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Water stability in acidic, neutral, and basic aqueous solutions is quite important for the potential application of metal–organic frameworks. As evidenced by X-ray diffraction and scanning electron microscopy results, the pristine DUT-4 is extremely water sensitive to acidic, neutral, and basic aqueous solutions and undergoes crystal structure and morphology transformation. The pristine DUT-4 nearly loses its porosity and H2 uptake capacity after being exposed for 6 d. A facile solution-immersion approach was employed to deposit a hydrophobic layer on the DUT-4 surface without significant loss of surface area. This layer could effectively protect DUT-4 from water molecule attack and greatly enhance water stability. After the same exposure to aqueous solutions, the hydrophobic-treated DUT-4 could basically retain their crystal structure, morphology, surface area, and H2 uptake capacity. This approach could be explored to broaden the scope of practical applications of DUT-4 and other metal–organic framework...

Plasmid-based microbial systems have been a major workhorse for chemical and pharmaceutical production. The biosafety issues and elevated industrial cost of antibiotic usage have led to the development of alternative strategies for plasmid selection and maintenance. Such strategies, including auxotrophy complementation, post-segregational killing, operator-repressor and RNA-based interactions often require extensive engineering of various elements and may result in extra metabolic burden in the cells. Herein, we report a design of synthetic symbiosis combining plasmid displacement to construct a phenotype-stable microbial system. By sequestrating an endogenous essential gene folP, cells obtained long-term plasmid maintenance with minimum cost. The phenotype performance was also inherited for up to 80 generations demonstrated by the production of salicylic acid in Escherichia coli. Meanwhile, the temperature-induced curing method of the intermediate plasmids enables rapid engineering. This design can lead to broad applications as a reliable and convenient plasmid-based expression system.

Microbial-based chemical synthesis serves as a promising approach for sustainable production of industrially important products. However, limited production performance caused by metabolic burden or genetic variations poses one of the major challenges in achieving an economically viable biomanufacturing process. To address this issue, one superior strategy is to couple the product synthesis with cellular growth, which renders production obligatory for cell survival. Here we create a pyruvate-driven metabolic scenario in engineered Escherichia coli for growth-coupled bioproduction, with which we demonstrate its application in boosting production of anthranilate and its derivatives. Deletion of a minimal set of endogenous pyruvate-releasing pathways engenders anthranilate synthesis as the salvage route for pyruvate generation to support cell growth, concomitant with simultaneous anthranilate production. Further introduction of native and non-native downstream pathways affords production enhancement of two anthranilate-derived high-value products including L-tryptophan and cis, cis-muconic acid from different carbon sources. The work reported here presents a new growth-coupled strategy with demonstrated feasibility for promoting microbial production.

Accumulating evidence suggests granulocyte macrophage-colony stimulating factor (GM-CSF) can function as an inflammatory mediator, but whether GM-CSF-producing CD4+ T cells (TH-GM-CSF) are a distinct T helper cell subset is lacking. Herein we demonstrate that interleukin (IL)-1β exclusively drives differentiation of naive CD4+ T cells into TH-GM-CSF cells via inducing ubiquitination of IL-1 receptor-associated kinase 1 (IRAK1) and subsequent activation of the transcription factor NF-kappaB (NF-κB), independent of RAR-related orphan receptor gamma (RORγt) required for TH17 differentiation. In vivo, TH-GM-CSF cells are present in murine Citrobacter Rodentium infections and mediate colitis following adoptive transfer of CD4+ T cells into Rag1−/− mice via GM-CSF-induced macrophage activation. The TH-GM-CSF cell phenotype is stable and distinct from the TH17 genetic program, but IL-1β can convert pre-formed TH17 cells into TH-GM-CSF cells, thereby accounting for previously reported associations between IL-17 and GM-CSF. Together, our results newly identify IL-1β/NF-κB-dependent TH-GM-CSF cells as a unique T helper cell subset and highlight the importance of CD4+ T cell-derived GM-CSF induced macrophage activation as a previously undescribed T cell effector mechanism.

Nitrogenous disinfection by-products (N-DBPs) in chlorinated drinking water are receiving increasing attention due to their elevated toxicities. An effective strategy to control the formation of N-DBPs is to reduce their nitrogenous precursors (e.g., amino acids [AAs], believed to be the important N-DBP precursors) before disinfection. So far, little information is available about the effectiveness of conventional microbial degradation at controlling the formation of N-DBPs. In this study, the biodegradability of 20 AAs was investigated, and the impacts of microbial degradation for the selected 6 typical AAs on the formation of N-DBPs (haloacetonitriles and haloacetamides) and traditional carbonaceous DBP (chloroform) were investigated. The results indicated that glycine, arginine, aspartic acid, asparagine, alanine and serine were susceptible to biodegradation, and the formation potentials (FPs) of DBPs were remarkably reduced after biodegradation. The highest chloroform FP reduction rates from tryptophan and tyrosine were 85.4% and 56.2%, respectively. The FPs of dichloroacetonitrile and trichloroacetamide were also reduced after biodegradation of the all selected AA samples during chlor(am)ination. Dichloroacetamide FPs decreased continuously with incubation time during chlorination for phenylalanine, asparagine, aspartic acid, and the mixed AAs, and the highest reduction rates were 78.7%, 74.6%, 46.7% and 35.3% respectively. The results of integrated toxicity analysis indicated that the pre-treatment of microbial degradation significantly decreased the integrated toxicity of DBPs formed from AAs. Moreover, the microbial community analysis revealed that Proteobacteria was predominant at phylum level in the mixed AA sample, and the dominant genera were Acinetobacter and Pseudomonas. Proteobacteria may play an important role in controlling DBP precursor.

