Composite patch with negative Poisson's ratio mimicking cardiac mechanical properties: Design, experiment and simulation.

Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.

Hydrogels composite optimized for low resistance and loading-unloading hysteresis for flexible biosensors.

With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities. At 95 % strain, the compressive modulus of PAA/NB/IL 100 reach up to 3.66 MPa, with the loading-unloading process showing no significant hysteresis loop, indicating strong mechanical stability and elasticity. An increase in the IL content was observed to enlarge the porosity of the hydrogels, thereby influencing their swelling behavior and sensing functionality. Biocompatibility assessments revealed that the hemolysis rate was below 5 %, ensuring their suitability for biomedical applications. Upon implantation in rats, a minimal acute inflammatory response was observed, comparable to that of the biocompatibility control poly(ethylene glycol) diacrylate (PEGDA). These results suggest that PAA/NB/IL hydrogels hold promise as biomaterials for biosensors, offering a balance of mechanical integrity, physiological compatibility, and sensing sensitivity, thereby facilitating advanced healthcare monitoring solutions.

Light-Responsive Soft Robot Integrating Actuation and Function Based on Laser Cutting.

Soft robots with good deformability and adaptability have important prospects in the bionics and intelligence field. However, current research into soft robots is primarily limited to the study of actuators and ignores the integrated use of functional devices and actuators. To enrich the functions of soft robots and expand their application fields, it is necessary to integrate various functional electronic devices into soft robots to perform diverse functions during dynamic deformation. Therefore, this paper discusses methods and strategies to manufacture optical stimuli-responsive soft actuators and integrate them into functional devices for soft robots. Specifically, laser cutting allows us to fabricate an optically responsive actuator structure, e.g., the curling direction can be controlled by adjusting the direction of the cutting line. Actuators with different bending curvatures, including nonbending, can be obtained by adjusting the cutting depth, cutting width, and the spacing of the cutting line, which makes it easy to obtain a folded structure. Thus, various actuators with complex shape patterns can be obtained. In addition, we demonstrate a fabrication scheme for a worm-like soft robot integrated with functional devices (LEDs are used in this paper). The local nonbending design provides an asymmetric structure that provides driving power and avoids damage to the functional circuit caused by the large deformation during movement. The integration of drive and function provides a new path for the application of soft robots in the intelligence and bionics field.

Degradable biomedical elastomers: paving the future of tissue repair and regenerative medicine.

Degradable biomedical elastomers (DBE), characterized by controlled biodegradability, excellent biocompatibility, tailored elasticity, and favorable network design and processability, have become indispensable in tissue repair. This review critically examines the recent advances of biodegradable elastomers for tissue repair, focusing mainly on degradation mechanisms and evaluation, synthesis and crosslinking methods, microstructure design, processing techniques, and tissue repair applications. The review explores the material composition and cross-linking methods of elastomers used in tissue repair, addressing chemistry-related challenges and structural design considerations. In addition, this review focuses on the processing methods of two- and three-dimensional structures of elastomers, and systematically discusses the contribution of processing methods such as solvent casting, electrostatic spinning, and three-/four-dimensional printing of DBE. Furthermore, we describe recent advances in tissue repair using DBE, and include advances achieved in regenerating different tissues, including nerves, tendons, muscle, cardiac, and bone, highlighting their efficacy and versatility. The review concludes by discussing the current challenges in material selection, biodegradation, bioactivation, and manufacturing in tissue repair, and suggests future research directions. This concise yet comprehensive analysis aims to provide valuable insights and technical guidance for advances in DBE for tissue engineering.

Water-Responsive 3D Electronics for Smart Biological Interfaces.

Three-dimensional (3D) electronic systems with their potential for enhanced functionalities often require complex fabrication processes. This paper presents a water-based, stimuli-responsive approach for creating self-assembled 3D electronic systems, particularly suited for biorelated applications. We utilize laser scribing to programmatically shape a water-responsive bilayer, resulting in smart 3D electronic substrates. Control over the deformation direction, actuation time, and surface curvature of rolling structures is achieved by adjusting laser-scribing parameters, as validated through experiments and numerical simulations. Additionally, self-locking structures maintain the integrity of the 3D systems. This methodology enables the implementation of spiral twining electrodes for electrophysiological signal monitoring in plants. Furthermore, the integration of self-rolling electrodes onto peripheral nerves in a rodent model allows for stimulation and recording of in vivo neural activities with excellent biocompatibility. These innovations provide viable paths to next-generation 3D biointegrated electronic systems for life science studies and medical applications.

