Animal-SNPAtlas: a comprehensive SNP database for multiple animals.

Single-nucleotide polymorphisms (SNPs) as the most important type of genetic variation are widely used in describing population characteristics and play vital roles in animal genetics and breeding. Large amounts of population genetic variation resources and tools have been developed in human, which provided solid support for human genetic studies. However, compared with human, the development of animal genetic variation databases was relatively slow, which limits the genetic researches in these animals. To fill this gap, we systematically identified ∼ 499 million high-quality SNPs from 4784 samples of 20 types of animals. On that basis, we annotated the functions of SNPs, constructed high-density reference panels and calculated genome-wide linkage disequilibrium (LD) matrixes. We further developed Animal-SNPAtlas, a user-friendly database (http://gong_lab.hzau.edu.cn/Animal_SNPAtlas/) which includes high-quality SNP datasets and several support tools for multiple animals. In Animal-SNPAtlas, users can search the functional annotation of SNPs, perform online genotype imputation, explore and visualize LD information, browse variant information using the genome browser and download SNP datasets for each species. With the massive SNP datasets and useful tools, Animal-SNPAtlas will be an important fundamental resource for the animal genomics, genetics and breeding community.

Amorphous Oxyhalide Matters for Achieving Lithium Superionic Conduction.

The recently surged halide-based solid electrolytes (SEs) are great candidates for high-performance all-solid-state batteries (ASSBs), due to their decent ionic conductivity, wide electrochemical stability window, and good compatibility with high-voltage oxide cathodes. In contrast to the crystalline phases in halide SEs, amorphous components are rarely understood but play an important role in Li-ion conduction. Here, we reveal that the presence of amorphous component is common in halide-based SEs that are prepared via mechanochemical method. The fast Li-ion migration is found to be associated with the local chemistry of the amorphous proportion. Taking Zr-based halide SEs as an example, the amorphization process can be regulated by incorporating O, resulting in the formation of corner-sharing Zr-O/Cl polyhedrons. This structural configuration has been confirmed through X-ray absorption spectroscopy, pair distribution function analyses, and Reverse Monte Carlo modeling. The unique structure significantly reduces the energy barriers for Li-ion transport. As a result, an enhanced ionic conductivity of (1.35 ± 0.07) × 10-3 S cm-1 at 25 °C can be achieved for amorphous Li3ZrCl4O1.5. In addition to the improved ionic conductivity, amorphization of Zr-based halide SEs via incorporation of O leads to good mechanical deformability and promising electrochemical performance. These findings provide deep insights into the rational design of desirable halide SEs for high-performance ASSBs.

Lithium Pre-Storage Enables High Initial Coulombic Efficiency and Stable Lithium-Enriched Silicon/Graphite Anode.

Application of silicon-based anodes is significantly challenged by low initial Coulombic efficiency (ICE) and poor cyclability. Traditional pre-lithiation reagents often pose safety concerns due to their unstable chemical nature. Achieving a balance between water-stability and high ICE in prelithiated silicon is a critical issue. Here, we present a lithium-enriched silicon/graphite material with an ultra-high ICE of ≥110 % through a high-stable lithium pre-storage methodology. Lithium pre-storage prepared a nano-drilled graphite material with surficial lithium functional groups, which can form chemical bonds with adjacent silicon during high-temperature sintering. This results in an unexpected O-Li-Si interaction, leading to in situ pre-lithiation of silicon nanoparticles and providing high stability in air and water. Additionally, the lithium-enriched silicon/graphite materials impart a combination of high ICE, high specific capacity (620 mAh g-1), and long cycling stability (>400 cycles). This study opens up a promising avenue for highly air- and water-stable silicon anode prelithiation methods.

A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

Reviving Cost-Effective Organic Cathodes in Halide-Based All-Solid-State Lithium Batteries.

The evolution of inorganic solid electrolytes has revolutionized the field of sustainable organic cathode materials, particularly by addressing the dissolution problems in traditional liquid electrolytes. However, current sulfide-based all-solid-state lithium-organic batteries still face challenges such as high working temperatures, high costs, and low voltages. Here, we design an all-solid-state lithium battery based on a cost-effective organic cathode material phenanthrenequinone (PQ) and a halide solid electrolyte Li2ZrCl6. Thanks to the good compatibility between PQ and Li2ZrCl6, the PQ cathode achieved a high specific capacity of 248 mAh g-1 (96 % of the theoretical capacity), a high average discharge voltage of 2.74 V (vs. Li+/Li), and a good capacity retention of 95 % after 100 cycles at room temperature (25 °C). Furthermore, the interactions between the high-voltage carbonyl PQ cathode and both sulfide and halide solid electrolytes, as well as the redox mechanism of the PQ cathode in all-solid-state batteries, were carefully studied by a variety of advanced characterizations. We believe such a design and the corresponding investigations into the underlying chemistry give insights for the further development of practical all-solid-state lithium-organic batteries.