This short note presents a new approach to estimate coefficients for gaseous jet loads at an inclined flat plate. These load coefficients are derived at the collisionless flow limit. The plate surf...

Duck hepatitis A virus (DHAV) is the major pathogen of duck viral hepatitis, which has caused great economic losses to duck breeding industry. As an effective delivery tool for protein antigens, Lactococcus lactis (L. lactis) has been successfully used to stimulate mucosal and systemic immune response. In this study, a recombinant L. lactis named NZ3900-VP1 was constructed, which could express VP1 protein of DHAV type 3 (DHAV-3) by using a nisin-controlled expression (NICE) system. The animal experiment in both mice and ducklings were performed to detect the immune response and protection effect of oral vaccination by the recombinant L. lactis. The results showed that oral vaccination with L. lactis NZ3900-VP1 significantly induced specific anti-VP1 IgG antibodies and mucosal secretory immunoglobulin A (sIgA) of DHAV-3 in mice and ducklings, and cytokines including interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-10 (IL-10) and interleukin-4 (IL-4). Notably, the ducklings vaccinated with L. lactis NZ3900-VP1 were effectively protected when facing natural infestation of DHAV-3, which indicated that the recombinant L. lactis could serve as an effective vaccine to prevent DHAV-3 infection in ducklings.

Rod-like porous composites of iron sulfides embedded in nitrogen-rich carbon have been synthesized through a simultaneous carbonization and sulfuration process of the Fe-based metal-organic framework (MIL-88) for the first time. The composites exhibit combined advantages of the porous structure, uniform distribution of iron sulfide nanoparticles and increased conductivity. As an anode material for lithium-ion batteries (LIBs), the composites show a high reversible capacity of 936.3 mAh g−1 after 300 cycles and an exceptional high-rate capability (1128, 1056, 989, 912, 841 mAh g−1 at the current densities of 0.1, 0.2, 0.4, 0.8, and 1.6 A g−1, respectively). The results indicate that the composites could be a promising candidate for anode materials in LIBs.

The aim of this study was to identify the novel missense eya4 mutation which cause autosomal dominant non syndromic hearing loss In a Chinese family. Hearing loss is the most common sensory deficit in humans, but the middle-frequency sensorineural hearing loss (MFSNHL) is rare among hereditary non-syndromic hearing loss, and EYA4 is one of the genes reported to be associated with MFSNHL. A genetic analysis of a Chinese family with autosomal dominant non"‘syndromic progressive hearing impairment was conducted and assessed. Targeted exome sequencing, conducted using DNA samples of an affected member in this family, revealed a novel heterozygous missense mutation c.1855T>G in exon 20 of EYA4, causing amino-acid (aa) substitution Gly for Trp at a conserved position aa-619. The p.W619G mutation related to hearing loss in this Chinese family was validated by Sanger sequencing. Bioinformatic analysis confirmed the pathogenic effects of this mutation. We identified the novel missense mutation c.1855T>G (p.W619G) in EYA4 causing autosomal dominant non-syndromic hearing impairment in the selected Chinese family.

Duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1) is an acute and highly contagious disease affecting young ducklings. The VP1 protein is one of the major structural proteins of DHAV-1 carries critical epitopes responsible for the induction of neutralizing antibodies. In this study, we have successfully constructed an immune phage display VHHs library against DHAV-1 with the size of 6 × 106 colonies. A nanobody (Nb) against VP1 protein of DHAV-1, named Nb25, was identified from the immunized phage display library. Nb25 could react with the conserved linear B-cell epitope of 174PAPTST179 in DHAV-1 VP1, even though Nb25 showed no neutralizing activity to DHAV-1. To the best of our knowledge, this is the first report about preparation of anti-DHAV-1 Nbs and identification of the specific conserved linear B-cell epitope of DHAV-1 with Nb, which will facilitate the serologic diagnosis of DHAV-1 infection.

Objective: Abnormal and dynamic epileptogenic networks cause difficulties for clinical epileptologists in the localization of the seizure onset zone (SOZ) and the epileptogenic zone (EZ) in preoperative assessments of patients with refractory epilepsy. The aim of this study is to investigate the characteristics of time-varying effective connectivity networks in various non-seizure and seizure periods, and to propose a quantitative approach for accurate localization of SOZ and EZ. Methods: We used electrocorticogram recordings in the temporal lobe and hippocampus from seven patients with temporal lobe epilepsy to characterize the effective connectivity dynamics at a high temporal resolution using the full-frequency adaptive directed transfer function (ffADTF) measure and five graph metrics, i.e., the out-degree (OD), closeness centrality (CC), betweenness centrality (BC), clustering coefficient (C), and local efficiency (LE). The ffADTF effective connectivity network was calculated and described in five frequency bands (δ, θ, α, β, and γ) and five seizure periods (pre-seizure, early seizure, mid-seizure, late seizure, and post-seizure). The cortical areas with high values of graph metrics in the transient seizure onset network were compared with the SOZ and EZ identified by clinical epileptologists and the results of epilepsy resection surgeries. Results: Origination and propagation of epileptic activity were observed in the high time resolution ffADTF effective connectivity network throughout the entire seizure period. The seizure-specific transient seizure onset ffADTF network that emerged at seizure onset time remained for approximately 20–50 ms with strong connections generated from both SOZ and EZ. The values of graph metrics in the SOZ and EZ were significantly larger than that in the other cortical areas. More cortical areas with the highest mean of graph metrics were the same as the clinically determined SOZ in the low-frequency δ and θ bands and in Engel Class I patients than in higher frequency α, β, and γ bands and in Engel Class II and III patients. The OD and C were more likely to localize the SOZ and EZ than CC, BC, and LE in the transient seizure onset network. Conclusion: The high temporal resolution ffADTF effective connectivity analysis combined with the graph theoretical analysis helps us to understand how epileptic activity is generated and propagated during the seizure period. The newly discovered seizure-specific transient seizure onset network could be an important biomarker and a promising tool for more precise localization of the SOZ and EZ in preoperative evaluations. peerReviewed

