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Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g−1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required.

The information security has an irreplaceable position in the smart grid (SG). In order to avoid the malicious attack and ensure the information security, the cryptographic techniques are essential. This paper focuses on the encryption techniques to ensure the information security of SG. Firstly, an unusual 7-dimensional complex chaotic system (7D-CCS) combined with the cubic memristor is introduced. Besides its phase portraits, Lyapunov exponent, 0–1 test, complexity, and bifurcation diagram are investigated. Then, with the proposed 7D-CCS, we design a data encryption algorithm to ensure the encryption security. Finally, the data and monitoring images in SG are encrypted by the designed encryption scheme. Besides, the encryption performance is given in detailed. The experimental results show that the proposed encryption scheme has quite good encryption performance. Therefore, it can ensure the information security of SG.

Spatial audio has attracted more and more attention in the fields of virtual reality (VR), blind navigation and so on. The individualized head-related transfer functions (HRTFs) play an important role in generating spatial audio with accurate localization perception. Existing methods only focus on one database, and do not fully utilize the information from multiple databases. In light of this, a pre-trained-based individualization model is proposed to predict HRTFs for any target user in this paper, and a real-time spatial audio rendering system built on a wearable device is implemented to produce an immersive virtual auditory display. The proposed method first builds a pre-trained model based on multiple databases using a DNN-based model combined with an autoencoder-based dimensional reduction method. This model can capture the nonlinear relationship between user-independent HRTFs and position-dependent features. Then, fine tuning is done using a transfer learning technique at a limit number of layers based on the pre-trained model. The key idea behind fine tuning is to transfer the pre-trained user-independent model to the user-dependent one based on anthropometric features. Finally, real-time issues are discussed to guarantee a fluent auditory experience during dynamic scene update, including fine-grained head-related impulse response (HRIR) acquisition, efficient spatial audio reproduction, and parallel synthesis and playback. These techniques ensure that the system is implemented with little computational cost, thus minimizing processing delay. The experimental results show that the proposed model outperforms other methods in terms of subjective and objective metrics. Additionally, our rendering system runs on HTC Vive, with almost unnoticeable delay.

The cytokine network of tumour microenvironment (TME) plays an important role in cancer growth and progression. The current work aims to provide a new strategy for cancer therapy based on the targeted regulation of cytokines in the TME. Here, heparin-coupled polyvinyl alcohol (PVA-H) microspheres have been developed as an adsorbent for selectively remove tumour-induced immunosuppressive cytokines, such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), but not tumour necrosis factor-alpha (TNF-α) which has an immune-stimulating effect and can inhibit tumour growth. The proliferation and apoptosis of breast cancer cells after perfusion were tested by cell viability assays, flow cytometry analysis and mRNA microarray assays. Results showed that the PVA-H microspheres efficiently absorbed the majority of VEGF (74.39%) and TGF-β (86.39%), but much less TNF-α (4.16%). The regulation of the cytokines had remarkable anti-proliferative and pro-apoptotic effects on breast cancer cells, which was further confirmed from the change of mRNA expression levels. Thus, targeting regulatory pathways within the TME by an affinity adsorbent that selectively depletes immunosuppressive cytokines is potentially a new and promising strategy for cancer therapy.

Although atherosclerosis is a multifactorial process, proteoglycans mediated lipoprotein (LDL) retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation. Proteoglycans (PGs) are usually composed of one core protein backbone with one or more glycosaminoglycan chains (GAGs) covalently linked, mainly include perlecan, biglycan, versican, and decorin. The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100, the moiety of LDL, electrostatic interacting with the negatively charged GAGs (sulfate or carbohydrate groups) of proteoglycans or though some bridge molecules like sphingomyelinase (SMase) or lipoprotein lipase (LpL). In the later section, we collate the promising therapeutic approaches that have been proposed up to now, targeting LDL-PGs interaction. It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan, biglycan, decorin, and versican that all located in the extracellular matrix (ECM), future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs, seeking promising therapeutic targets more specifically.

Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1–2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL-cholesterol levels and that a polymorphism within the HL promoter (−514C→T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The −514C→T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors. —Allayee, H., K. M. Dominguez, B. E. Aouizerat, R. M. Krauss, J. I. Rotter, J. Lu, R. M. Cantor, T. W. A. de Bruin, and A. J. Lusis. Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.

