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Abstract Forecasting the remaining useful life (RUL) is a crucial aspect of prognostics and health management (PHM), which has garnered significant attention in academic and industrial domains in recent decades. The accurate prediction of RUL relies on the creation of an appropriate degradation model for the system. In this paper, a general representation of diffusion process models with three sources of uncertainty for RUL estimation is constructed. According to time-space transformation, the analytic equations that approximate the RUL probability distribution function (PDF) are inferred. The results demonstrate that the proposed model is more general, covering several existing simplified cases. The parameters of the model are then calculated utilizing an adaptive technique based on the Kalman filter and expectation maximization with Rauch-Tung-Striebel (KF-EM-RTS). KF-EM-RTS can adaptively estimate and update unknown parameters, overcoming the limits of strong Markovian nature of diffusion model. Linear and nonlinear degradation datasets from real working environments are used to validate the proposed model. The experiments indicate that the proposed model can achieve accurate RUL estimation results.

Fructose-1,6-diphosphate (FBP), a key glycolytic metabolite, is recognized for its cytoprotective effects during stress. However, the role of FBP in viral infections is unknown. Here, we demonstrate that virus-infected cells exhibit elevated FBP levels. Exogenous FBP inhibits both RNA and DNA virus infections in vitro and in vivo. Modulating intracellular FBP levels by regulating the expression of the metabolic enzymes FBP1 and PFK1 significantly impacts viral infections. Mechanistically, the inhibitory effects of FBP are not a result of altered viral adhesion or entry and are largely independent of type I interferon-mediated immune responses; rather, they occur through modulation of HMGB1. During viral infections, FBP predominantly reduces the protein levels of HMGB1 by facilitating its lysosomal degradation. Furthermore, FBP interacts with HMGB1 and disrupts the binding of HMGB1 to viral genomes, thereby further inhibiting viral replication. Our findings underscore the potential of FBP as a therapeutic target for controlling viral infections.

To improve the high-value application of millet bran, a water-soluble polysaccharide was extracted from fermented millet bran (FMBP) by using Bacillus natto fermentation. A neutral polysaccharide, FMBP-1, was separated and purified from FMBP using an anion exchange column. Its structure and antioxidant activity in vitro were characterized and determined. The molecular weight of FMBP-1 was 1.154 × 104 Da, and its molecular weight distribution was relatively uniform. The monosaccharide composition, FT-IR, methylation, and NMR results indicated that FMBP-1 was only composed of glucose and was an α-(1→4)-D-glucan that branched at O-6 with a terminal 1-linked α-D-Glcp as a side chain. In addition, the antioxidant assays indicated that FMBP-1 possessed certain capacities for scavenging free radicals and reducing power, and this was in a concentration-dependent manner. This research will provide fundamental data regarding the structure–activity relationship of millet bran polysaccharides and provide a theoretical foundation for the high-value utilization of millet bran within the food and pharmaceutical industries.

Spray cooling, of which the essence is droplet impacting, is an efficient thermal management technique for dense electronic components in unmanned aerial vehicles (UAVs). Nanofluids are pointed as promising cooling dispersions. Since the nanofluids are unstable, a dispersant could be added to the fluid. However, the added dispersant may influence the droplet, thereby impacting behaviors. In this work, the effects of dispersant on the nanofluid droplet-impacting dynamics are studied experimentally. The base fluid is deionized water (DI water), and Al2O3 is the selected nanoparticle. Sodium dodecyl sulfate (SDS) is used as the dispersant. Five different concentrations of nanofluids are configured using a two-step method. Droplet impacting behaviors are observed by high-speed imaging techniques. The other effects, i.e., the nanofluid particle volume fraction and the Weber number on droplet impact dynamics, are also systematically investigated. The results illustrate that the surface tension of the Al2O3 nanofluid increases with increased nanofluid concentrations. The surface tension of Al2O3 nanofluid with SDS is lower than that of DI water. And the increase in droplet impact velocity increases the spreading morphology. Nanofluid droplets exhibit spreading and equilibrium process when SDS is added. Furthermore, as the concentration of the nanofluid increases, the spreading process is inhibited. Whereas without SDS, the droplets undergo spreading, receding, and equilibrium processes. Moreover, there is no appreciable change in the impacting process with concentration increase. The empirical models of maximum spreading factor should be established without SDS and with SDS, respectively. This study can provide theoretical basis and specific guidance for experimental characterization of UAVs’ electronic devices based on the mechanism of nanofluid droplet impact on the wall.

The extraction of buildings from synthetic aperture radar (SAR) images poses a challenging task in the realm of remote sensing (RS). In recent years, convolutional neural networks (CNNs) have rapidly advanced and found application in the field of RS. Researchers have investigated the potential of CNNs for the semantic segmentation of SAR images, bringing excellent improvements. However, the semantic segmentation of buildings in SAR images still encounters challenges due to the high similarity between features of ground objects and buildings in SAR images, as well as the variability in building structures. In this article, we propose the local–global multiscale fusion network (LGMFNet), based on a dual encoder–decoder structure, for the semantic segmentation of buildings in SAR images. The proposed LGMFNet introduces an auxiliary encoder with a transformer structure to address the limitation of using the main encoder with a CNN structure for global modeling. To embed global dependencies hierarchically into the CNN, we designed the global–local semantic aggregation module (GLSM). The GLSM serves as a bridge between the dual encoders to achieve semantic guidance and coupling from the local to the global level. Furthermore, to bridge the semantic gap between different scales, we designed the multiscale feature fusion network (MSFN) as the decoder. MSFN achieves the interactive fusion of semantic information between various scales by constructing the multiscale feature fusion module. Experimental results demonstrate that the proposed LGMFNet achieves the mIoU of 91.17% on the BIGSARDATA 2023 AISAR competition dataset, outperforming the second-best method by a margin of 0.78%. This evidences the superiority of LGMFNet in comparison to other state-of-the-art methods.