Removal of nitrate by FeSiBC metallic glasses: high efficiency and superior reusability.

The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.

DBLiPro: A Database for Lipids and Proteins in Human Lipid Metabolism.

To help researchers in the field of biology, medicine, chemistry, and materials science to use lipidomic data conveniently, there is an urgent need to develop a platform that provides a systematic knowledgebase of human lipid metabolism and lipidome-centric omics analysis tools. DBLiPro is a user-friendly webserver allowing for access to human metabolism-related lipids and proteins knowledge database and an interactive bioinformatics integrative analysis workflow for lipidomics, transcriptomics, and proteomics data. In DBLiPro, there are 3109 lipid-associated proteins (LAPs) and 2098 lipid metabolites in the knowledge base section, which were obtained from Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and were further annotated by information from other public resources in the knowledge base section, such as RaftProt and PubChem. DBLiPro offers a step-by-step interactive analysis workflow for lipidomics, transcriptomics, proteomics, and their integrating multi-omics analysis focusing on the human lipid metabolism. In summary, DBLiPro is capable of helping users discover key molecules (lipids and proteins) in human lipid metabolism and investigate lipid-protein functions underlying mechanisms based on their own omics data. The DBLiPro is freely available at http://lipid.cloudna.cn/home.

Zn2+-interference and H2S-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer.

Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.

Recent progress of antibacterial hydrogels in wound dressings.

Hydrogels are essential biomaterials due to their favorable biocompatibility, mechanical properties similar to human soft tissue extracellular matrix, and tissue repair properties. In skin wound repair, hydrogels with antibacterial functions are especially suitable for dressing applications, so novel antibacterial hydrogel wound dressings have attracted widespread attention, including the design of components, optimization of preparation methods, strategies to reduce bacterial resistance, etc. In this review, we discuss the fabrication of antibacterial hydrogel wound dressings and the challenges associated with the crosslinking methods and chemistry of the materials. We have investigated the advantages and limitations (antibacterial effects and antibacterial mechanisms) of different antibacterial components in the hydrogels to achieve good antibacterial properties, and the response of hydrogels to stimuli such as light, sound, and electricity to reduce bacterial resistance. Conclusively, we provide a systematic summary of antibacterial hydrogel wound dressings findings (crosslinking methods, antibacterial components, antibacterial methods) and an outlook on long-lasting antibacterial effects, a broader antibacterial spectrum, diversified hydrogel forms, and the future development prospects of the field.

Correlation analysis of carotid artery intima-media thickness, serum 25(OH)D and men with erectile dysfunction.

Our goal is to investigate the connection between serum 25(OH)D and carotid artery intima-media thickness (CIMT) in men with erectile dysfunction (ED).Serum 25(OH)D and CIMT were measured in 124 participants with erectile dysfunction and 39 healthy controls. The relationship between them and different patient-related parameters and disease-related parameters was studied. Compared with the control group and mild ED group, the level of serum 25(OH)D in moderate ED group and severe ED group decreased significantly(P<0.05). The CIMT values of moderate ED group and severe ED group were higher than those of the control group(P<0.05). The CIMT value of severe ED group was significantly higher than that of mild ED group(P<0.05). IIEF-5 score was positively correlated with serum 25(OH)D level, but negatively correlated with CIMT value(P<0.05). After adjusting for the influence of confounding factors, The CIMT values, 25(OH)D and IIEF-5 score were substantially associated(P<0.05). The serum level of 25(OH)D and IIEF-5 score were positively correlated, while the CIMT values and IIEF-5 score were negatively correlated. The level of serum 25(OH)D should be analyzed in men with ED, especially in patients with vasculogenic ED, and supplementation is recommended for those who were with vitamin D deficiency.

[Ten-year Trend Analysis of Eutrophication Status and the Related Causes in Lake Hongze].

