metamaterial structure, which is composed of metal grating, graphene grating, silicon dioxide thin film, and a dielectric substrate. The graphene metamaterial can achieve high co-polarized transmission of a linearly polarized incident wave at the off-state of the graphene grating without applying the bias voltage. Once the specially designed bias voltage is applied to change the Fermi level of graphene, the polarization rotation angle of linearly polarized waves is switched to 45° by the graphene metamaterial at the on-state. The working frequency band with 45-degree linear polarized transmission remaining above 0.7 and the polarization conversion ratio (PCR) above 90% is from 0.35 to 1.75 THz, and the relative bandwidth reaches 133.3% of the central working frequency. Furthermore, even with oblique incidence at large angles, the proposed device retains high-efficiency conversion in a broad band. The proposed graphene metamaterial offers a novel approach for the design of a terahertz tunable polarization rotator and is expected to be applied in the applications of terahertz wireless communication, imaging, and sensing.

A duplicate diet collection method was used to estimate dietary exposure to glutamates in children aged 2–5 years in selected provinces of China. Daily duplicate diet samples were collected from 86 healthy toddlers over three consecutive days. Glutamates were analyzed using ultra-high-pressure liquid chromatography–MS/MS (UHPLC–MS/MS). Results showed that the highest glutamates content was found in mixed meals, at 5.12 mg/kg, followed by powdered formula (3.89 mg/kg), and milk and dairy products (2.29 mg/kg). The total mean daily dietary exposure for subjects was 0.20 mg/kg BW, and P95 daily dietary exposure was 0.44 mg/kg BW, both below the acceptable daily intake (ADI) (120 mg/kg BW) recommended by the Joint (FAO/WHO) Expert Committee on Food Additives (JECFA) and the ADI (30 mg/kg BW) set by the European Food Safety Authority (EFSA). Hence it can be considered that glutamates exposure would cause low risk in this group.

Cancer is a leading cause of death worldwide, posing a huge burden upon society and individuals. The adequate intake of fruit and vegetables is reported to be an effective strategy for primary cancer prevention. Fruits and vegetables are rich in nutrients, such as vitamins and flavonoids, which may reduce the occurrence and progression of cancers. However, the importance of each flavonoid and the sub-classes remains controversial regarding cancer mortality. The population benefiting from increased flavonoid intake has not been determined. An estimation of cancer mortality by flavonoid intake is not established. We explored the association between the intake of flavonoids and cancer mortality amongst 14,029 participants in the National Health and Nutrition Examination Survey. During a median follow-up of 117 months, 405 cancer deaths were confirmed. Being in the second, third, and fourth quartiles of flavonol intake, the cancer mortality was inversely associated with the intake of flavonols (multivariate analysis HR (95% CI] 0.58 [0.36, 0.91], p = 0.02, Q1 vs. Q2; 0.55 [0.31, 0.96], p = 0.04, Q1 vs. Q3; 0.54 [0.30, 0.99], p = 0.05, Q1 vs. Q4, respectively). Potential effects of dietary flavonol intake against cancer death was observed especially in participants aged 50 or above, males, whites, former smokers, people who used to drink or drink alcohol mildly, people without hyperlipidemia, and people with hypertension. Moreover, the dietary intakes of peonidin, naringenin, and catechin were inversely associated with cancer mortality (multivariate HR [95% CI] 0.93 [0.88,0.98], p = 0.01; 0.97 (0.95,1.00), p = 0.03; 0.98 (0.96,1.00), p = 0.05, respectively). Furthermore, a nomogram based on flavonol intake is feasible for assessing cancer mortality for each participant. Taken together, our results could improve personalized nutrition amongst cancer patients.