The FengYun-3E (FY-3E) satellite was successfully launched on 5 July 2021. It is a polar-orbiting meteorological satellite and the world's first civilian morning and night orbit meteorological satellite. It carries a medium-resolution spectral imager-LL payload that delivers high-resolution outgoing longwave radiation (OLR) products. OLR can reflect more atmospheric change information, is more sensitive to temperature change, and can better reflect the entire surface atmospheric system, which is conducive to the in-depth understanding of the seismic sphere coupling module. OLR is widely used in seismic infrared anomaly extraction. The additive tectonic stress from the celestial tide-generating force (ATSCTF) seismic anomaly extraction algorithm has been continuously improved. However, the threshold of seismic thermal anomaly is mostly based on experience. The results of the quartile algorithm are objective, and it has some advantages in recognizing abnormal values. Whether the FY-3E can be used for seismic risk monitoring remains to be investigated. In this study, the 2023 Türkiye double earthquakes are taken as an example; the seismic anomalies of FY-3E OLR data are extracted based on the ATSCTF algorithm, and the anomaly threshold is determined via the quartile method. The results show that the ATSCTF algorithm based on the quartile threshold method is suitable for FY-3E data, and FY-3E OLR data have a certain response to pre-earthquake radiation anomalies, which can be used for seismic infrared anomaly tracking. The comprehensive use of ascending and descending data can better serve the extraction of seismic anomalies. High-resolution temporal remote sensing data are more conducive to the extraction of seismic anomalies via ATSCTF. The research and practice of seismic risk monitoring based on the ATSCTF algorithm can be further strengthened.

Poplar is a tree species used in urban greening, and colored leaf poplar is in great demand because of its higher ornamental value and function. In this study, we generated a golden leaf 84 K poplar (Populus alba × Populus glandulosa) by overexpressing the AtSep2 (stress-enhanced protein) gene from Arabidopsis. AtSep2 belongs to the light-harvesting chlorophyll (Chl)-binding complex (LHC)-like family and contains a conserved Chl-binding motif. Subcellular localization analysis showed that AtSep2 was mainly localized in the chloroplasts of poplar leaves. AtSep2 overexpression caused the golden leaf phenotype in poplar by reducing total Chl content. Before and after high light stress, the relative reduction in total Chl content and maximum quantum yield of PSII photochemistry (Fv/Fm) in transgenic poplar leaves was lower than that in wild-type (WT) leaves. Transgenic poplar leaves accumulated less reactive oxygen species (ROS) and had a higher net photosynthetic rate (Pn) than WT leaves under high light stress. Overall, AtSep2 overexpression caused the golden leaf phenotype and enhanced the tolerance of poplar leaves to high light stress. The present study suggests that AtSep2 is ideal for the genetic improvement of the golden leaf phenotype in poplar and other ornamental plants.

Abstract Pyroptosis, a mode of inflammatory cell death, has recently gained significant attention. However, the underlying mechanism remains poorly understood. HGS-ETR1/2 is a humanized monoclonal antibody that can bind to DR4/5 on the cell membrane and induce cell apoptosis by activating the death receptor signalling pathway. In this study, by using morphological observation, fluorescence double staining, LDH release and immunoblot detection, we confirmed for the first time that HGS-ETR1/2 can induce GSDME-mediated pyroptosis in hepatocellular carcinoma cells. Our study found that both inhibition of the AKT signalling pathway and silencing of CPA4 promote pyroptosis, while the overexpression of CPA4 inhibits it. Furthermore, we identified a positive regulatory feedback loop is formed between CPA4 and AKT phosphorylation. Specifically, CPA4 modulates AKT phosphorylation by regulating the expression of the AKT phosphatase PP2A, while inhibition of the AKT signalling pathway leads to a decreased transcription and translation levels of CPA4. Our study reveals a novel mechanism of pyroptosis induced by HGS-ETR1/2, which may provide a crucial foundation for future investigations into cancer immunotherapy.

Summary: Hepatitis B virus (HBV) infection generally elicits weak type-I interferon (IFN) immune response in hepatocytes, covering the regulatory effect of IFN-stimulated genes. In this study, low level of IFN-stimulated gene 12a (ISG12a) predicted malignant transformation and poor prognosis of HBV-associated hepatocellular carcinoma (HCC), whereas high level of ISG12a indicated active NK cell phenotypes. ISG12a interacts with TRIM21 to inhibit the phosphorylation activation of protein kinase B (PKB, also known as AKT) and β-catenin, suppressing PD-L1 expression to block PD-1/PD-L1 signaling, thereby enhancing the anticancer effect of NK cells. The suppression of PD-1-deficient NK-92 cells on HBV-associated tumors was independent of ISG12a expression, whereas the anticancer effect of PD-1-expressed NK-92 cells on HBV-associated tumors was enhanced by ISG12a and treatments of atezolizumab and nivolumab. Thus, tumor intrinsic ISG12a promotes the anticancer effect of NK cells by regulating PD-1/PD-L1 signaling, presenting the significant role of innate immunity in defending against HBV-associated HCC.

Effectively converting greenhouse gas CO2 into value-added chemicals, without the need for cocatalysts or solvents, is a vital objective in order to attain carbon neutrality and promote sustainable development. However, achieving this goal continues to pose significant challenges. In this study, the in-situ formed octadentate N5O3 tripodal ligand (H3L) reacts with ZnBr2 and ZnI2 to produce two ionic-type zinc catalysts, [Zn2(L)]2[ZnBr4]·4CH3OH (IZ-1) and [Zn2(L)]I·CH3OH (IZ-2), respectively. In the [Zn2(L)] subunit, the two Zn ions exhibit non-symmetry and are coordinated with the N5O3 ligand in a five- and six-coordinate mode, respectively. Due to the coexistence of Lewis acidic Zn sites and nucleophilic Br- ions, IZ-1 shows remarkable catalytic performance in the cycloaddition of CO2 with epoxides. Under cocatalyst- and solvent-free conditions, it achieves an excellent yield of cyclic carbonates, reaching up to 99 %. The ionic-type zinc catalyst can be readily recovered and reused at least for five times without a noticeable loss in catalytic activity. Mechanistic investigation demonstrates that the improved activity of IZ-1 is attributed to the synergistic effect of Lewis acidic Zn centers and nucleophilic Br-. Moreover, the broad substrate scope of IZ-1 further highlights its versatility and applicability in the cycloaddition reaction.