The status and trends of mitochondrial dynamics research: A global bibliometric and visualized analysis.

BACKGROUND: Mitochondria are remarkably dynamic organelles encapsulated by bilayer membranes. The dynamic properties of mitochondria are critical for energy production. AIMS: The aim of our study is to investigate the global status and trends of mitochondrial dynamics research and predict popular topics and directions in the field. METHODS: Publications related to the studies of mitochondrial dynamics from 2002 to 2021 were retrieved from Web of Science database. A total of 4,576 publications were included. Bibliometric analysis was conducted by visualization of similarities viewer and GraphPadPrism 5 software. RESULTS: There is an increasing trend of mitochondrial dynamics research during the last 20 years. The cumulative number of publications about mitochondrial dynamics research followed the logistic growth model [Formula: see text]. The USA made the highest contributions to the global research. The journal Biochimica et Biophysica Acta (BBA)-Molecular Cell Research had the largest publication numbers. Case Western Reserve University is the most contributive institution. The main research orientation and funding agency were cell biology and HHS. All keywords related studies could be divided into three clusters: "Related disease research", "Mechanism research" and "Cell metabolism research". CONCLUSIONS: Attention should be drawn to the latest popular research and more efforts will be put into mechanistic research, which may inspire new clinical treatments for the associated diseases.

Current oscillations from bipolar nanopores for statistical monitoring of hydrogen evolution on a confined electrochemical catalyst.

Taking advantage of bipolar electrochemistry and a glass nanopipette, continuous single bubbles can be controlled which are generated and detached from a nanometer-sized area of confined electrochemical catalysts. The observed current oscillations offer opportunities to rapidly collect data for the statistical analysis of single-bubble generation on and departure from the catalysts.

Plant-ImputeDB: an integrated multiple plant reference panel database for genotype imputation.

Genotype imputation is a process that estimates missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs), boost the power to identify genetic association and promote the combination of genetic studies. However, there has been a lack of high-quality reference panels for most plants, which greatly hinders the application of genotype imputation. Here, we developed Plant-ImputeDB (http://gong_lab.hzau.edu.cn/Plant_imputeDB/), a comprehensive database with reference panels of 12 plant species for online genotype imputation, SNP and block search and free download. By integrating genotype data and whole-genome resequencing data of plants from various studies and databases, the current Plant-ImputeDB provides high-quality reference panels of 12 plant species, including ∼69.9 million SNPs from 34 244 samples. It also provides an easy-to-use online tool with the option of two popular tools specifically designed for genotype imputation. In addition, Plant-ImputeDB accepts submissions of different types of genomic variations, and provides free and open access to all publicly available data in support of related research worldwide. In general, Plant-ImputeDB may serve as an important resource for plant genotype imputation and greatly facilitate the research on plant genetic research.

LncRNA CRNDE Exacerbates IgA Nephropathy Progression by Promoting NLRP3 Inflammasome Activation in Macrophages.

BACKGROUND: Activation of NLRP3 inflammasome in macrophages contributes greatly to IgA nephropathy (IgAN) progression. This study intended to investigate the underlying mechanism of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in the development of IgAN. METHODS: We examined the expression levels of colorectal neoplasia differentially expressed (CRNDE), NLRP3 inflammasome-related proteins in peripheral blood mononuclear cells (PBMCs) and J774A.1 cells and detected inflammatory cytokine levels in the serum of IgAN patients and cell supernatants of in vitro IgAN model. RNA pull-down and RNA immunoprecipitation (RIP) experiments were conducted to evaluate the interaction between CRNDE and NLRP3. Then, the ubiquitin level of NLRP3 and its binding ability to TRIM family member 31 (TRIM31) were determined. RESULTS: Compared with the control group, the expressions of CRNDE and NLRP3 inflammasome-related proteins in PBMCs and J774A.1 cells and levels of IL-1ß, TNF-α and IL-12 in serum of IgAN patients and cell supernatants of IgA-IC-induced J774A.1 cells were all increased. CRNDE silencing down-regulated NLRP3 inflammasome-related proteins and the levels of IL-1ß, TNF-α and IL-12 in cell supernatants, while NLRP3 overexpression reversed these effects. Additionally, CRNDE could interact with NLRP3 and promote NLRP3 expression. Furthermore, inhibition of CRNDE reduced NLRP3 protein level and promoted TRIM31-mediated NLRP3 ubiquitination and degradation. CONCLUSION: CRNDE exacerbates IgA nephropathy progression through restraining ubiquitination and degradation of NLRP3 and facilitating NLRP3 inflammasome activation in macrophages.