In order to propose pertinent suggestions regarding eutrophication control for Lake Hongze, we used monthly monitoring data from 2011 to 2020 to elucidate the spatiotemporal changing characteristics of eutrophic status and the relevant driving factors. As the main river entering Lake Hongze, River Huaihe experienced an increase in permanganate index and a decrease in TN in the last 10 years. Meanwhile, Secchi depth, TP, and permanganate index increased, whereas TN and Chl-a concentration decreased significantly in Lake Hongze. As a result, the eutrophic status TLI index of Lake Hongze declined over the past 10 years. The change trend of TLI in Lake Hongze differed spatially. As the main water passage of River Huaihe, the algal biomass was lower in the eastern region than that in the other two lake regions, regardless of the relatively high nutrient concentration, due to the short water retention time. Furthermore, the water quality of River Huaihe improved; thus, the TLI index decreased significantly in the eastern lake region. The northern region had a high coverage of aquatic vegetation, which not only reduced the concentration of water nutrients but also provided a habitat for zooplankton and fish, effectively inhibiting algal growth. Thus, the TLI index was lowest among the three lake areas and showed a downward trend over the last 10 years. In the western region, the algal biomass was the highest due to the intensification of phosphorus release from sediment in summer. Thus, the TLI index was the highest and had not improved in the past 10 years. There were also significant seasonal differences in the TLI of Lake Hongze, which was highest in summer, due to the relatively high algal biomass. Moreover, the algal biomass in summer was mainly affected by the concentration of nitrate. According to the spatiotemporal distribution characteristics of eutrophic status and the impacting factors in Lake Hongze, corresponding measures for eutrophication control should be taken for different seasons and lake areas.

SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

Effect of pH on the Conformational Transition of Silk Fibroin in Aqueous Solution Monitored by Thioflavin-T Fluorescence.

In this work, the potential application of the fluorescence dye Thioflavin-T (ThT), which can specifically bind to amyloid, as a powerful tool for monitoring secondary structural transitions of silk fibroin (SF) induced by pH in low solution concentrations was examined. Results showed that ThT emission intensities substantially increased when pH decreased from 6.8 to 4.8. This increase may be ascribed to conformational transitions from random coil to ß-sheet. The morphology and secondary structure of SF were also investigated via TEM, AFM and circular dichroism spectroscopy. The information obtained herein can be utilized not only for the development of convenient and efficient noninvasive method for monitoring the assembly behavior of SF in aqueous solution but also for in vitro fluorescence imaging.

Metabolism analysis of 17α-ethynylestradiol by Pseudomonas citronellolis SJTE-3 and identification of the functional genes.

Synthetic estrogens are the most hazardous and persistent environmental estrogenic contaminants, with few reports on their biodegradation. Pseudomonas citronellolis SJTE-3 degraded natural steroids efficiently and metabolized 17α-ethynylestradiol (EE2) with the addition of different easily used energy sources (glucose, peptone, ethanol, yeast extract, fulvic acid and ammonia). Over 92% of EE2 (1 mg/L) and 55% of EE2 (10 mg/L) in culture were removed in seven days with the addition of 0.1% ethanol, and the EE2-biotransforming efficiency increased with the increasing ethanol concentrations. Two novel intermediate metabolites of EE2 (C22H22O and C18H34O2) were identified with high-performance liquid chromatography (HPLC) and GC-Orbitrap/MS. Comparative analysis and genome mining revealed strain SJTE-3 contained a unique genetic basis for EE2 metabolism, and the putative EE2-degrading genes exhibited dispersed distribution. The EE2 metabolism of strain SJTE-3 was inducible and the transcription of eight genes were significantly induced by EE2. Three genes (sdr3, yjcH and cyp2) encoding a short-chain dehydrogenase, a membrane transporter and a cytochrome P450 hydroxylase, respectively, were vital for EE2 metabolism in strain SJTE-3; their over-expression accelerated EE2 metabolic processes and advanced the generation of intermediate metabolites. This work could promote the study of bacterial EE2 metabolism mechanisms and facilitate efficient bioremediation for EE2 pollution.

Predictive Model and Precaution for Oral Mucositis During Chemo-Radiotherapy in Nasopharyngeal Carcinoma Patients.