ABSTRACT The absence of a hepatitis B virus (HBV) infection system has constrained the study of the viral life cycle and the development of antiviral drugs. We previously established a hepatocellular carcinoma cell line, HLCZ01, that can support the entire life cycle of HBV. To further optimize the model, we compared the kinetic process of HBV infection in HLCZ01 and HepG2-NTCP cells and found that HLCZ01 cells were more conducive to mimic the long-term stable infection of HBV in the natural state. By comparing the composition of the progeny virus and the differences in gene expression profiles between these two types of cells, we were able to explore the factors affecting the efficiency of virus infection. We built an experimental platform for human liver chimeric mice and established a standard surgical procedure. By transplanting HBV-infected HLCZ01 cells into mouse liver, which can be used instead of primary human hepatocytes to establish chimeric mice, this animal model can continuously produce viral particles. The establishment of these two models will facilitate the exploration of the mechanism of persistent HBV infection, the understanding of host‒virus interactions, and the determination of new targets for chronic hepatitis B therapy. IMPORTANCE Approximately 257 million people worldwide have been infected with hepatitis B virus (HBV), and HBV infection can cause chronic hepatitis, cirrhosis, and even liver cancer. The lack of suitable and effective infection models has greatly limited research in HBV-related fields for a long time, and it is still not possible to discover a method to completely and effectively remove the HBV genome. We have constructed a hepatocellular carcinoma cell line, HLCZ01, that can support the complete life cycle of HBV. This model can mimic the long-term stable infection of HBV in the natural state and can replace primary human hepatocytes for the development of human liver chimeric mice. This model will be a powerful tool for research in the field of HBV.

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8+ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8+ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1–6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8+ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8+ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti-PD1/PDL1 immunotherapies in HCC.

Summary: Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

This study aimed to screen out bacterial strains with higher lignocellulolytic degradation enzyme activity and explore the effect of this strain on the highland barely soluble dietary fiber content through fermentation. Soil samples were collected from the ground of Nanjing Agriculture University (Nanjing, China) and used for enrichment culture. The methods used to screen the bacteria with high lignocellulose-degrading ability included decolorization test of aniline blue, hydrolyzation circle measurement of sodium carboxymethyl cellulose, disintegration test of filter paper strip and detection of enzyme activity. Six bacteria were isolated with lignocellulose degrading ability, of which LM1-strain possessed high lignocellulose degrading ability. The LM1 strain was identified as Bacillus velezensis by morphological, physiological, biochemical characteristics and molecular sequence analysis. Antibiotic sensitivity tests and hemolysis tests showed that strain LM1 was sensitive to all antibiotics and caused no hemolysis, indicating the safety of strain LM1. Strain LM1 was used to ferment highland barley whole grain flour and the content of soluble dietary fiber reached high levels (12.57 g/100 g), which was 2.07 times that of the raw barley soluble dietary fiber (6.07 g/100 g). The purity of soluble dietary fiber also reached the level of enzymatic extraction. The results will enrich the types of fermentation strains and promote the development and utilization of cereals and their by-products.

ABSTRACT KDM7A (lysine demethylase 7A, also known as JHDM1D) is a histone demethylase, it is mainly involved in the intracellular post-translational modifications process. Recently, it has been proved that the histone demethylase members can regulate the replication of hepatitis B virus (HBV) and the expression of key molecules in the Janus-activated kinase-signal transducer and activator of the transcription (JAK/STAT) signaling pathway by chromatin modifying mechanisms. In our study, we identify novel roles of KDM7A in HBV replication and immune microenvironment through two subjects: pathogen and host. On the one hand, KDM7A is highly expressed in HBV-infected cells and promotes HBV replication in vitro and in vivo. Moreover, KDM7A interacts with HBV covalently closed circular DNA and augments the activity of the HBV core promoter. On the other hand, KDM7A can remodel the immune microenvironment. It inhibits the expression of interferon-stimulated genes (ISGs) through the IFN-γ/JAK2/STAT1 signaling pathway in both hepatocytes and macrophages. Further study shows that KDM7A interacts with JAK2 and STAT1 and affects their methylation. In general, we demonstrate the dual functions of KDM7A in HBV replication and immune microenvironment, and then we propose a new therapeutic target for HBV infection and immunotherapy. IMPORTANCE Histone lysine demethylase KDM7A can interact with covalently closed circular DNA and promote the replication of hepatitis B virus (HBV). The IFN-γ/JAK2/STAT1 signaling pathway in macrophages and hepatocytes is also downregulated by KDM7A. This study provides new insights into the mechanism of HBV infection and the remodeling of the immune microenvironment.

Objective: This paper mainly studied the effects and regulation of exogenous addition of pyruvate, overexpression of pyruvate kinase and acetyl-CoA synthase on the synthesis of Bacillomycin D. Methods: In this study, B. amyloliquefaciens fmbJ was used as the initial strain. Firstly, the effect of exogenous pyruvate with different concentrations on the yield of Bacillomycin D was detected by HPLC. The regulation of pyruvate in this process was detected by RT-PCR. Then, pyruvate kinase (pyk) and acetyl-CoA synthase (acs) overexpression strains B. amyloliquefaciens fmbJ-pyk and fmbJ-acs were constructed by electrotransformation, and their Bacillomycin D production induced by different concentrations of IPTG was studied. Results: 0.075% pyruvate could increase the yield on Bacillomycin D to 1.41-fold that of the control group. The upregulation of Bacillomycin D synthesis gene also verified this enhancement. In addition, pyruvate could up-regulate the expression of regulatory factors such as comA, comP, comQ, sigH, sigM, degU, degQ, spo0A and codY, down-regulate the expression of rapC and abrB, promote the production of acetyl CoA synthase, and finally jointly promote the synthesis of Bacillomycin D. Under the induction of 50 mg/L IPTG, the yield of Bacillomycin D of fmbJ-acs and fmbJ-pyk increased to 1.16-fold and 1.34-fold that of fmbJ, respectively. Conclusion: This study found that exogenous addition of pyruvate and overexpression of acs or pyk could promote the synthesis of Bacillomycin D, clarified the regulation of pyruvate in the synthesis of Bacillomycin D, and widened a new research idea for promoting the efficient production of Bacillomycin D.