In China, the English Test Band 6 (CET6) is a national test that is used to assess the English proficiency of test-takers by the state with unified questions, unified fees, and unified organization of tests. It is held twice a year. This test has had a great impact on college students and college teachers. It was introduced in 1978. In 2016, the Ministry of Education reformed CET-6, especially in listening tests. The reformed listening test not only brings scenes and dialogues closer to daily life but also emphasizes the examination of students' comprehensive English listening and speaking ability. From the perspective of learners, this paper draws on the theoretical models and empirical results of washback at home and abroad and studies the backwash of the reformed English CET-6 listening to learners' listening learning through a questionnaire. To do the survey, the paper was surveyed by quantitative research methods with 60 samples in several public universities. After the collection and analysis of data, the authors have affirmed and determined this test has a significant washback effect on student learning.

The traffic signs transfer trip information to drivers through vectors like words, graphs and numbers. Traffic sign with excessive information often makes the drivers have no time to read and understand, leading to risky driving. It is still a problem of how to clarify the relationship between traffic sign recognition and risky driving behavior. This paper presents a study that is reflective of such an effort. Twenty volunteers participated in the dynamic visual recognition experiment in driving simulator, and the data of several key indicators are obtained, including visual cognition time, vehicle acceleration and the offset distance from middle lane, etc. Correlations between each indicator above are discussed in terms of risky driving. Research findings directly show that drivers' behavior changes a lot during their traffic sign recognition.

Abstract Background One-pot synthesis of metal nanoparticles under ambient temperature and pressure using reducing and stabilizing materials from microbes is energy-effective and ecofriendly, but upstream extraction of biological raw materials and downstream purification of nanoparticles from bioreactors are laborious and expensive. To simplify the productive process for using metal nanoparticles as microbicides to control plant pathogens, we use an endospore-forming Bacillus biocontrol agent to produce the nano-microbicide and use the bacterial raw materials as bio-microbicides together with the nano-microbicide. Results Bacillus cells at the stationary phase form endospores and tolerate Ag+ and Ag nanoparticles (AgNPs), while the cell-free culture supernatant (CFCS) mediates the synthesis of AgNPs. AgNPs produced from the Bacillus culture and CFCS show similar physical, chemical, and electrical characteristics, and bactericidal and anti-biofilm activities. Moreover, the diluted products effectively protect the kiwifruit leaves from the infection of the pathogen Pseudomonas syringae pv. actinidiae. Conclusions This coproduction of bio-microbicide and nano-microbicide is a totally green one-pot synthesis process without extraction and purification and without production of waste and can be easily scaled up using the existing fermentation processing of Bacillus biocontrol agents. The application of the synergistic bio-microbicide and nano-microbicide can effectively control the bacterial canker disease of kiwifruit plants. Graphical Abstract

Bacteriophage (phage) AP1 has been reported to effectively lyse Acidovorax oryzae, the causative agent of bacterial brown stripe in rice. However, phage AP1 exhibits strain-specific lysis patterns. In order to enhance the potential of phages for biological control of rice bacterial brown stripe, this study investigated the possible mechanism of strain-specific infection by characterizing phage AP1 and its susceptible (RS-2) and resistant (RS-1) strains. Based on the current classification standards and available database information, phage AP1 was classified into the class Caudoviricetes, and it is a kind of podophage. Comparative analysis of the susceptible and resistant strains showed no significant differences in growth kinetics, motility, biofilm formation, or effector Hcp production. Interestingly, the resistant strain demonstrated enhanced virulence compared to the susceptible strain. Prokaryotic expression studies indicated that six putative structural proteins of phage AP1 exhibited varying degrees of binding affinity (1.90–9.15%) to lipopolysaccharide (LPS). However, pull-down assays and bacterial two-hybrid analyses revealed that only gp66 can interact with four host proteins, which were identified as glycosyltransferase, RcnB, ClpB, and ImpB through immunoprecipitation and mass spectrometry analyses. The role of LPS in the specific infection mechanism of phage AP1 was further elucidated through the construction of knockout mutant strains and complementary strains targeting a unique gene cluster (wbzB, wbzC, wbzE, and wbzF) involved in LPS precursor biosynthesis. These findings provide novel insights into the mechanisms of phage-host specificity, which are crucial for the effective application of phage AP1 in controlling rice bacterial brown stripe.