Natural products are promising chemicals due to their structural diversity and bioactivities. Over the decades, a vast variety of gene clusters encoding natural products have been identified and overexpressed in microbes. Recently, the development of metabolic engineering, synthetic biology and bioinformatics strategies have facilitated target discovery and design. Microbial cells have been therefore constantly engineered for product accumulation. This review summarizes approaches of domesticating microbial hosts in producing major classes of natural products, with an emphasis on recent advances.

The development of new aeronautics and astronautics technologies has been constrained by strict mathematical rules for data processing among the diverse methods used to obtain spatial information.The acquisition of spatial information has been affected by various choices including the applied technologies (e.g.,push broom sensors),techniques (e.g.,zoom imaging),and equipment settings (e.g.,swing angle,aerial platform attitude,camera angle) in terms of the convergence,efficiency,and accuracy of the data.Based on the principle of the bionic machine parallax angle and pyramidal projection of the aerial space platform to the surface,this study explored solutions for high-resolution image sparsity,ill-conditioned singularity,and non-convergence by building a set of mathematical models to process the polar coordinates of the parallax angular vector.This study also formed a polar information theory for initial spatial information.This method improved the ranges of accuracy,efficiency,and anti-interference in close-range photogrammetry and the free net bundle adjustment model by several orders of magnitude.The open source code was made globally available more than 3 years ago,and has received positive reactions.The method’s effectiveness was verified using aerophotogrammetry and absolute network adjustment model experiments,and its performance was better than that of the Cartesian coordinate processing method.Finally,the higher-order solution characteristics of various applications and spaceflight platforms were provided,which are expected to provide a foundation for construction of a new polar coordinate system for aerospace multi-scale all-attitude spatial information acquisition,organization,management,storage,processing,and application.

Novel duck reovirus (NDRV) causes high morbidity in ducklings, and recovered ducklings are often remarkably stunted in growth. In this study, four NDRV strains were isolated from the NDRV outbreaks that occurred in different regions of Shandong province, China. The biological characteristics and pathogenicity of the four NDRV strains were elucidated, and the N20 was identified as a naturally attenuated strain. Three-day-old ducklings were immunized with live N20 strain (100 ELD50/duck), and challenged with 104.52 ELD50 of virulent N19 strain at 7 days post immunization. The vaccinated ducklings showed no evidence of clinical signs, gross and histopathological lesions, or loss of body weight, and 100 % protection against the virulent NDRV N19 infection. The NDRV-specific antibodies were generated in the immunized ducklings and could neutralize different NDRV strains. These results indicated that the N20 strain was a promising live attenuated vaccine candidate against highly pathogenic NDRV infection.

Background: Ferroptosis is a newly described form of regulated cell death, targeting nuclear factor erythroid-2-related factor 2 (Nrf2) -mediated ferroptosis may be an attractive option to counteract malignant tumor. Whether miR-144-5p sensitize erastin-induced ferroptosis in gastric cancer via regulation of Nrf2 pathway is unclear. Methods: To speculate the function of miR-144-5p in cancers, bioinformatic analysis was performed. Dual-luciferase reporter gene assay was used to predict effect of miR-144-5p on the expression of Nrf2. The expressions of miR-144-5p and Nrf2 in human gastric cancer cell lines and tissues were detected by qPCR, Immunohistochemistry or western blot. Results: miR-144-5p, identified to wreck Nrf2 mRNA, was selected and overexpressed in gastric cancer cells to sensitize erastin-induced ferroptosis. Ectopic expression of miR-144-5p in AGS and BGC-823 cells downregulated the mRNA and protein expression of Nrf2. In addition, AGS and BGC-823 cell lines with exogenous expression of miR-144-5p were more sensitive to erastin-induced ferroptosis with overgeneration of lipid reactive oxygen species and depletion of glutathione. Conclusions: miR-144-5p sensitizes erastin-induced ferroptosis via abrogating expression of Nrf2 to eliminate cancer cells selectively with high Nrf2 pathway activation.