IL-6 and RasGRP1 have been shown to have important functions during inflammation and cancer. Here the authors propose the protein and mRNA of RasGRP1 have opposing functions by promoting IL-6 mediated acute inflammation and inhibiting inflammation-associated cancer through mRNA and protein mechanisms respectively.

Objectives: This study aimed to reveal the 30-year dynamics of hepatitis B virus (HBV) and hepatitis C virus (HCV) disease burden in China from 1990-2019. Methods: HBV/HCV data were retrieved from the Global Burden of Disease database. Joinpoint regression was used to examine temporal trends. Age-period-cohort models were applied to evaluate effects of patient age, period, and cohort on HBV/HCV-associated mortality and incidences. Results: A dramatic decrease in the disease burden of HBV was found from 1990-2019, but the disease burden of HCV has remained stable since 2000. Patient age, period, and cohort exerted a significant effect on the diseases burden of HBV and HCV infection. Compared with women, men had a higher risk of HBV/HCV infections as well as HBV/HCV-associated mortality and liver cancer. Overweight, alcohol, tobacco, and drug use were important risk factors associated with HBV/HCV-associated liver cancer. The incidences of HBV- and HCV-associated liver cancer from 2019-2044 are expected to decrease by 39.4% and 33.3%, respectively. Conclusion: The disease burden of HBV/HCV infection has decreased in China over the past 30 years, but HBV incidences remain high, especially in men. Effective management of HBV and HCV infections is still needed for high-risk populations.

Objectives An updated epidemiological analysis of gastrointestinal stromal tumour (GIST), the change of cancer-specific survival (CSS) and patterns of initial treatment are of interest.Design A retrospective study using data from the Surveillance, Epidemiology and End Results (SEER) database.Setting and participants A total of 5625 patients with GIST diagnosed between 2010 and 2019 were identified.Primary outcome measures Age-standardised incidence rate (ASIR) and annual prevalence rate were calculated. SEER combined stage, period CSS rate and initial treatment were summarised. All the data were calculated by SEER*Stat software.Results From 2010 to 2019, the ASIR of GIST increased from 0.79 to 1.02 per 100 000 person-years, with an increase of 2.4% annually. The increase was across age and sex subgroups. The prevalence trend was similar with the ASIR trend in each subgroup. The stage distributions were similar between different age groups, but varied among different primary tumour sites. More importantly, a stage shift from regional stage to localized stage at diagnosis was found, which may result in the improvement of CSS over years. Overall, the 5-year CSS rate of GIST was approximately 81.3%. Even for metastatic GIST, the rate exceeded 50%. Surgery was the most common treatment regimen for GIST, followed by surgery and systemic treatment. Whereas approximately 7.0% patients were undertreated, which was more pronounced among patients with distant and unknown stages.Conclusions The findings of this study suggest an improving early detection of GIST and an improving ability of accurate staging. Though most patients are effectively treated and perform good survivals, approximate 7.0% patients may be undertreated.

The host always employs various ways to defend against viral infection and spread. However, viruses have evolved their own effective strategies, such as inhibition of RNA translation of the antiviral effectors, to destroy the host's defense barriers. Protein synthesis, commonly controlled by the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), is a basic cellular biological process among all species. In response to viral infection, in addition to inducing the transcription of antiviral cytokines by innate immunity, infected cells also inhibit the RNA translation of antiviral factors by activating the protein kinase R (PKR)-eIF2α signaling pathway. Regulation of innate immunity has been well studied; however, regulation of the PKR-eIF2α signaling pathway remains unclear. In this study, we found that the E3 ligase TRIM21 negatively regulates the PKR-eIF2α signaling pathway. Mechanistically, TRIM21 interacts with the PKR phosphatase PP1α and promotes K6-linked polyubiquitination of PP1α. Ubiquitinated PP1α augments its interaction with PKR, causing PKR dephosphorylation and subsequent translational inhibition release. Furthermore, TRIM21 can constitutively restrict viral infection by reversing PKR-dependent translational inhibition of various previously known and unknown antiviral factors. Our study highlights a previously undiscovered role of TRIM21 in regulating translation, which will provide new insights into the host antiviral response and novel targets for the treatment of translation-associated diseases in the clinic.

Here the authors show that the Koolen-de Vries syndrome associated gene KANSL1 modulates autophagosome-lysosome fusion via transcriptional regulation of autophagosomal gene Syntaxin17, and that 13-cis retinoic acid can reverses mitophagic defects and neurobehavioural abnormalities of mice lacking Kansl1.

Abstract Introduction The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of perineural versus intravenous dexamethasone on interscalene block for pain control after shoulder arthroscopy. Methods We have searched PubMed, Embase, Web of science, EBSCO and Cochrane library databases through April 2021 and included randomized controlled trials (RCTs) assessing the effect of perineural and intravenous dexamethasone on interscalene block in patients with shoulder arthroscopy. Results Five RCTs were included in the meta-analysis. Overall, compared with intravenous dexamethasone for shoulder arthroscopy, perineural dexamethasone led to similar block duration (SMD = 0.12; 95% CI − 0.12 to 0.35; P = 0.33), pain scores at 12 h (SMD = − 0.67; 95% CI − 1.48 to 0.15; P = 0.11), pain scores at 24 h (SMD = − 0.33; 95% CI − 0.79 to 0.14; P = 0.17), opioid consumption (SMD = 0.01; 95% CI − 0.18 to 0.19; P = 0.95) and incidence of nausea/vomiting (OR = 0.74; 95% CI 0.38–1.44; P = 0.38). Conclusions Perineural and intravenous dexamethasone demonstrated comparable pain relief after shoulder arthroscopy.