OsANN4 modulates ROS production and mediates Ca2+ influx in response to ABA.

BACKGROUND: Plant annexins are calcium- and lipid-binding proteins that have multiple functions, and a significant amount of research on plant annexins has been reported in recent years. However, the functions of annexins in diverse biological processes in rice are largely unclear. RESULTS: Herein, we report that OsANN4, a calcium-binding rice annexin protein, was induced by abscisic acid (ABA). Under ABA treatment, the plants in which OsANN4 was knocked down by RNA interference showed some visible phenotypic changes compared to the wild type, such as a lower rooting rate and shorter shoot and root lengths. Moreover, the superoxide dismutase (SOD) and catalase (CAT) activities of the RNAi lines were significantly lower and further resulted in higher accumulation of O2.- and H2O2 than those of the wild-type. A Non-invasive Micro-test Technology (NMT) assay showed that ABA-induced net Ca2+ influx was inhibited in OsANN4 knockdown plants. Interestingly, the phenotypic differences caused by ABA were eliminated in the presence of LaCl3 (Ca2+ channel inhibitor). Apart from this, we demonstrated that OsCDPK24 interacted with and phosphorylated OsANN4. When the phosphorylated serine residue of OsANN4 was substituted by alanine, the interaction between OsANN4 and OsCDPK24 was still observed, however, both the conformation of OsANN4 and its binding activity with Ca2+ might be changed. CONCLUSIONS: OsANN4 plays a crucial role in the ABA response, partially by modulating ROS production, mediating Ca2+ influx or interacting with OsCDPK24.

Protein Phosphatase 2A B'α and B'ß Protect Centromeric Cohesion during Meiosis I.

During meiosis, the stepwise release of sister chromatid cohesion is crucial for the equal distribution of genetic material to daughter cells, enabling generation of fertile gametophytes. However, the molecular mechanism that protects centromeric cohesion from release at meiosis I is unclear in Arabidopsis (Arabidopsis thaliana). Here, we report that the protein phosphatase 2A regulatory subunits B'α and B'ß participate in the control of sister chromatid separation. The double mutant b'αß exhibited severe male and female sterility, caused by the lack of a nucleus or presence of an abnormal nucleus in mature microspores and embryo sacs. 4',6-Diamidino-2-phenylindole staining revealed unequal amounts of DNA in the mononuclear microspores. Transverse sections of the anthers revealed unevenly sized tetrads with or without a nucleus, suggesting a defect in meiocyte meiosis. An analysis of chromosome spreads showed that the sister chromatids separated prematurely at anaphase I in b'αß Immunoblotting showed that AtRECOMBINATION DEFECTIVE8 (AtREC8), a key member of the cohesin complex, was hyperphosphorylated in b'αß anthers and pistils during meiosis but hypophosphorylated in the wild type. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation assays showed that B'α and B'ß interact specifically with AtREC8, AtSHUGOSHIN1 (AtSGO1), AtSGO2, and PATRONUS1. Given that B'α was reported to localize to the centromere in meiotic cells, we propose that protein phosphatase 2A B'α and B'ß are recruited by AtSGO1/2 and PATRONUS1 to dephosphorylate AtREC8 at the site of centromere cohesion to shield it from cleavage until anaphase II, contributing to the balanced separation of sister chromatids at meiosis.

[Study on therapeutic effect of Chaiyin Particles on combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome based on regulation of immune function].

According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P<0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P<0.05, P<0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P<0.01). In vitro results showed that TC_(50), TC_0, IC_(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.

[Therapeutic effect of Compound Qinlan Oral Liquid on treating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