Since 2018, the outbreak and prevalence of the African swine fever virus (ASFV) in China have caused huge economic losses. Less virulent ASFVs emerged in 2020, which led to difficulties and challenges for early diagnosis and control of African swine fever (ASF) in China. An effective method of monitoring ASFV antibodies and specific antibodies against ASFV to promote the development of prevention techniques are urgently needed. In the present study, ASFV p17 was successfully expressed in CHO cells using a suspension culture system. An indirect enzyme-linked immunosorbent assay (ELISA) based on purified p17 was established and optimized. The monoclonal antibody (mAb) against p17 recognized a conservative linear epitope (3TETSPLLSH11) and exhibited specific reactivity, which was conducive to the identification of recombinant porcine reproductive and respiratory syndrome virus (PRRSV) expressing p17. The ELISA method efficiently detected clinical ASFV infection and effectively monitored the antibody levels in vivo after recombinant PRRSV live vector virus expressing p17 vaccination. Overall, the determination of the conserved linear epitope of p17 would contribute to the in-depth exploration of the biological function of the ASFV antigen protein. The indirect ELISA method and mAb against ASFV p17 revealed efficient detection and promising application prospects, making them ideal for epidemiological surveillance and vaccine research on ASF.

Porcine reproductive and respiratory syndrome (PRRS) is an important viral disease, causing significant economic losses to the swine industry worldwide. Atypical cases caused by highly pathogenic PRRS virus (HP-PRRSV) emerged in 2006 in China. The vaccine strain HuN4-F112 has been developed from the wild-type HP-PRRSV HuN4 through repeated passages on MARC-145 cells. However, the mechanisms of attenuation have yet to be defined. Previous studies have shown that the vaccine strain HuN4-F112 could not effectively replicate in porcine alveolar macrophages (PAMs). In the present study, a series of chimeric and mutant PRRSVs were constructed to investigate regions associated with the virus attenuation. Firstly, the corresponding genome regions (ORF1a, ORF1b and ORFs 2-7) were exchanged between two infectious clones of HuN4 and HuN4-F112, and then the influence of small regions in ORF1a and ORF2-7 was evaluated, then influence of specific amino acids on NSP2 was tested. NSP2 was determined to be the key gene that regulated infection efficiency on PAMs, and amino acids at 893 and 979 of NSP2 were the key amino acids. The results of in vivo study indicated that NSP2 was not only important for infection efficiency in vitro, but also influenced the virulence, which was indicated by the results of survival rate, temperature, viremia, lung score and tissue score.

To reliably realize the functions of autonomous navigation and cruise of logistics robots in a complex logistics storage environment, this paper proposes a new robot navigation system based on vision and multiline lidar information fusion, which can not only ensure rich information and accurate map edges, but also meet the real-time and accurate positioning and navigation in complex logistics storage scenarios. Simulation and practical verification showed that the robot navigation system is feasible and robust, and overcomes the problems of low precision, poor robustness, weak portability, and difficult expansion of the mobile robot system in a complex environment. It provides a new idea for inspection in an actual logistics storage scenario and has a good prospective application.

The aircraft control system of the future will be a combination of fly-by-wire technology and Active Control System (ACS) which, based on the artificial feel system, provides a control strategy for both position and force. The ACS has uncertainties, such as the mass of the simulated stick, system inertia, system damping and friction. In this paper, aiming at the servo control method of ACS, a mathematical model of ACS was setup. Then, to eliminate the perturbation of the external environment, such as noise and disturbance torque, a robust control method based on H∞ was proposed. Finally, to verify the simulation results, the mathematical model was verified via experimental studies.

The present work aims to systematically investigate the influence of P content on the microstructure and texture evolution of oxygen-free copper during intermediate annealing and final cold rolling. The microstructure and texture evolution were studied by electron backscattered diffraction and transmission electron microscopy. With the addition of P, the grains refined and a large fraction of low angle grain boundaries (LAGBs) emerged after intermediate annealing. The texture transformed from pure metal type for pure Cu to the α-fiber texture which included brass and Goss texture as P was added. The recrystallization temperature increased with the addition of P, and refined grains after the final cold rolling process. The addition of elemental P would reduce the stacking fault energy, and then influence the transformation of the deformation and recrystallization texture of the copper. Accompanied by the evolution of the deformation texture, the recrystallization cubic texture {001} was suppressed and a strong {236} brass recrystallization texture emerged with the addition of elemental P after the intermediate annealing and subsequent final cold rolling process.