A new analytical solution for the thermal-hydraulic coupling process is derived with a 1-D steady state conductive heat flow in the body of hot rock with perpendicular water flow in the single fracture and transient heat transfer from rock to water. The heat produced from the hot rock via water flow in the idealized single fracture is demonstrated by arithmetic equations. The applicability of the analytical solution is verified by numerical calculations and is limited to conditions with fast water flow rates or high water flux and long fluid pathways. The lifetime of an EGS reservoir in these reference conditions is 23.2 years and is confined by the produced water temperature of 150 °C for commercial utilization. The heat recovery factor is 12.4%. With a power plant capacity of 5 Mw installed, the total area for extracting recoverable heat within the projected lifetime of a fracture surface of 1.58 × 106 m2 was determined. The total mass flow rate of water injected into the large fracture was 57 kg/s. The discussion shows the ability of the model to estimate heat production and reservoir scale.

Background & Aims: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV), existing as a stable minichromosome in the hepatocyte, is responsible for persistent HBV infection. Maintenance and sustained replication of cccDNA require its interaction with both viral and host proteins. However, the cccDNA-interacting host factors that limit HBV replication remain elusive. Methods: Minicircle HBV (MC-HBV), a recombinant cccDNA, was constructed based on chimeric intron and minicircle DNA technology. By mass spectrometry based on pull-down with biotinylated MC-HBV, the cccDNA-hepatocyte interaction profile was mapped. HBV replication was assessed in different cell models that support cccDNA formation. Results: MC-HBV supports persistent HBV replication and mimics the cccDNA minichromosome. The MC-HBV–based screen identified cohesin complex as a cccDNA binding host factor, leading to reduced HBV replication. Mechanistically, with the help of CCCTC-binding factor (CTCF), which has specific binding sites on cccDNA, cohesin loads on cccDNA and reshapes cccDNA confirmation to prevent RNA polymerase II enrichment. Interestingly, HBV X protein transcriptionally reduces structural maintenance of chromosomes complex expression to partially relieve the inhibitory role of the cohesin complex on HBV replication. Conclusions: Our data not only provide a feasible approach to explore cccDNA-binding factors, but also identify cohesin/CTCF complex as a critical host restriction factor for cccDNA-driven HBV replication. These findings provide a novel insight into cccDNA–host interaction and targeted therapeutic intervention for HBV infection.

Cuticular wax plays an important role in plant drought tolerance by limiting non-stomatal water loss and has a diverse micromorphology and composition. However, the contribution of different wax components to limiting non-stomatal water loss remains unclear. We investigated and compared the micromorphology of cuticular wax on the leaves of five Dianthus plants and its role in limiting non-stomatal water loss. Furthermore, we further analyzed the chemical components of the cuticular waxes. Our results showed that cuticular wax crystals on the leaves of five Dianthus plants were mainly composed of irregular platelets or tubular epicuticular wax. The deposition of tubular wax may be related to better limiting non-stomatal water loss than platelets wax in the leaves of five Dianthus plants. Chemical component analysis revealed that the tubular wax was mainly composed of tricosane-2,4-dione. Our study suggests that tubular wax composition is an important trait for limiting non-stomatal water loss in several Dianthus species and contributes to the improvement of drought tolerance in other Dianthus plants.

In this study, the rheological properties and physical significations of an incompressible viscoelastic (inCVE) the inCVE model was investigated by employing molecular dynamics calculations. Polypropylene (PP) and polystyrene (PS) polymers were selected as candidate materials, the corresponding cell models consisting of five chains of 80 (PP) and 30 (PS) units were built successively. The energy minimization and anneal treatment were launched to optimize the unfavorable structures. The periodic boundary condition, COMPASS force field and the Velocity-Verlet algorithm were employed to calculate the shear flow behavior of chains. The sample data were collected and fitted based on the Matlab platform, and the analysis of the variance (ANOVA) method was performed to determine the validity of the model. Experimental results reveal that the inCVE model matches well with the pseudo-plastic fluids. Compared with the Ostwald-de Waele power law model and Cross model, it is effective and robust, and exhibits a three-stage rheological characteristic. Moreover, it characterizes the stress yield, activation energy, temperature dependence and viscoelastic response of polymers.

Phytoextraction in phytoremediation is one of the environmentally friendly methods used for restoring soils contaminated by heavy metals (HMs). The screening and identification of HM-resistant plants and their regulatory genes associated with HM ion transport are the key research aims in this field. In this study, a plant cadmium (Cd) resistance (PCR) gene family member, SlPCR6, was identified in roots of Salix linearistipularis, which exhibits strong HM resistance. The results revealed that SlPCR6 expression was induced in S. linearistipularis roots in response to Cd stress. Furthermore, SlPCR6 was mainly localized on the plasma membrane. Compared with the wild type, SlPCR6 overexpression reduced the Cd and copper (Cu) contents in the transgenic poplar (84 K) and increased its Cd and Cu resistance. The roots of transgenic poplar seedlings had lower net Cd and Cu uptake rates than wild type roots. Further investigation revealed that the transcript levels of multiple HM ion transporters were not significantly different between the roots of the wild type and those of the transgenic poplar. These results suggest that SlPCR6 is directly involved in Cd and Cu transport in S. linearistipularis roots. Therefore, SlPCR6 can serve as a candidate gene to improve the phytoextraction of the HMs Cd and Cu through genetic engineering.

Bacterial lipoproteins perform a diverse array of functions including bacterial envelope biogenesis and microbe-host interactions. Lipoproteins in gram-negative bacteria are sorted to the outer membrane (OM) via the localization of lipoproteins (Lol) export pathway. The ATP-binding cassette (ABC) transporter LolCDE initiates the Lol pathway by selectively extracting and transporting lipoproteins for trafficking. Here, we report cryo-EM structures of LolCDE in apo, lipoprotein-bound, and AMPPNP-bound states at a resolution of 3.5 to 4.2 Å. Structure-based disulfide crosslinking, photo-crosslinking, and functional complementation assay verify the apo-state structure and reveal the molecular details regarding substrate selectivity and substrate entry route. Our studies snapshot 3 functional states of LolCDE in a transport cycle, providing deep insights into the mechanisms that underlie LolCDE-mediated lipoprotein sorting in E. coli.