Background and Aims. There are few studies on the prevalence and clinical characteristics of portopulmonary hypertension (POPH) in patients with portal hypertension. In addition, invasive right heart catheterization further limits the clinical diagnosis of POPH patients. Methods. From January 2018 to December 2019, 1004 patients with portal hypertension were treated in the Department of Hepatology, the First Hospital of Jilin University. Based on the inclusion and exclusion criteria, 188 patients with portal hypertension were finally included. We collected complete clinical data, laboratory examinations, and imaging examinations. Patients were divided into a POPH group and a non-POPH group based on echocardiographic results. We calculated the prevalence of POPH in patients with portal hypertension. The differences in clinical characteristics of the two groups of patients were compared. Results. The prevalence of POPH in patients with portal hypertension was 2.8%. Among the 188 patients with portal hypertension with fingertip oxygen saturation < 95 % at rest, 28 patients had POPH (12 males and 16 females), with an average age of 63 ± 8 , and 160 patients did not have POPH (110 males, 50 women), with an average age of 59 ± 11 . The proportion of women in the POPH group ( P < 0.01 ) and patients without liver cancer ( P = 0.044 ) was high. Compared to patients without POPH, patients with POPH had lower hemoglobin (related to the severity of anemia, P < 0.01 ), higher creatinine ( P < 0.05 ), and lower partial pressure of oxygen and carbon dioxide ( P < 0.05 ). Patients with POPH had a higher incidence of atrial enlargement, ventricular enlargement, mitral valve regurgitation, tricuspid regurgitation, pulmonary artery widening, pericardial effusion, and aortic regurgitation than those without POPH. The risk of POPH did not increase with the aggravation of the Child-Pugh classification. Conclusion. The prevalence of POPH in patients with portal hypertension is 2.8%. The proportion of women and nonliver cancer in POPH patients was higher than that in non-POPH patients. In addition, the POPH group had higher creatinine and lower hemoglobin, and echocardiography showed that POPH patients had more cardiac structural changes. In patients with portal hypertension, the risk in patients with POPH has nothing to do with the Child-Pugh classification and MELD score.

BACKGROUND Balance dysfunction is common in adult outpatients with dizziness, especially those who are older, which can lead to catastrophic outcomes such as falls. The aim of this study was to investigate the association between chronic conditions and balance disorders in patients with dizziness, especially those who are elderly. MATERIAL AND METHODS A cross-sectional study was conducted in adult outpatients diagnosed with dizziness referred to the Department of Otolaryngology at Beijing Tongren Hospital from September 2017 to August 2018. All of the patients completed a self-administered, structured questionnaire. Demographic data and information on history of chronic conditions were collected and the patients were divided into 2 groups based on whether their balance was normal or abnormal. RESULTS Three hundred and thirty-two patients were included in this study, 168 in the normal balance group and 164 in the abnormal balance group. The incidence of chronic conditions, including hypertension and diabetes, in the abnormal balance group was higher than that in the normal balance group (all P0.05). In subgroup analysis based on age, in those who were aged ≥60 years, the prevalence of chronic diseases was higher in the abnormal balance group than in the normal balance group (P=0.002), while there was no difference in age between the groups with abnormal and normal balance. Hypertension (OR: 2.268; 95%CI: 1.038-4.957; P0.05) was a risk factor for balance disorders in elderly patients rather than those who were younger (P0.05). CONCLUSIONS Our results show that chronic conditions are associated with balance function in older patients with dizziness. Thus, specialists should consider chronic conditions, especially hypertension, in elderly patients with dizziness.

Panax notoginseng saponins (PNS), also called "sanqi" in Chinese, are the main active ingredients which are extracted from the root of Panax notoginseng (Burk.) F. H. Chen., and they have been traditionally used as a medicine in China for hundreds of years with magical medicinal value. PNS have varied biological functions, such as anti-inflammatory effects, anti-cancer effects, anti-neurotoxicity, and the prevention of diabetes. Nervous system disorders, a spectrum of diseases originating from the nervous system, have a significant impact on all aspects of patients' lives. Due to the dramatic gains in global life expectancy, the prevalence of nervous system disorders is growing gradually. Even if the mechanism of these diseases is still not clear, they are mainly characterized by neuronal dysfunction and neuronal death. Consequently, it is essential to find measures to slow down or prevent the onset of these diseases. At present, traditional Chinese medicines, as well as their active components, have gained widespread popularity in preventing and treating these diseases because of their merits, especially PNS. In this review, we predominantly address the recent advances in PNS researches and their biological functions, and highlight their applications in nervous system disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke.

The plasmid-borne fosfomycin resistance gene fosA3 has been identified in Escherichia coli (E. coli) from various animals but has rarely been reported in ducks. In this study, we investigated the fosA3 prevalence and molecular characteristics of fosA3-harboring E. coli strains from ducks in Shandong province of China. In 416 E. coli isolates, 91 (21.88%) were identified as fosA3-bearing strains, and the fosfomycin-resistant phenotype of 88 of the 91 fosA3-harboring strains was successfully transferred to the recipient strains. Seven different genetic structures surrounding the fosA3 gene were detected and two new contexts were discovered among the fosA3-carrying E. coli. Twenty fosA3-harboring isolates and their trans conjugants were randomly selected for pulsed-field gel electrophoresis (PFGE) typing and S1-nuclease PFGE, respectively. The PFGE patterns revealed that the 20 randomly selected fosA3-bearing isolates were not a result of clonal dissemination. S1-PFGE showed that 15 of the 20 randomly selected trans conjugants carried a single plasmid, and these 15 plasmids that harbored fosA3 (55–190 kb) were distributed into the following replicon types: IncF (n = 11), IncI1 (n = 1), IncN (n = 1), untypable (n = 1), and W-FIC (n = 1). Additionally, as vectors for fosA3 in E. coli, F-:A1:B6, N/ST1, IncI1/ST2, W-FIC, and one untypable plasmid had never been reported before. These observations highlighted the importance of ducks as a reservoir for multidrug-resistant fosA3-carrying E. coli.

The structure of Ironless Permanent Magnet Linear Synchronous Motors (IPMLSM) used in magnetic levitation is simple, however, the thrust increase is limited due to ironless. It is important to study how to increase the thrust of the motor. This paper uses two-dimensional finite element analysis method to calculate the thrust characteristics of different types of magnets. The thrust characteristics of IPMLSM with 2-segment Halbach magnet array, IPMLSM with improved 2-segment Halbach magnet array and IPMLSM with 4-segment Halbach magnet array are respectively calculated by simulation. Meanwhile, the influence of the mover magnets’ shape on the motor thrust characteristics is discussed.