The aim of this paper was to investigate the therapeutic effect of Compound Qinlan Oral Liquid recommended by Provincial Novel Coronary Virus Pneumonia Treatment Scheme on the treatment of BALB/c mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome and to explore its clinical application in the treatment of novel coronavirus pneumonia, and to provide laboratory data support for clinical Chinese medicine. According to the classification of syndromes of novel coronavirus pneumonia by the national competent department of traditional Chinese medicine, this study determined that human coronavirus 229 E(HCoV-229 E)-infected mouse model of cold and dampness syndrome can be used to study human coronavirus pneumonia combined with pestilence attacking the lung syndrome model. This model is suitable for simulating traditional Chinese medicine treatment of common disease syndromes in Novel Coronavirus Pneumonia Diagnosis and Treatment program(trial implementation of the sixth edition). Specific steps are as follows. BALB/c mice of cold and dampness syndrome is infected with HCoV-229 E virus, and were divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), and Compound Qilan Oral Liquid high dose group(22 mL·kg~(-1)·d~(-1)) and low dose group(11 mL·kg~(-1)·d~(-1)). On the day of infection, the Compound Qilan Oral Liquid was administered for three consecutive days. On the last dosing day, the lung tissue was dissected, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted and the HCoV-229 E virus load was detected by RT-PCR. Blood leukocytes were separated and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted and the contents of IL-6, IL-10, TNF-α and IFN-γ were detected by ELISA. Serum was separated and the contents of gastrin(GAS) and motilin(MTL) were detected by ELISA. Histopathological analysis was performed with lung tissue. The high and low doses of Compound Qinlan Oral Liquid significantly reduced the lung index(P<0.01) of mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, and the inhibition rates were 59.01% and 47.72%, respectively. Compared with the model control group, the high and low doses of Compound Qinlan Oral Liquid significantly reduced lung tissue viral load(P<0.01), increased cross blood CD4~+ T lymphocytes, CD8~+ T lymphocytes and total B lymphocyte percentage(P<0.01), reduced serum motilin content(P<0.01), reduced IL-6, IL-10, TNF-α and IFN-γ levels in lungs(P<0.01) and reduced lung tissue inflammation. Compound Qinlan Oral Liquid has a better effect on the mouse model with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, which may attribute to its function of in virus replication inhibition, gastrointestinal function improvement, immunity enhancement, and inflammatory factor reduction.

AtCaM4 interacts with a Sec14-like protein, PATL1, to regulate freezing tolerance in Arabidopsis in a CBF-independent manner.

Calmodulin (CaM), a multifunctional Ca2+ sensor, mediates multiple reactions involved in regulation of plant growth and responses to environmental stress. In this study, we found that AtCaM4 plays a negative role in freezing tolerance in Arabidopsis. The deletion of AtCaM4 resulted in enhanced freezing tolerance in cam4 mutant plants. Although AtCaM4 and AtCaM1 were cold-induced isoforms, cam4/cam1Ri double-mutant and cam4 single-mutant plants exhibited similar improvements in freezing tolerance, indicating that AtCaM4 plays major role. Furthermore, we found that AtCaM4 may influence freezing tolerance in a C-repeat binding factor (CBF)-independent manner as cold-induced expression patterns of CBFs did not change in the cam4/cam1Ri mutant. In addition, among the cold-responsive (COR) genes detected, KIN1, COR15b, and COR8.6 exhibited clearly enhanced expression over the long term in cam4/cam1Ri mutant plants exposed to cold stress. Using immunoprecipitation and mass spectrometry, we identified multiple candidate AtCaM4-interacting proteins. Co-immunoprecipitation assays confirmed the interaction of AtCaM4 with PATL1 in vivo and a phenotype analysis showed that patl1 mutant plants exhibited enhanced freezing tolerance. Thus, we conclude that AtCaM4 negatively regulates freezing tolerance in Arabidopsis by interacting with the novel CaM-binding protein PATL1.

Comparative Study of Early Cold-Regulated Proteins by Two-Dimensional Difference Gel Electrophoresis Reveals a Key Role for Phospholipase Dα1 in Mediating Cold Acclimation Signaling Pathway in Rice.

To understand the early signaling steps that regulate cold responses in rice, two-dimensional difference gel electrophoresis (2-D DIGE)(1)was used to study early cold-regulated proteins in rice seedlings. Using mass spectrometry, 32 spots, which represent 26 unique proteins that showed an altered expression level within 5 min of cold treatment were identified. Among these proteins, Western blot analyses confirmed that the cellular phospholipase D α1 (OsPLDα1) protein level was increased as early as 1 min after cold treatment. Genetic studies showed that reducing the expression ofOsPLDα1makes rice plants more sensitive to chilling stress as well as cold acclimation increased freezing tolerance. Correspondingly, cold-regulated proteomic changes and the expression of the cold-responsive C repeat/dehydration-responsive element binding 1 (OsDREB1) family of transcription factors were inhibited in thepldα1mutant. We also found that the expression ofOsPLDα1is directly regulated by OsDREB1A. This transcriptional regulation ofOsPLDα1could provide positive feedback regulation of the cold signal transduction pathway in rice. OsPLDα1 hydrolyzes phosphatidylcholine to produce the signal molecule phosphatidic acid (PA). By lipid-overlay assay, we demonstrated that the rice cold signaling proteins, MAP kinase 6 (OsMPK6) and OsSIZ1, bind directly to PA. Taken together, our results suggest that OsPLDα1 plays a key role in transducing cold signaling in rice by producing PA and regulatingOsDREB1s' expression by OsMPK6, OsSIZ1, and possibly other PA-binding proteins.