Under the background of promoting the construction of ecological civilization and the goal of carbon peak and carbon neutralization, it is of great significance to explore the measurement method and improvement strategy of the carbon effect of agricultural land consolidation. Based on a quantitative analysis and the whole life cycle of land consolidation, this study constructed a carbon effect accounting and analysis framework of agricultural land consolidation project from three stages of project initiation and design, project implementation, and operation management. Taking the agricultural land consolidation project in the Shiyan town on the urban edge of the Three Gorges Reservoir Area as a case, this study made empirical analysis and calculation and analyzed the carbon effect and influencing factors in different consolidation stages. The results showed that the overall carbon effect in the project area was a carbon source. The net carbon emission generated by the project construction was 8358t, which was mainly from workers input and concrete carbon emission; the carbon storage brought about by the adjustment of land use structure was 2,378.20t, which mainly came from the carbon storage increment of newly cultivated land; the carbon storage generated by the agricultural ecosystem was 1,100.04t, which was mainly based on the increase of cultivated land and the improvement of cultivated land quality; the carbon emission from agricultural production activities was 18.18t. Research conclusions: ① the carbon source effect of engineering construction is obvious. Artificial input and concrete are the main carbon sources in the hilly area at the edge of the metropolis; ② the adjustment of land use structure is manifested as a carbon sink effect, which mainly comes from the contribution of carbon storage of newly increased cultivated land; ③ the carbon effect of project operation and management may be a carbon source in the short term, and the long-term effect should be exerted; and ④ based on the concept of whole life cycle, promoting ecological land consolidation, optimizing project design, reasonably arranging consolidation projects, and strengthening operation management are effective measures to improve the carbon effect of land consolidation projects, which are conducive to the realization of the “double carbon” goal.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor clinical outcomes, and the infection of hepatitis B virus (HBV) is the leading cause of this disease. Mounting evidence shows that RNA binding proteins (RBPs) can modulate the progression of cancers. However, the functions and clinical implications of RBP-related mRNAs in HBV-related HCC remain largely unclear. Therefore, we aim to develop a prognostic model based on the RBP-related mRNAs for HBV-related HCC patients. Firstly, we identified 626 differentially expressed RBP-related mRNAs in the HBV-related HCC through the Pearson correlation analysis. Subsequently, the Kaplan-Meier survival, univariate, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses were used to construct a prognostic model comprised of five RBP-related mRNAs. Furthermore, the patients were categorized into the high- and low-risk groups by the prognostic model and the patients in the high-risk group had a poor prognosis. Additionally, the prognostic model was an independent predictor of prognosis, and the accuracy of the prognostic model was proved by the receiver operator characteristic (ROC) analysis. Furthermore, the functional enrichment analysis revealed that various cancer-promoting processes were enriched in the high-risk group. Taken together, our study may provide the HBV-related HCC biomarkers of prognosis to improve the clinical outcomes of patients.

ObjectiveThis study aims to reveal epidemiological features and trends of liver cancer (LC) in China.MethodsWe retrieved data from the Global Burden of Disease database 2019. Joinpoint regression was used to examine the temporal trend of LC. Future trends of LC were estimated using the Nordpred.ResultsThe incidence, mortality, and disability-standardized life year (DALY) rate of LC declined in China from 1990 to 2019. Among >210,000 LC cases in 2019, the LC incidences were nearly 3.15 times higher in males than in females. LC cases and LC-associated deaths were mostly found among patients aged 65 to 69 years. The proportion of LC attributable to hepatitis B decreased over time, whereas the proportions of LC attributable to hepatitis C, alcohol use, and non-alcoholic steatohepatitis increased modestly from 1990 to 2019. The majority of LC-associated deaths could be traced to four risk factors: smoking (20%), drug use (13.6%), alcohol use (11.7%), and high body mass index (10.1%). Based on the Nordpred prediction, there will be a steady decline in the incidence (39.0%) and mortality (38.3%) of liver cancer over a 25-year period from 2020 to 2044.ConclusionThe disease burden of liver cancer in China has declined over the past 30 years. However, it remains important to control liver cancer among high-risk populations, especially elderly males with obesity, alcohol use, tobacco use, and/or drug abuse.

BackgroundExposure to radiation is related to breast cancer occurrence. While whether the radioiodine (RAI) increases the risk of second breast cancer (SBC) in female differentiated thyroid cancer (DTC) patients is not well addressed.MethodsAll patients were identified from Surveillance, Epidemiology, and End Results database. At least a 5-year latency was guaranteed since exposure to RAI. Fine and Gray model was used to calculate the cumulative incidence and hazards ratios (HR) and 95% confidence interval (CI). Standardized incidence ratio (SIR) was calculated by Poisson regression analysis. Propensity score matching was used for match analysis. Survival analyses were performed by the Kaplan-Meier method and the log-rank test.ResultsA total of 406 out of 16,850 patients in the RAI group and 733 out of 22,135 patients in the no RAI group developed SBC. The cumulative incidences of SBC were higher in patients with RAI compared with patients without RAI in the adolescent and young adult (AYA) group and the middle-aged adult group. In the AYA group, patients with RAI had increased HR (1.65; 95% CI, 1.33–2.05, p

The sustainable development of a shallow aquifer geothermal reservoir is strongly affected by the reinjection–production strategy. However, the reinjection–production strategy optimization of a small-scale exploitation unit with tens of meters of well spacing is site specific and has not yet been fulfilled. This study numerically investigates sustainable heat extraction based on various reinjection–production strategies which were conducted in a single-phase aquitard–aquifer geothermal system in Huailai County, Hebei Province, China. The response of the water level and production temperature is mainly discussed. The numerical results show that production without reinjection induces the highest production temperature and also the water level drawdown. Although reinjection in a single doublet well system is conducive to the control of water level drawdown, the introduction of the thermal breakthrough problem causes a decrease in the production temperature. The thermal breakthrough and sustainability of geothermal reservoirs highly depend on the well spacing between the production and reinjection wells, especially for the small-scale field. Therefore, a large well spacing is suggested. A multi-well system facilitates the control of water level drawdown while bringing intensive well interference and thermal breakthrough. Large spacing between the production and reinjection wells is also the basic principle for the design of the multi-well system. A decrease in openhole length leads to an increase in the production temperature and output thermal power. An increase in the production rate affects the thermal breakthrough highly and shortens the lifetime of the geothermal system. Furthermore, the extracted thermal energy is highly affected by the reduction in the reinjection temperature. The results in this study can provide references to achieve sustainable geothermal exploitation in small-scale geothermal reservoirs.