Colon cancer is one of most common cancers. The progression of various cancers is driven by miRNA-570. The role of miRNA-570 in the progression of colon cancer remains unclear. We aimed to investigate the clinical function of miR-570 and its impact on colon cancer cells. We evaluated the expression of miR-570 in colon cancer cells and analyzed its influence on the various clinical parameters. The Kaplan-Meier curve was plotted to understand the clinical role of miR-570. Cox regression analysis was performed to predict the prognostic factors in colon cancer. The Cell Counting Kit-8 was used to investigate the effect of miR-570 on cell proliferation. The transwell migration assay was performed to quantify cell migration and invasion. The quantitative real-time polymerase chain reaction technique was used to analyze the sample system. The results revealed that the level of miR-570 expression in colon cancer tissues and cell lines was low. The abnormal expression of miR-570 was associated with tumor size, extent of differentiation, lymph node metastasis, and tumor-node-metastasis stages. Downregulation of miR-570 indicated poor overall survival (OS), poor relapse-free survival, and unfavorable cancer-specific survival (CSS) rates in patients with colon cancer. The results from Cox regression analysis revealed that miR-570 expression could be used as an independent prognostic biomarker for OS and CSS in colon cancer. Overexpression of miR-570 can potentially result in the inhibition of cell proliferation, migration, and invasion. The results proved that miR-570 could potentially function as a tumor suppressor and a potential prognostic factor in patients with colon cancer.

Engineering microbial cell factories has been widely applied to produce compounds spanning from intricate natural products to bulk commodities. In each case, host robustness is essential to ensure the reliable and sustainable production of targeted metabolites. However, it can be negatively affected by metabolic burden, pathway toxicity, and harsh environment, resulting in a decreased titer and productivity. Enhanced robustness enables host to have better production performance under complicated growth circumstances. Here, we review current strategies for boosting host robustness, including metabolic balancing, genetic and phenotype stability enhancement, and tolerance engineering. In addition, we discuss the challenges and future perspectives on microbial host engineering for increased robustness.

Waterfowl parvoviruses (WPVs) including goose parvovirus (GPV), novel GPV-related virus (NGPV) and Muscovy duck parvovirus (MDPV) cause significant economic losses and epizootic threat to the waterfowl industries, and little is known about the B-cell epitopes of WPVs. In this study, a monoclonal antibody (mAb) 5B5 against the VP3 protein of NGPV was used to identify the possible epitope in the three kinds of WPVs. The mAb 5B5 had neutralizing activities to the three viruses, and reacted with the conserved linear B-cell epitopes of 438LHNPPP443 in VP3 protein of GPV, NGPV and MDPV. To the authors' best knowledge, this is the first report on identification of the common conserved neutralizing linear B-cell epitope on VP3 protein of three different WPVs, which would facilitate the development of a novel immunodiagnostic assay for rapid detection of WPV infection.

Duck hepatitis A virus (DHAV), the major pathogen of duck virus hepatitis (DVH), causes severe diseases that threaten the duck industry worldwide. The VP1 protein, a major structural protein of DHAV, is able to induce neutralizing antibody in ducks. The purpose of this study was to identify the antigenic mimotope of DHAV by phage display technology. A monoclonal antibody (mAb) 4E6 against DHAV-1 and DHAV-3 was prepared, and a phage library prepared with the PhD-12 Phage Display Peptide Library Kit was screened with the mAb. A novel peptide, 1GLTWKLPPSM10 was identified with high affinity to the mAb and could specifically block mAb 4E6 from binding DHAV-1 and DHAV-3. Animal tests confirmed that the immunization of ducklings with the mimotope could inhibit the virus proliferation and protect the ducklings from DVH. In summary, the neutralizing conformational mimotope 1GLTWKLPPSM10 might be a promising vaccine candidate for the prevention of DHAV infection.

Rationale Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. Methods After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. Results The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman and V-type nerve agents) were shown to bind more readily to K414 on the peptide. Conclusions This research revealed a new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from that of other nerve agents and providing an important tool for the identification of sarin or cyclosarin in terrorist attacks.

Photometric cues play an important role in recovering per-pixel 3D information from images. Shape from shading and photometric stereo are popular photometric 3D reconstruction approaches, which rely on inversely analyzing an image formation model of the surface normal, reflectance, and lighting. Similarly, shape from polarization explores radiance variation under different polarizer angles to estimate the surface normal, which does not require an active light source and has less restricted assumptions on reflectance and lighting. This chapter reviews basic principles of shape from polarization and its image formation model for surfaces of different reflection properties. We then survey recent progress in shape from polarization combined with different auxiliary information such as geometric cues, spectral cues, photometric cues, and deep learning, and further introduce how polarization imaging benefits other vision tasks in addition to shape recovery.