PURPOSE: To explore risk factors for severe acute oral mucositis of nasopharyngeal carcinoma (NPC) patients receiving chemo-radiotherapy, build predictive models and determine preventive measures. METHODS AND MATERIALS: Two hundred and seventy NPC patients receiving radical chemo-radiotherapy were included. Oral mucosa structure was contoured by oral cavity contour (OCC) and mucosa surface contour (MSC) methods. Oral mucositis during treatment was prospectively evaluated and divided into severe mucositis group (grade ≥ 3) and non-severe mucositis group (grade < 3) according to RTOG Acute Reaction Scoring System. Nineteen clinical features and nineteen dosimetric parameters were included in analysis, least absolute shrinkage and selection operator (LASSO) logistic regression model was used to construct a risk score (RS) system. RESULTS: Two predictive models were built based on the two delineation methods. MSC based model is more simplified one, it includes body mass index (BMI) classification before radiation, retropharyngeal lymph node (RLN) area irradiation status and MSC V55%, RS = -1.480 + (0.021 × BMI classification before RT) + (0.126 × RLN irradiation) + (0.052 × MSC V55%). The cut-off of MSC based RS is -1.011, with an area under curve (AUC) of 0.737 (95%CI: 0.672-0.801), a specificity of 0.595 and a sensitivity of 0.786. OCC based model involved more variables, RS= -4.805+ (0.152 × BMI classification before RT) + (0.080 × RT Technique) + (0.097 × Concurrent Nimotuzumab) + (0.163 × RLN irradiation) + (0.028 × OCC V15%) + (0.120 × OCC V60%). The cut-off of OCC based RS is -0.950, with an AUC of 0.767 (95%CI: 0.702-0.831), a specificity of 0.602 and a sensitivity of 0.819. Analysis in testing set shown higher AUC of MSC based model than that of OCC based model (AUC: 0.782 vs 0.553). Analysis in entire set shown AUC in these two method-based models were close (AUC: 0.744 vs 0.717). CONCLUSION: We constructed two risk score predictive models for severe oral mucositis based on clinical features and dosimetric parameters of nasopharyngeal carcinoma patients receiving chemo-radiotherapy. These models might help to discriminate high risk population in clinical practice that susceptible to severe oral mucositis and individualize treatment plan to prevent it.

Discovery and characterization of the evolution, variation and functions of diversity-generating retroelements using thousands of genomes and metagenomes.

BACKGROUND: Diversity-generating retroelements (DGRs) are a unique family of retroelements that generate sequence diversity of DNA to benefit their hosts by introducing variations and accelerating the evolution of target proteins. They exist widely in bacteria, archaea, phage and plasmid. However, our understanding about DGRs in natural environments was still very limited. RESULTS: We developed an efficient computational algorithm to identify DGRs, and applied it to characterize DGRs in more than 80,000 sequenced bacterial genomes as well as more than 4,000 human metagenome datasets. In total, we identified 948 non-redundant DGRs, which expanded the number of known DGRs in bacterial genomes and human microbiomes by about 55%, and provided a much more comprehensive reference for the study of DGRs. Phylogenetic analysis was done for identified DGRs. The putative target genes of DGRs were searched, and the functions of these target genes were investigated with a comprehensive alignment against the nr database. CONCLUSIONS: DGR system is a powerful and universal mechanism to generate diversity. DGR evolution is closely associated with the living environment and their cassette structures. Furthermore, it may impact a wide range of functional processes in addition to receptor-binding. These results significantly improved our understanding about DGRs.

PaSS: a sequencing simulator for PacBio sequencing.

BACKGROUND: Third-generation sequencing platforms, such as PacBio sequencing, have been developed rapidly in recent years. PacBio sequencing generates much longer reads than the second-generation sequencing (or the next generation sequencing, NGS) technologies and it has unique sequencing error patterns. An effective read simulator is essential to evaluate and promote the development of new bioinformatics tools for PacBio sequencing data analysis. RESULTS: We developed a new PacBio Sequencing Simulator (PaSS). It can learn sequence patterns from PacBio sequencing data currently available. In addition to the distribution of read lengths and error rates, we included a context-specific sequencing error model. Compared to existing PacBio sequencing simulators such as PBSIM, LongISLND and NPBSS, PaSS performed better in many aspects. Assembly tests also suggest that reads simulated by PaSS are the most similar to experimental sequencing data. CONCLUSION: PaSS is an effective sequence simulator for PacBio sequencing. It will facilitate the evaluation and development of new analysis tools for the third-generation sequencing data.

Silencing of SAA1 inhibits palmitate- or high-fat diet induced insulin resistance through suppression of the NF-κB pathway.