The gene encoding a putative phosphatidate phosphatase (PAP) from tolerant saline-alkali (TSA) Chlorella, ChPAP, was identified from a yeast cDNA library constructed from TSA Chlorella after a NaCl treatment. ChPAP expressed in yeast enhanced its tolerance to NaCl and sorbitol. The ChPAP protein from a GFP-tagged construct localized to the plasma membrane and the lumen of vacuoles. The relative transcript levels of ChPAP in Chlorella cells were strongly induced by NaCl and sorbitol as assessed by northern blot analyses. Thus, ChPAP may play important roles in promoting Na-ion movement into the cell and maintaining the cytoplasmic ion balance. In addition, ChPAP may catalyze diacylglycerol pyrophosphate to phosphatidate in vacuoles.

To achieve efficient and accurate remaining life prediction and effectively express the uncertainty of prediction results, this paper proposes a remaining life prediction method based on fuzzy evaluation-Gaussian process regression (FE-GPR). First, the prediction of the remaining useful life (RUL) is affected by unknown variables, such as the environment, and it is difficult to achieve accurate predictions. It is necessary to effectively express the uncertainty of such prediction results. In this paper, we have put forward a RUL prediction method based on GPR, which can realize the RUL prediction with a confidence interval. Second, combined with the characteristics of the GPR method, an observation data preprocessing method based on fuzzy evaluation is proposed. The initial fuzzy evaluation method is established based on expert knowledge. Then, the classification nodes are optimized by the gravitational search algorithm (GSA) and historical data. This method, which uses fuzzy logic combined with expert knowledge, can avoid over-fitting in the case of limited data, and effectively improves the prediction accuracy of the GPR model. Finally, we use NASA PCoE. lithium battery data for a case study. The results show that the FE-GPR method achieves a more accurate RUL prediction and effectively reflects the uncertainty of the prediction results.

Abstract Pancreatic cancer (PC) is a highly malignant tumor with increased morbidity and mortality, which is difficult to diagnose and cure in the clinic. Through secreting exosomes containing biological molecules, including diverse RNAs and proteins, bone marrow mesenchymal stem cells (BM‐MSCs) influence the immunity, inflammation, tumor environment, and cancer metastasis. In this study, low expression of miRNA‐1231 (miR‐1231) in exosomes derived from the peripheral blood was significantly correlated with the TNM stage of PC, suggesting the potential inhibitory effect of exosomal miR‐1231 on PC occurrence and development. The proliferation, migration, invasion, and adhesion to the matrix of PC cells BxPC‐3 and PANC‐1 were negatively regulated by exosomes derived from the supernatants of BM‐MSCs that transfected with miR‐1231 oligonucleotides. Simultaneously, tumor growth in vivo was seriously restrained in BALB/C nude mice by tail vein injection with exosomes originated from BM‐MSCs that transfected with miR‐1231 mimics. The exosomes extracted from BM‐MSCs with high level of miR‐1231 inhibit the activity of PC, providing the potential application for developing new and efficient medicine for cancer therapy, especially for PC treatment. The exosomal miR‐1231 of peripheral blood may also be a potential indicator for PC diagnosis in the future.

To extend the application range of L-asparaginase in food pre-processing, the thermostability improvement of the enzyme is essential. Herein, two non-conserved cysteine residues with easily oxidized free sulfhydryl groups, Cys8 and Cys283, of Acinetobacter soli L-asparaginase (AsA) were screened out via consensus design. After saturation mutagenesis and combinatorial mutation, the mutant C8Y/C283Q with highly improved thermostability was obtained with a half-life of 361.6 min at 40 °C, an over 34-fold increase compared with that of the wild-type. Its melting temperature (Tm) value reaches 62.3 °C, which is 7.1 °C higher than that of the wild-type. Molecular dynamics simulation and structure analysis revealed the formation of new hydrogen bonds of Gln283 and the aromatic interaction of Tyr8 formed with adjacent residues, resulting in enhanced thermostability. The improvement in the thermostability of L-asparaginase could efficiently enhance its effect on acrylamide inhibition; the contents of acrylamide in potato chips were efficiently reduced by 86.50% after a mutant C8Y/C283Q treatment, which was significantly higher than the 59.05% reduction after the AsA wild-type treatment. In addition, the investigation of the mechanism behind the enhanced thermostability of AsA could further direct the modification of L-asparaginases for expanding their clinical and industrial applications.

Trans-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo. Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.

This paper considers the sequential fault diagnosis problem with unreliable tests which exist widely in practice. This problem involves real-time inference of the most likely set of failure sources, i.e., fault state, based on unreliable test outcomes. The purpose of this paper is to optimize test set and diagnostic strategy so as to cut down the test cost while isolating the fault accurately, and a method for optimal diagnosis strategy based on partially observable Markov decision process (POMDP) is presented. The components of the POMDP tailed to optimizing the diagnostic strategy are specified, and the solution to the POMDP-based model, namely the optimal strategy, is obtained to describe the optimal test sequence for fault diagnosis. The performance of the proposed method is evaluated with simulation experiments. All the results indicate that this method performs good in diagnostic efficiency and accuracy, even compared with the strategies of traditional methods.