Autophagy is a tightly regulated catabolic process and is activated in cells in response to stress signals. Despite extensive study, the interplay between duck hepatitis A virus type 1 (DHAV-1) and the autophagy of host cells is not clear. In this study, we applied proteomics analysis to investigate the interaction mechanism between DHAV-1 and duck embryo fibroblast (DEF) cells. In total, 507 differentially expressed proteins (DEPs) were identified, with 171 upregulated proteins and 336 downregulated proteins. The protein expression level of heat shock proteins (Hsps) and their response to stimulus proteins and zinc finger proteins (ZFPs) were significantly increased while the same aspects of ribosome proteins declined. Bioinformatics analysis indicated that DEPs were mainly involved in the &ldquo, response to stimulus&rdquo, the &ldquo, defense response to virus&rdquo, and the &ldquo, phagosome pathway&rdquo, Furthermore, Western blot results showed that the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to the lipidation form of LC3-II increased, and the conversion rate decreased when DEF cells were processed with 4-phenylbutyrate (4-PBA). These findings indicated that DHAV-1 infection could cause endoplasmic reticulum (ER) stress-induced autophagy in DEF cells, and that ER stress was an important regulatory factor in the activation of autophagy. Our data provide a new clue regarding the host cell response to DHAV-1 and identify proteins involved in the DHAV-1 infection process or the ER stress-induced autophagy process.

Simple Summary Duck astrovirus type 1 (DAstV-1) infection constitutes a cause of viral hepatitis in ducklings and little is known about the B-cell epitope of DAstV-1. In this study, using a monoclonal antibody (mAb) 3D2 against ORF2 protein of DAstV-1, a highly conserved linear B-cell epitope of 454 STTESA459 in DAstV-1 ORF2 was identified. The mAb 3D2 showed no neutralizing activity to DAstV-1 and had no cross-reactivity with other DAstV serotypes. Abstract Duck astrovirus type 1 (DAstV-1) infection constitutes a cause of viral hepatitis in ducklings and little is known about the B-cell epitope of DAstV-1. In this study, a monoclonal antibody (mAb) 3D2 against open reading frame 2 (ORF2) protein of DAstV-1 was used to identify the possible epitope in the four serotypes of DAstV. The mAb 3D2 showed no neutralization activity to DAstV-1, and reacted with the conserved linear B-cell epitopes of 454STTESA459 in DAstV-1 ORF2 protein. Sequence analysis, dot blot assay, and cross-reactivity test indicated that the epitope peptide was highly conserved in DAstV-1 sequence and mAb 3D2 had no cross-reactivity with other DAstV serotypes. To the best of our knowledge, this is the first report about identification of the specific conserved linear B-cell epitope of DAstV-1, which will facilitate the serologic diagnosis of DAstV-1 infection.

Writing artificial logic and dynamic function into complex cellular background to achieve desired phenotypes or improved outputs calls for the development of new genetic tools as well as their innovative use. In this study, we present a sensor-regulator and RNAi-based bifunctional dynamic control network that can provide simultaneous upregulation and downregulation of cellular metabolism for engineered biosynthesis. The promoter-regulator-mediated upregulation function and its transduced downregulation function through RNAi are systematically verified and characterized. We apply this dynamic control network to regulate the phosphoenolpyruvate metabolic node in Escherichia coli and achieve autonomous distribution of carbon flux between its native metabolism and the engineered muconic acid biosynthetic pathway. This allows muconic acid biosynthesis to reach 1.8 g L−1. This study also suggests the circumstances where dynamic control approaches are likely to take effects., Engineering dynamic control can improve microbial production of target chemicals. Here, the authors design a sensor-regulator and RNAi based bifunctional dynamic control network that can simultaneously and independently turn up and down cellular metabolism for engineered muconic acid production in E. coli.

The harsh launch environment will cause stress and fracture of propellant charge in the projectile base. If the fracture is serious, it may lead to unsafe launch of the gun. It is one of the important keys and the most difficulties to accurately simulate the gas generation law of fracture propellant charge in the launch safety. In this paper, a dynamic stress and fracture simulation software of propellant charge is established based on the discrete element method, with which the dynamics process of stress and fracture of propellant charge is numerically performed. The corresponding experiments are carried out. According to the computed results of stress and fracture, the new combustion functions are created, and the numerical simulation of the fracture propellant charge combustion in closed bomb is implemented. The numerical simulation results are promising and in good agreement with the closed bomb tests, which indicates that the new combustion functions are effective against simulating the chang...

Sox7, Sox17 and Sox18 are the members of the Sry-related high-mobility group box family (SoxF) of transcription factors. SoxF factors regulate endothelial cell fate as well as development and differentiation of blood cells and lymphatic vessels. There is very less information about the functions of these genes in fish. We obtained the full-length cDNA sequence of SoxF genes including Sox7, Sox17 and Sox18 in Cyprinus carpio, where Sox7 and Sox18 had two copies. The construction of a phylogenetic tree showed that these genes were homologous to the genes in other species. Chromosome synteny analysis indicated that the gene order of Sox7 and Sox18 was highly conserved in fish. However, immense change in genomic sequences around Sox17 had taken place. Numerous putative transcription factor binding sites were identified in the 5_ flanking regions of SoxF genes which may be involved in the regulation of the nervous system, vascular epidermal differentiation and embryonic development. The expression levels of SoxF genes were highest in gastrula, and was abundantly expressed in the adult brain.We investigated the expression levels of SoxF genes in five specific parts of the brain. The expression levels of Sox7 and Sox18 were highest in the mesencephalon, while the expression level of Sox17 was highest in the epencephalon. In carp, the expression patterns of SoxF genes indicated a potential function of these genes in neurogenesis and in vascular development. These results provide new information for further studies on the potential functions of SoxF genes in carp.