A compression experiment with electron backscatter diffraction (EBSD) measurements was designed to characterize the effect of the microtexture on the grain rotation process. The rotation degrees of more than 180 grains before and after the compression were calculated. Results showed that grains with different crystallographic orientations experienced various rotation degrees. Furthermore, grains in certain microtexture regions also had varying degrees of rotation. The compression led to the lattice rotation and change in orientation of individual grains, but the relative misorientation between grains has not changed much in the microtexture region. The microtexture region, as a whole, participated in the compression process. The similar slipping behavior of the grains in the region promoted the slip transmission between the neighboring grains. Thus, the amount of piled-up dislocations at grain boundaries inside the microtexture region are less than that at grain boundaries outside the microtexture region, leading to a small stored energy density for grain boundaries inside the microtexture region.

Highly pathogenic porcine reproductive and respiratory syndrome virus PRRSV (HP-PRRSV) was one of the most devastating diseases of the pig industry, among various strategies, vaccination was one of the most useful tools for PRRS control. Attenuated live vaccine was used worldwide, however, the genetic basis of HP-PRRSV virulence change during attenuation remain to be determined. Here, to identify virulence associated regions of HP-PRRSV during attenuation in vitro, six full-length infectious cDNA clones with interchanges of 5′UTR + ORF1a, ORF1b, and ORF2-7 + 3′UTR regions between HP-PRRSV strain HuN4-F5 and its attenuated vaccine strain HuN4-F112 were generated, and chimeric viruses were rescued. Piglets were inoculated with chimeric viruses and their parental viruses, and rectal temperature were recorded daily, and serum were collected for future experiments. Our results showed that ORF1a played an important role on virus replication, cytokine response and lung damage, the exchange of ORF1b and ORF2-7 in different backbone led to different exhibition on virus replication in vivo/vitro and cytokine response. Among 9 PRRSV attenuated series, consistent amino acid changes during PRRSV attenuation were found in NSP4, NSP9, GP2, E, GP3 and GP4. Our study provides a fundamental data for the investigation of PRRSV attenuation, the different results of the virulence change among different studies indicated that different mechanisms might be used during PRRSV virulence enhancement in vivo and attenuation in vitro.

Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. Here, we report that platelet-derived ADAM17 (pADAM17) is regulated upon platelet activation of breast cancer patients, but not of healthy individuals. The observed downregulation of pADAM17 on platelets of cancer patients correlated with clinical parameters related to tumor progression including tumor stage and the occurrence of metastasis. Our data identify an association between platelet activation, modulation of platelet-derived ADAM17, and metastasis. In conclusion, we demonstrate that further development of pADAM17 as a liquid biomarker is warranted for monitoring disease progression in breast cancer.

Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in multiple malignancies, including about 85% of patients with estrogen receptor positive (ER+) breast cancer. Besides being studied as a prognostic marker, BCL-2 is investigated as a therapeutic target in ER+ breast cancer. Here, we introduce a new exosome-based strategy to target BCL-2 using genetically modified natural killer (NK) cells. The NK cell line NK92MI was lentivirally transduced to express and load BCL-2 siRNAs (siBCL-2) into exosomes (NKExos) and then evaluated for its potential to treat ER+ breast cancer. Transfected NK92MI cells produced substantial levels of BCL-2 siRNAs, without substantially affecting NK cell viability or effector function and led to loading of siBCL-2 in NKExos. Remarkably, targeting BCL-2 via siBCL-2 NKExos led to enhanced intrinsic apoptosis in breast cancer cells, without affecting non-malignant cells. Together, our prototypical results for BCL-2 in breast cancer provide proof of concept for a novel strategy to utilize NKExos as a natural delivery vector for siRNA targeting of oncogenes.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry worldwide. Our previous study had indicated that proprotein convertase subtilisin/kexin type 9 (PCSK9) was a responsive gene in porcine alveolar macrophages (PAMs) upon PRRSV infection. However, whether PCSK9 impacts the PRRSV replication and how the PRRSV modulates host PCSK9 remains elusive. Here, we demonstrated that PCSK9 protein suppressed the replication of both type-1 and type-2 PRRSV species. More specifically, the C-terminal domain of PCSK9 was responsible for the antiviral activity. Besides, we showed that PCSK9 inhibited PRRSV replication by targeting the virus receptor CD163 for degradation through the lysosome. In turn, PRRSV could down-regulate the expression of PCSK9 in both PAMs and MARC-145 cells. By screening the nonstructural proteins (nsps) of PRRSV, we showed that nsp11 could antagonize PCSK9’s antiviral activity. Furthermore, mutagenic analyses of PRRSV nsp11 revealed that the endoribonuclease activity of nsp11 was critical for antagonizing the antiviral effect of PCSK9. Collectively, our data provide further insights into the interaction between PRRSV and the cell host and offer a new potential target for the antiviral therapy of PRRSV.