Effects of chemical components on wood sorption property under dynamic condition were investigated for the first time. Hemicellulose, lignin and extractive (denoted as DHC, DL and DE, respectively) were removed from Populus euramericana Cv., 20 mm in radial (R) and tangential (T) directions with thickness of 4 mm along the grain, then the wood was subjected to cyclic tests where relative humidity (RH) varied from 45% to 75% sinusoidally at 25 °C. Based on measured data automatically, the results showed that, various chemical components had different effects on dynamic sorption behaviors of wood. The DL exhibited the largest moisture content and diffusion coefficient, followed by the DE, Control and DHC. This indicated lignin or extractive removal accelerated the dynamic sorption process and improved hygroscopicity of wood, while hemicellulose removal caused opposite effects. Theoretical sorption model was further applied and the modeled curves fitted satisfactorily with experimental data. Dynamic moisture gradient distribution inside the different treated wood was investigated and amplitude of moisture showed negative relation with wood element depth, while phase lag presented an opposite trend. Amplitude of DL was the largest while its phase lag was the least. Conditioning thickness for RH was greatest for DHC, about twice as much as the minimum of DL. Keywords: Chemical components removal, Dynamic cyclic relative humidity, Sorption, Conditioning property, Wood

Abstract Background Lipoxygenase (LOX) from Anabaena sp. PCC 7120 (Ana-rLOX) offers important applications in the food industry, especially for improving aroma and dough rheological properties. However, industrial applications of LOXs have been limited by their poor thermostability. Herein, we report a bioinformatics-based consensus concept approach for the engineering of thermostable Ana-rLOX. Results A series of mutations (N130D, G260A, S437T, N130D/G260Q, N130D/S437Y) showed higher thermostability and activity than the wild-type enzyme. Thus, N130D/G260Q exhibited a 6.6-fold increase in half-life and 2.45 °C increase in unfolding temperature; N130D/S437Y showed a 10 °C increase in optimal temperature. The secondary structure did not change much that contributed to improved thermostability were investigated in detail using circular dichroism. Homology modeling suggested that enhanced thermostability and specific activity may result from favorable hydrophobic interactions. Conclusions A series of mutations were achieved, showing higher thermostability and activity than the wild-type enzyme by semi-rational mutagenesis with limited structure information. Our findings provide important new insights into molecular modifications aimed at improving Ana-rLOX thermostability and activity.

Abstract Background Plipastatin, an antifungal lipopeptide, is synthesized by a non-ribosomal peptide synthetase (NRPS) in Bacillus subtilis. However, little information is available on the combinatorial biosynthesis strategies applied in plipastatin biosynthetic pathway. In this study, we applied module or individual domain deletion strategies to engineer the plipastatin biosynthetic pathway, and investigated the effect of deletions on the plipastatin assembly line, as well as revealed the synthetic patterns of novel lipopeptides. Results Module deletion inactivated the entire enzyme complex, whereas individual domain (A/T domain) deletion within module 7 truncated the assembly line, resulting in truncated linear hexapeptides (C16~17β-OHFA-Glu-Orn-Tyr-Thr-Glu-Ala/Val). Interestingly, within the module 6 catalytic unit, the effect of thiolation domain deletion differed from that of adenylation deletion. Absence of the T6-domain resulted in a nonproductive strain, whereas deletion of the A6-domain resulted in multiple assembly lines via module-skipping mechanism, generating three novel types of plipastatin derivatives, pentapeptides (C16~17β-OHFA-Glu-Orn-Tyr-Thr-Glu), hexapeptides (C16~17β-OHFA-Glu-Orn-Tyr-Thr-Glu-Ile), and octapeptides (C16~17β-OHFA-Glu-Orn-Tyr-Thr-Glu-Gln-Tyr-Ile). Conclusions Notably, a unique module-skipping process occurred following deletion of the A6-domain, which has not been previously reported for engineered NRPS systems. This finding provides new insight into the lipopeptides engineering. It is of significant importance for combinatorial approaches and should be taken into consideration in engineering non-ribosomal peptide biosynthetic pathways for generating novel lipopeptides.

L-asparaginase (E.C.3.5.1.1) is a well-known agent that prevents the formation of acrylamide both in the food industry and against childhood acute lymphoblastic leukemia in clinical settings. The disadvantages of L-asparaginase, which restrict its industrial application, include its narrow range of pH stability and low thermostability. In this study, a novel L-asparaginase from Mycobacterium gordonae (GmASNase) was cloned and expressed in Escherichia coli BL21 (DE3). GmASNase was found to be a tetramer with a monomeric size of 32 kDa, sharing only 32% structural identity with Helicobacter pylori L-asparaginases in the Protein Data Bank database. The purified GmASNase had the highest specific activity of 486.65 IU mg−1 at pH 9.0 and 50 °C. In addition, GmASNase possessed superior properties in terms of stability at a wide pH range of 5.0–11.0 and activity at temperatures below 40 °C. Moreover, GmASNase displayed high substrate specificity towards L-asparagine with Km, kcat, and kcat/Km values of 6.025 mM, 11,864.71 min−1 and 1969.25 mM−1min−1, respectively. To evaluate its ability to mitigate acrylamide, GmASNase was used to treat potato chips prior to frying, where the acrylamide content decreased by 65.09% compared with the untreated control. These results suggest that GmASNase is a potential candidate for applications in the food industry.

Deoxynivalenol (DON) is a widely distributed mycotoxin that frequently occurs in various agricultural raw materials and feeds. DON acts as a virulence factor that accelerates the spread of plant diseases; moreover, its accumulation in grains causes yield loss and serious health problems to humans and livestock. Biodegradation of DON into less- or non-toxic substances using naturally existing microorganisms is considered the best approach for DON detoxification. Although various single isolates and mixed cultures capable of detoxifying DON have been reported, details of the metabolic pathways and the degrading enzymes/coding genes involved are scarce. In this study, we aimed to isolate DON-degrading bacteria from soil samples and explore the mechanisms. Toward this end, 85 soil samples collected from different provinces in China were enriched under aerobic conditions with mineral media containing 50 μg/ml of DON as the sole carbon source. The bacterial consortium LZ-N1 exhibited highly efficient and steady DON-transforming activity. High-throughput sequencing was used to characterize the composition of the involved microflora, and analysis of 16S rRNA sequences indicated that LZ-N1 was composed of at least 11 bacterial genera, with Pseudomonas accounting for nearly half the relative abundance. Coincubation of a mixed culture of two novel strains from the LZ-N1 consortium, namely Pseudomonas sp. Y1 and Lysobacter sp. S1, showed sustained transformation of DON into the metabolite 3-epi-deoxynivalenol, with no degradation products detected after 72 h. The cell-free supernatant, lysate, and cell debris of the mixed culture possessed DON-degrading ability, with the supernatant reaching a DON degradation rate of 100% within 48 h with 50 μg/ml of DON. This is the first report of two-step enzymatic epimerization of DON by a mixed culture, which may provide a new insight into this pathway for future applications in detoxification of DON-contaminated cereals and feed.