As a newly emerged infectious disease, duck "beak atrophy and dwarfism syndrome (BADS)" disease has caused huge economic losses to waterfowl industry in China since 2015. Novel goose parvovirus-related virus (NGPV) is believed the main pathogen of BADS disease; however, BADS is rarely reproduced by infecting ducks with NGPV alone. As avian circovirus infection causes clinical symptoms similar to BADS, duck circovirus (DuCV) is suspected the minor pathogen of BADS disease. In this study, an investigation was carried out to determine the coinfection of NGPV and DuCV in duck embryos and in ducks with BADS disease. According to our study, the coinfection of emerging NGPV and DuCV was prevalent in East China (Shandong, Jiangsu and Anhui province) and could be vertical transmitted, indicating their cooperative roles in duck BADS disease.

2-Methylsuccinic acid (2-MSA) is a C5 branched-chain dicarboxylate that serves as an attractive synthon for the synthesis of polymers with extensive applications in coatings, cosmetic solvents and bioplastics. However, the lack of natural pathways for 2-MSA biosynthesis has limited its application as a promising bio-replacement. Herein, we conceived a non-natural three-step biosynthetic route for 2-MSA, via employing the citramalate pathway in combination with enoate reductase-mediated bioreduction of the pathway intermediate citraconate. First, over-expression of codon-optimized citramalate synthase variant CimA* from Methanococcus jannaschii, endogenous isopropylmalate isomerase EcLeuCD and enoate reductase YqjM from Bacillus subtilis allowed the production of 2-MSA in Escherichia coli for the first time, with a titer of 0.35g/L in shake flask experiments. Subsequent screening of YqjM-like enoate reductases of different bacterial origins enabled identification and characterization of a new NAD(P)H-dependent enoate reductase KpnER from Klebsiella pneumoniae, which exhibited higher activity towards citraconate than YqjM. Incorporation of KpnER into the 2-MSA biosynthetic pathway led to 2-MSA production improvement to a titer of 0.96g/L in aerobic condition. Subsequent optimizations including cofactor regeneration, microaerobic cultivation and host strain engineering, boosted 2-MSA titer to 3.61g/L with a molar yield of 0.36 in shake flask experiments. This work established a promising platform for 2-MSA bioproduction, which enabled the highest titer of 2-MSA production in microbial hosts so far.

A femtosecond pulsed laser was used to perform a processing study on carbon-fiber-reinforced silicon carbide (C/SiC) composites. The effect of femtosecond laser diffraction on the processed morphology was studied by simulation and experiments. Using the diffraction of femtosecond laser, a regular multileveled concentric ring structure was fabricated on the surface of C/SiC composites, and controllable morphology and size could be achieved by changing the processing parameters such as amount of defocus, power, and number of pulses. The results indicate that the spot energy distribution generated by the femtosecond laser diffraction is more uniform than Gaussian beam; therefore, femtosecond laser diffraction can be applied to surface polishing of C/SiC composites.

The suh gene is crucial in Notch pathway and regulates mammalian gonad development. In this study, the sequences of suh1 and suh2 genes in Yellow River carp (Cyprinus carpio) were verified. The partial 5'-flanking regions of suh1 and suh2 were analyzed and several potential transcription factor-binding sites were identified. Phylogenetic, gene structure, and chromosome synteny analyses revealed that carp suh1 and suh2 were orthologs and homologous to vertebrate suh. Investigation of the expression profiles of suh1 and suh2 with qPCR showed that these genes were abundant in the brain and gonad of carp, with suh1 exhibiting sexual dimorphism expression pattern in gonad. To study the relationship between gonad differentiation and Notch signaling, primordial gonads were exposed to DAPT, an inhibitor of Notch signaling, in vitro and in vivo. The results revealed a significant downregulation of suh1 and other Notch genes in vitro. In addition, expression of male-biased genes, such as amh, dmrt1, etc., was downregulated, whereas that of female-biased genes, such as foxl2, gdf9, etc., was upregulated. When the primordial gonads were subjected to long-term DAPT exposure, an increased proportion of ovary and delay in testis development were observed. These results suggest that suh gene may have a conservative function between teleosts and mammals. Furthermore, Notch signaling was found to be involved in gonad differentiation in Yellow River carp, and DAPT was noted to inhibit and enhance the expression of male- and female-biased genes, respectively, and induce the increase in number of females.

Short beak and dwarfism syndrome (SBDS) has been constantly breaking out in China since 2015. It is caused by a novel goose parvovirus-related virus (NGPV) and can severely restrict the growth of ducks. In this study, seven NGPV stains were isolated from different regions in China between 2015 and 2016. To better understand the correlation between NGPV and goose parvovirus (GPV), we conducted complete genome sequencing and a comprehensive analysis of the NGPV genome. The phylogenetic and alignment analysis showed that NGPV is a branch of GPV, sharing 92.2%-97.1% nucleotide identity with GPV. Compared with classical GPV, five consensus nucleotide mutations in all the seven NGPV isolates and two 14-nucleotide-pair deletions in six NGPV isolates were found in the inverted terminal repeats, twelve and eight synchronous amino acid changes were found in the replication protein and capsid protein of NGPV, respectively, which might be important for viral gene regulation, humoral immune responses, and host transfer. Notably, SDLY1602 was demonstrated a recombinant strain, with the potential major parent GPV vaccine strain 82-0321v and the minor parent GPV wild strain GDaGPV. This is the first report showing that the recombination between two classical GPV strains generated a NGPV strain circulating in nature. This study will advance our understanding of NGPV molecular biology and facilitate to elucidate the evolutionary characteristics of GPV.