Erwinia amylovora, the causative agent of fire blight, causes significant economic losses for farmers worldwide by inflicting severe damage to the production and quality of plants in the Rosaceae family. Historically, fire blight control has primarily relied on the application of copper compounds and antibiotics, such as streptomycin. However, the emergence of antibiotic-resistant strains and growing environmental concerns have highlighted the need for alternative control methods. Recently, there has been a growing interest in adopting bacteriophages (phages) as a biological control strategy. Phages have demonstrated efficacy against the bacterial plant pathogen E. amylovora, including strains that have developed antibiotic resistance. The advantages of phage therapy includes its minimal impact on microbial community equilibrium, the lack of a detrimental impact on plants and beneficial microorganisms, and its capacity to eradicate drug-resistant bacteria. This review addresses recent advances in the isolation and characterization of E. amylovora phages, including their morphology, host range, lysis exertion, genomic characterization, and lysis mechanisms. Furthermore, this review evaluates the environmental tolerance of E. amylovora phages. Despite their potential, E. amylovora phages face certain challenges in practical applications, including stability issues and the risk of lysogenic conversion. This comprehensive review examines the latest developments in the application of phages for controlling fire blight and highlights the potential of E. amylovora phages in plant protection strategies.

Xanthomonas oryzae pv. oryzae (Xoo) is a significant bacterial pathogen responsible for outbreaks of bacterial leaf blight in rice, posing a major threat to rice cultivation worldwide. Effective management of this pathogen is crucial for ensuring rice yield and food security. In this study, we identified and characterized a novel Xoo phage, ZP3, isolated from diseased rice leaves in Zhejiang, China, which may offer new insights into biocontrol strategies against Xoo and contribute to the development of innovative approaches to combat bacterial leaf blight. Transmission electron microscopy indicated that ZP3 had a short, non-contractile tail. Genome sequencing and bioinformatic analysis showed that ZP3 had a double-stranded DNA genome with a length of 44,713 bp, a G + C content of 52.2%, and 59 predicted genes, which was similar to other OP1-type Xoo phages belonging to the genus Xipdecavirus. ZP3’s endolysin LysZP was further studied for its bacteriolytic action, and the N-terminal transmembrane domain of LysZP is suggested to be a signal–arrest–release sequence that mediates the translocation of LysZP to the periplasm. Our study contributes to the understanding of phage–Xoo interactions and suggests that phage ZP3 and its endolysin LysZP could be developed into biocontrol agents against this phytopathogen.

The surface of vascular endothelial cells (ECs) is covered by a protective negatively charged layer known as the endothelial glycocalyx. Herein, we hypothesized its transport barrier and mechanosensory role in transmural water flux and low-density lipoprotein (LDL) transport in an isolated rat abdominal aorta perfused under 85 mmHg and 20 dyn/cm2 ex vivo. The endothelial glycocalyx was digested by hyaluronidase (HAase) from bovine tests. Water infiltration velocity (Vw) was measured by a graduated pipette. LDL coverage and mean maximum infiltration distance (MMID) in the vessel wall were quantified by confocal laser scanning microscopy. EC apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and leaky junction rates were evaluated by electron microscopy. The results showed that a 42% degradation of the endothelial glycocalyx by HAase treatment increased Vw, LDL coverage, and MMID. Shear stress increased Vw, which cannot be inhibited by HAase treatment. Four hour-shear application increased about fourfolds of LDL coverage, whereas exerted no significant effects on its MMID, EC apoptosis, and the leaky junctions. On the contrary, 24-h shear exposure has no significant effects on LDL coverage, whereas increased 2.74-folds of MMID and about 53% of EC apoptotic rates that could be inhibited by HAase treatment. These results suggest endothelial glycocalyx acts as a transport barrier by decreasing water and LDL transport, as well as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport into the vessel wall. NEW & NOTEWORTHY A 42% degradation of the endothelial glycocalyx by hyaluronidase of the isolated rat abdominal aorta facilitated water and LDL transport across the vessel wall, suggesting endothelial glycocalyx as a transport barrier. A 24-h shear exposure increased LDL mean maximum infiltration distance, and enhanced EC apoptosis, which could be both inhibited by hyaluronidase treatment, suggesting endothelial glycocalyx may also act as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport. [ABSTRACT FROM AUTHOR]