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation.

The effects of aluminum on the mechanical properties and corrosion behavior in artificial seawater of Cu-Ni-Fe-Mn alloys were investigated. Cu-7Ni-xAl-1Fe-1Mn samples, consisting of 0, 1, 3, 5, and 7 wt % aluminum along with the same contents of other alloying elements (Ni, Fe, and Mn), were prepared. The microstructure of Cu-7Ni-xAl-1Fe-1Mn alloy was analyzed by Transmission Electron Microscopy (TEM), and its corrosion property was tested by an electrochemical system. The results show that the mechanical and corrosion properties of Cu-7Ni-xAl-1Fe-1Mn alloy have an obvious change with the aluminum content. The tensile strength has a peak value of 395 MPa by adding 3 wt % aluminum in the alloy. Moreover, the corrosion rate in artificial seawater of Cu-7Ni-3Al-1Fe-1Mn alloy is 0.0215 mm/a which exhibits a better corrosion resistance than the commercially used UNS C70600. It is confirmed that the second-phase transformation of Cu-7Ni-xAl-1Fe-1Mn alloy follows the sequence of α solid solution → Ni3Al → Ni3Al + NiAl → Ni3Al + NiAl3. The electrochemical impedance spectroscopy (EIS) shows that the adding element aluminum in the Cupronickel can improve the corrosion resistance of Cu-7Ni-xAl-1Fe-1Mn alloy.

The precipitation sequence of a Cu-Ni-Be alloy is: α-Cu supersaturated solid solution → Guinier-Preston (G.P.) zones → metastable γ″ → γ′ → stable γ (NiBe) phase. The micro-hardness and electrical conductivity during the aging process were measured. The precipitation characteristics and the distribution of the γ″ phase, under peak aging conditions, were analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area diffraction pattern (SADP), and high-resolution transmission electron microscopy (HRTEM). The results show that the orientation relationship of the γ″ phase/α-Cu matrix is: (001)p//(001)α; [100]p//[110]α (p: Precipitates, α: α-Cu supersaturated solid solution), which is in accordance with the Bain relationship in a FCC/BCC (face centered cubic/body centered cubic) structure, with the unique habit plane being {001}α. While the zone axis is parallel to [001]α, three forms of γ″ phases are distributed on the projection surface at the same time. The (001) reciprocal-lattice positions of γ″ phase in SADP are diffusely scattered, which is consistent with the variation of the d(001) value of the γ″ phase. The intra-range variation is related to the distortion of the (001) plane of the γ″ phase, due to interfacial dislocations and distortion strain fields. The lattice of the γ″ phase in the HRTEM images was measured as a = b = 0.259 ± 0.002 nm and c = 0.27–0.32 nm. With the increase of thermal exposure time, the stable γ phase has a NiBe phase structure (Standard Card Number: PDF#03-1098, a = b = c = 0.261 nm), and the long diffuse scattering spots will transform into single bright spots. The edge dislocation, generated by interfacial mismatch, promotes the formation of an optimal structure of the precipitated phase, which is the priority of growth in the direction of [110]p.