Duck short beak and dwarfism syndrome (SBDS) is an emerging infectious disease caused by a novel goose parvovirus-related virus (NGPV) in China. Until now, it remains uncertain whether the Cherry Valley ducks and mule ducks with SBDS are co-infected with classical goose parvovirus (GPV) and NGPV. In this study, a duplex semi-nested PCR assay with high specificity and sensitivity was developed for detection of the two viruses. Using the duplex PCR assay, NGPV was tested positive in all the 15 duck flocks with SBDS, whereas classical GPV was not detected in all the 133 sick and dead ducks collected from East China. A total of 87 (91.58%) Cherry Valley ducks aged from 5 to 18 days and 35 (92.11%) mule ducks aged from 17 to 25 days were detected positive for NGPV. In the NGPV-positive ducks, the virus detection rates were 81.97% to 8.20% in heart, liver, spleen, lung, kidney, pancreas, bile, thymus, bursa of Fabricius, and brain. The results indicated that NGPV was prevalent in the duck flocks of East China, whereas classical GPV was not detected in Cherry Valley ducks and mule ducks with SBDS. NGPV has extensive tissue tropism in Cherry Valley duck and mule duck, which could invade both the central and peripheral immune organs and break through the blood-brain barrier of ducks.

Vanillyl alcohol is a phenolic alcohol and is used as a flavoring agent in foods and beverages. In this paper, we propose a novel artificial pathway for microbial production of vanillyl alcohol from simple carbon sources. The pathway extends from 4-hydroxybenzoic acid (4-HBA), and needs only three heterologous enzymes, p-hydroxybenzoate hydroxylase (PobA), carboxylic acid reductase (CAR) and caffeate O-methyltransferase (COMT). First, we examined the promiscuous activity of COMT toward 3,4-dihydroxybenzyl alcohol and found a kcat value of 0.097 s–1. Meanwhile, 499.36 mg/L vanillyl alcohol was produced by COMT in vivo catalysis when fed with 1000 mg/L 3,4-dihydroxybenzyl alcohol. In the following experiment, de novo biosynthesis of vanillyl alcohol was carried out and 240.69 mg/L vanillyl alcohol was produced via modular optimization of pathway genes. This work was to date the first achievement for microbial production of vanillyl alcohol. Additionally, the present study demonstrates the application of enz...

CBLB502 derived from Salmonella flagellin is a novel agonist of Toll-like receptor 5 (TLR5). It has been shown that CBLB502 can exert high radioprotective efficacy on mice and primates from both GI and hematopoietic syndromes during whole-body irradiation with low toxicity and immunogenicity. However, no effective system has been used to investigate the protective effect of CBLB502 against irradiation and the related mechanism in vitro. In this study, we investigated the radioprotective properties of CBLB502 in HEK293-N-T cells constitutively expressing human TLR5 and NF-κB-dependent luciferase. HEK293-N-T cells were treated with different doses of CBLB502 prior to 60Co-γ ray irradiation. After irradiation, cell viability was real-time measured for 4 days by using the real-time cell analysis system. We found that CBLB502 was capable of efficiently maintaining the survival rate of irradiated HEK293-N-T cells. Then apoptotic cell death and cell cycle were detected by flow cytometry. The results showed that CBLB502 pre-treatment could reduce the apoptosis and promote the recovery of irradiated HEK293-N-T cells from G2-phase arrest in a dose-dependent manner. Our data indicated that CBLB502 has a direct radioprotective effect in vitro via anti-apoptosis and promotes cell cycle recovery. The method developed here could be an effective in vitro system to screen other TLR5-target radioprotectants like CBLB502.

Aiming at the difficulty that the actual burning law of propellant in the gun bore couldn't be described exactly by static burning rate equation in the closed-bomb, propellant dynamic burning rate equation and its acquisition method were established in the paper, which are based on static burning rate equation and considering burning gas flow and loading density influence factors in bore. A numerical code for interior ballistic two-phase flow was successfully developed. And corresponding firing tests were also carried out. The comparison of simulations with interior ballistic code and firing test results show that the propellant dynamic burning rate equation makes the maximum errors of muzzle velocity and pressure in breech decreased from 2.97 % to 0.75 % and from 6.68 % to 0.38 %, respectively. This method not only improves simulation precision of gun muzzle velocity and pressure significantly, but also provides a means to improve the design accuracy for interior ballistic performance.

T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naive CD4+ T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.

Background The tools of synthetic biology have enabled researchers to explore multiple scientific phenomena by directly engineering signaling pathways within living cells and artificial protocells. Here, we explored the potential for engineered living cells themselves to assemble signaling pathways for non-living protocells. This analysis serves as a preliminary investigation into a potential origin of processes that may be utilized by complex living systems. Specifically, we suggest that if living cells can be engineered to direct the assembly of genetic signaling pathways from genetic biomaterials in their environment, then insight can be gained into how naturally occurring living systems might behave similarly.

Twenty ISSR markers were used to amplify the genome of Brassica campestris L. ssp. chinensis Makino (Pak-choi). A total of 173 scorable alleles have been detected among 68 B. campestris genotypes, and the polymorphic alleles was 84.21%. Average diversity index (I) was 0.4284, and the mean number of the per locus of effective alleles was 1.4796. Moreover, the mean value of the Nei’s gene diversity (He) was 0.2883. The results revealed a higher genetic diversity in B. campestris from China than that from Japan and Thailand. The dendrogram divided the 68 B. campestris accessions into four groups. The dendrogram clustered the accessions of similar morphology together, and it indicated that the samples from the same geographical region were much closer than those from different regions. Meanwhile, the dendrogram also revealed that male sterile lines and their maintainer lines clustered together.