ABSTRACT Rice bacterial leaf blight (BLB) is the most destructive phyllosphere bacterial disease caused by Xanthomonas oryzae pv. oryzae. The effect of soil-borne diseases on the rhizosphere microbiome has been extensively investigated. However, the regulatory role of the phyllosphere disease BLB on the rhizosphere microbiome remains unclear. Here, we observed that BLB significantly altered the composition of the bacterial-fungal community in the rhizosphere, decreasing bacterial diversity but not fungal diversity. The scale of inter-kingdom networks in the rhizosphere microbiome of BLB-infected plants was more complex and broader than in healthy plants, while the bacterial community was more vulnerable to BLB than the fungal community. Indeed, the relative abundance of Streptomyces, Chitinophaga, Sphingomonas, and Bacillus was higher in the BLB rhizosphere, which can be explained by their keystone hub taxa status in the rhizosphere co-occurrence network. Null model analysis showed that the deterministic assembly of bacterial communities increased while that of fungi decreased. Additionally, the assembly of bacterial and fungal communities was significantly related to variations in BLB and soil nutrients, especially pH and available phosphorus. Random forest model results showed that the bacterial community in the rhizosphere had a strong potential for predicting BLB. Metagenomic analysis revealed that BLB had a considerable impact on the functional adaptation of the rhizosphere microbiome. Interestingly, the abundance of some functional genes involved in carbon, phosphorus, and methane metabolism increased drastically. IMPORTANCE Our results suggest that rhizosphere bacteria are more sensitive to bacterial leaf blight (BLB) than fungi. BLB infection decreased the diversity of the rhizosphere bacterial community but increased the complexity and size of the rhizosphere microbial community co-occurrence networks. In addition, the relative abundance of the genera Streptomyces, Chitinophaga, Sphingomonas, and Bacillus increased significantly. Finally, these findings contribute to the understanding of plant-microbiome interactions by providing critical insight into the ecological mechanisms by which rhizosphere microbes respond to phyllosphere diseases. In addition, it also lays the foundation and provides data to support the use of plant microbes to promote plant health in sustainable agriculture, providing critical insight into ecological mechanisms.

Abstract Plant growth-promoting rhizobacteria (PGPR) or Biocontrol strains inevitably encounter heavy metal excess stress during the product’s processing and application. Bacillus amyloliquefaciens Bam1 was a potential biocontrol strain with strong heavy metal resistant ability. To understand its heavy metal resistance mechanism, the complete genome of Bam1 had been sequenced, and the comparative genomic analysis of Bam1 and FZB42, an industrialized PGPR and biocontrol strain with relatively lower heavy metal tolerance, was conducted. The comparative genomic analysis of Bam1 and the other nine B. amyloliquefaciens strains as well as one Bacillus velezensis (genetically and physiologically very close to B. amyloliquefaciens) was also performed. Our results showed that the complete genome size of Bam1 was 3.95 Mb, 4219 coding sequences were predicted, and it possessed the highest number of unique genes among the eleven analyzed strains. Nine genes related to heavy metal resistance were detected within the twelve DNA islands of Bam1, while only two of them were detected within the seventeen DNA islands of FZB42. When compared with B. amyloliquefaciens type strain DSM7, Bam1 lacked contig L, whereas FZB42 lacked contig D and I, as well as just possessed contig B with a very small size. Our results could also deduce that Bam1 promoted its essential heavy metal resistance mainly by decreasing the import and increasing the export of heavy metals with the corresponding homeostasis systems, which are regulated by different metalloregulators. While Bam1 promoted its non-essential heavy metal resistance mainly by the activation of some specific or non-specific exporters responding to different heavy metals. The variation of the genes related to heavy metal resistance and the other differences of the genomes, including the different number and arrangement of contigs, as well as the number of the heavy metal resistant genes in Prophages and Genomic islands, led to the significant different resistance of Bam1 and FZB42 to heavy metals. Graphical Abstract

Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to the production of greenhouse cucumber and other Cucurbitaceae crops worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and adjacent plants by mechanical contact between the foliage of diseased and healthy plants, causing extensive yield losses. An accurate method for detecting and quantifying this virus is urgently needed to ensure the safety of the global seed trade. Here, we report the development of a reverse-transcription droplet digital polymerase chain reaction (RT-ddPCR)-based method for specific and high-sensitive detection of CGMMV. By testing three primer–probe sets and optimizing reaction conditions, we showed that the newly developed RT-ddPCR method is highly specific and sensitive, with a detection limit of 1 fg/μL (0.39 copy/μL). The sensitivity of the RT-ddPCR method was compared with that of real-time fluorescence quantitative RT-PCR (RT-qPCR) using a series of plasmid dilutions and total RNAs extracted from infected cucumber seeds, and the detection limit of RT-ddPCR was 10 times higher than RT-qPCR with plasmid dilutions and 100 times higher than RT-qPCR for detecting CGMMV from infected cucumber seeds. The RT-ddPCR method was further assessed for detecting CGMMV from a total of 323 samples of Cucurbitaceae seeds, seedlings, and fruits as compared with the RT-qPCR method. We found that the infection rate of CGMMV on symptomatic fruits was as high as 100%, whereas infection rates were lower for seeds and lowest for seedlings. Notably, the results of two methods in detecting CGMMV from different cucurbit tissues showed the high consistency with Kappa value from 0.84 to 1.0, demonstrating that the newly developed RT-ddPCR method is highly reliable and practically useful for large-scale CGMMV detection and quantification.

There are many emergency risks in the process of natural gas hydrate (NGH) drilling. In order to ensure the safe and efficient exploitation of NGH, it is urgent to establish an intelligent judgment method for the risks in the process of NGH drilling. In this paper, the response relationship between monitoring parameters and risk categories of NGH while drilling is established. Based on fuzzy analytic hierarchy process (FAHP), the comprehensive weights of 10 risk monitoring parameters are obtained, including gas production, wellbore instability, hydrate ice barrier, drill string fracture, sticking, bit balling, drilling tool piercement, gas seepage, seabed subsidence and seabed landslide. Besides, the comprehensive judgment weight matrix is constructed, and the reasonable fluctuation range of monitoring parameters is formed. Thus, the intelligent judgment method of NGH drilling risk is established. The intelligent judgment and alarm of NGH drilling risks can be realized quickly and accurately by this method, namely, it can monitor the risks in the process of operation and guarantee the construction safety of NGH drilling.

Some endophyte bacteria can improve plant growth and suppress plant diseases. However, little is known about the potential of endophytes bacteria to promote wheat growth and suppress the Fusarium seedling blight pathogen Fusarium graminearum. This study was conducted to isolate and identify endophytic bacteria and evaluate their efficacy for the plant growth promotion and disease suppression of Fusarium seedling blight (FSB) in wheat. The Pseudomonas poae strain CO showed strong antifungal activity in vitro and under greenhouse conditions against F. graminearum strain PH-1. The cell-free supernatants (CFSs) of P. poae strain CO were able to inhibit the mycelium growth, the number of colonies forming, spore germination, germ tube length, and the mycotoxin production of FSB with an inhibition rate of 87.00, 62.25, 51.33, 69.29, and 71.08%, respectively, with the highest concentration of CFSs. The results indicated that P. poae exhibited multifarious antifungal properties, such as the production of hydrolytic enzymes, siderophores, and lipopeptides. In addition, compared to untreated seeds, wheat plants treated with the strain showed significant growth rates, where root and shoot length increased by about 33% and the weight of fresh roots, fresh shoots, dry roots, and dry shoots by 50%. In addition, the strain produced high levels of indole-3-acetic acid, phosphate solubilization, and nitrogen fixation. Finally, the strain demonstrated strong antagonistic properties as well as a variety of plant growth-promoting properties. Thus, this result suggest that this strain could be used as an alternate to synthetic chemicals, which can serve as an effective method of protecting wheat from fungal infection.

Targeted genome editing technologies are becoming the most important and widely used genetic tools in studies of phytopathology. The “clustered regularly interspaced short palindromic repeats (CRISPR)” and its accompanying proteins (Cas) have been first identified as a natural system associated with the adaptive immunity of prokaryotes that have been successfully used in various genome-editing techniques because of its flexibility, simplicity, and high efficiency in recent years. In this review, we have provided a general idea about different CRISPR/Cas systems and their uses in phytopathology. This review focuses on the benefits of knock-down technologies for targeting important genes involved in the susceptibility and gaining resistance against viral, bacterial, and fungal pathogens by targeting the negative regulators of defense pathways of hosts in crop plants via different CRISPR/Cas systems. Moreover, the possible strategies to employ CRISPR/Cas system for improving pathogen resistance in plants and studying plant–pathogen interactions have been discussed.