BACKGROUND: Obesity is one of the leading causes of insulin resistance. Accumulating reports have highlighted that serum amyloid A-1 (SAA1) is a potential candidate that is capable of attenuating insulin resistance. Hence, we conducted the current study with aims of investigating our proposed hypothesis that silencing SAA1 could inhibit the progression of obesity-induced insulin resistance through the NF-κB pathway. METHODS: Gene expression microarray analysis was initially performed to screen differentially expressed genes (DEGs) associated with obesity. Palmitate (PA)-induced insulin resistance Huh7 cell models and high-fat diet (HFD)-induced mouse models were established to elucidate the effect of SAA1/Saa1 on insulin resistance. The NF-κB pathway-related expression was subsequently determined through the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. RESULTS: Saa1 was identified as an obesity-related gene based on the microarray data of GSE39549. Saa1 was determined to be highly expressed in HFD-induced insulin resistance mouse models. PA-induced Huh7 cells, treated with silenced SAA1 or NF-κB pathway inhibition using BAY 11-7082, displayed a marked decrease in both Saa1 and SOCS3 as well as an elevation in 2DG, IRS1 and the extent of IRS1 phosphorylation. HFD mice treated with silenced Saa1 or inhibited NF-κB pathway exhibited improved fasting blood glucose (FBG) levels as well as fasting plasma insulin (FPI) levels, glucose tolerance and systemic insulin sensitivity. Saa1/SAA1 was determined to show a stimulatory effect on the transport of the NF-κBp65 protein from the cytoplasm to the nucleus both in vivo and in vitro, suggesting that Saa1/SAA1 could activate the NF-κB pathway. CONCLUSION: Taken together, our key findings highlight a novel mechanism by which silencing of SAA1 hinders PA or HFD-induced insulin resistance through inhibition of the NF-κB pathway.

Transcriptional Sequencing Uncovers Survival Mechanisms of Salmonella enterica Serovar Enteritidis in Antibacterial Egg White.

The survival mechanism of Salmonella enterica serovar Enteritidis in antibacterial egg white is not fully understood. In our lab, an egg white-resistant strain, S. Enteritidis SJTUF 10978, was identified. Cell envelope damage and osmotic stress response (separation of cell wall and inner membrane as well as cytoplasmic shrinkage) of this strain surviving in egg white were identified through microscopic observation. RNA-Seq analysis of the transcriptome of Salmonella survival in egg white showed that a considerable number of genes involved in DNA damage repair, alkaline pH adaptation, osmotic stress adaptation, envelope damage repair, Salmonella pathogenicity island 2 (SPI-2), iron absorption, and biotin synthesis were significantly upregulated (fold change ≥ 2) in egg white, indicating that these pathways or genes might be critical for bacterial survival. RNA-Seq results were confirmed by qRT-PCR, and the survival analysis of six gene deletion mutants confirmed their importance in the survival of bacteria in egg white. The importance of alkaline pH adaptation and envelope damage repair for Salmonella to survive in egg white were further confirmed by analysis of nhaA, cpxR, waaH, and eco deletion mutants. According to the RNA-Seq results, we propose that alkaline pH adaptation might be the cause of bacterial osmotic stress phenotype and that the synergistic effect between alkaline pH and other inhibitory factors can enhance the bacteriostatic effect of egg white. Moreover, cpxR and sigE were recognized as the central regulators that coordinate bacterial metabolism to adapt to envelope damage and alkaline pH.IMPORTANCESalmonella enterica serovar Enteritidis is a major foodborne pathogen that causes salmonellosis mainly through contaminated chicken eggs or egg products and has been a worldwide public health threat since 1980. Frequent outbreaks of this serotype through eggs correlate significantly with its exceptional survival ability in the antibacterial egg white. Research on the survival mechanism of S. Enteritidis in egg white will help to further understand the complex and highly effective antibacterial mechanisms of egg white and lay the foundation for the development of safe and effective vaccines to prevent egg contamination by this Salmonella serotype. Key pathways and genes that were previously overlooked under bactericidal conditions were characterized as being induced in egg white, and synergistic effects between different antimicrobial factors appear to exist according to the gene expression changes. Our work provides new insights into the survival mechanism of S. Enteritidis in egg white.

GLAPD: Whole Genome Based LAMP Primer Design for a Set of Target Genomes.

Loop-mediated isothermal amplification (LAMP) technology has been applied in a wide range of fields such as detection of foodborne bacteria and clinical pathogens due to its simplicity and efficiency. However, existing LAMP primer designing systems require a conserved gene or a short genome region as input, and they can't design group-specific primers. With the growing number of whole genomes available, it is possible to design better primers to target a set of genomes with high specificity based on whole genomes. We present here a whole Genome based LAMP primer designer (GLAPD), a new system to design LAMP primer for a set of target genomes using whole genomes. Candidate single primer regions are identified genome wide and then combined into LAMP primer sets. For a given set of target genomes, only primer sets amplifying them and only these genomes will be output. In order to accelerate the primer designing, a GPU version is provided as well. The effectiveness of primers designed by GLAPD has been assessed for a wide range of foodborne bacteria. GLAPD can be accessed at http://cgm.sjtu.edu.cn/GLAPD/ or https://github.com/jiqingxiaoxi/GLAPD.git. A simple online version is also supplied to help users to learn and test GLAPD: http://cgm.sjtu.edu.cn/GLAPD/online/.