OsBRI1 Activates BR Signaling by Preventing Binding between the TPR and Kinase Domains of OsBSK3 via Phosphorylation.

Many plant receptor kinases transduce signals through receptor-like cytoplasmic kinases (RLCKs); however, the molecular mechanisms that create an effective on-off switch are unknown. The receptor kinase BR INSENSITIVE1 (BRI1) transduces brassinosteroid (BR) signal by phosphorylating members of the BR-signaling kinase (BSK) family of RLCKs, which contain a kinase domain and a C-terminal tetratricopeptide repeat (TPR) domain. Here, we show that the BR signaling function of BSKs is conserved in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) and that the TPR domain of BSKs functions as a "phospho-switchable" autoregulatory domain to control BSKs' activity. Genetic studies revealed that OsBSK3 is a positive regulator of BR signaling in rice, while in vivo and in vitro assays demonstrated that OsBRI1 interacts directly with and phosphorylates OsBSK3. The TPR domain of OsBSK3, which interacts directly with the protein's kinase domain, serves as an autoinhibitory domain to prevent OsBSK3 from interacting with bri1-SUPPRESSOR1 (BSU1). Phosphorylation of OsBSK3 by OsBRI1 disrupts the interaction between its TPR and kinase domains, thereby increasing the binding between OsBSK3's kinase domain and BSU1. Our results not only demonstrate that OsBSK3 plays a conserved role in regulating BR signaling in rice, but also provide insight into the molecular mechanism by which BSK family proteins are inhibited under basal conditions but switched on by the upstream receptor kinase BRI1.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways.

The pathogenesis of Parkinson's disease (PD) often involves the over-activation of microglia. Over-activated microglia could produce several inflammatory mediators, which trigger excessive inflammation and ultimately cause dopaminergic neuron damage. Anti-inflammatory effects of glucagon-like peptide-2 (GLP-2) in the periphery have been shown. Nonetheless, it has not been illustrated in the brain. Thus, in this study, we aimed to understand the role of GLP-2 in microglia activation and to elucidate the underlying mechanisms. BV-2 cells were pretreated with GLP-2 and then stimulated by lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α); the related signaling pathways were evaluated by Western blotting. The rescue effect of GLP-2 on microglia-mediated neurotoxicity was also examined. The results showed that GLP-2 significantly reduced LPS-induced production of inducible nitric oxide synthase (iNOS), cyclooxygenase-s (COX-2), IL-1ß, IL-6 and TNF-α. Blocking of Gαs by NF449 resulted in a loss of this anti-inflammatory effect in BV-2 cells. Analyses in signaling pathways demonstrated that GLP-2 reduced LPS-induced phosphorylation of ERK1/2, JNK1/2 and p65, while no effect was observed on p38 phosphorylation. In addition, GLP-2 could suppress microglia-mediated neurotoxicity. All results imply that GLP-2 inhibits LPS-induced microglia activation by collectively regulating ERK1/2, JNK1/2 and p65.

MicroRNA expression profiles and networks in mouse lung infected with H1N1 influenza virus.

Influenza A viruses can cause localized outbreaks and worldwide pandemics, owing to their high transmissibility and wide host range. As such, they are among the major diseases that cause human death. However, the molecular changes induced by influenza A virus infection in lung tissue are not entirely clear. Changes in microRNA (miRNA) expression occur in many pathological and physiological processes, and influenza A virus infection has been shown to alter miRNA expression in cultured cells and animal models. In this study, we mined key miRNAs closely related to influenza A virus infection and explored cellular regulatory mechanisms against influenza A virus infection, by building networks among miRNAs and genes, gene ontologies (GOs), and pathways. In this study, miRNAs and mRNAs induced by H1N1 influenza virus infection were measured by gene chips, and we found that 82 miRNAs and 3371 mRNAs were differentially expressed. The 82 miRNAs were further analyzed with the series test of cluster (STC) analysis. Three of the 16 cluster profiles identified by STC, which include 46 miRNAs in the three profiles, changed significantly. Using potential target genes of the 46 miRNAs, we looked for intersections of these genes with 3371 differentially expressed mRNAs; 719 intersection genes were identified. Based on the GO or KEGG databases, we attained GOs or pathways for all of the above intersection genes. Fisher's and χ (2) test were used to calculate p value and false discovery rate (FDR), and according to the standard of p < 0.001, 241 GOs and 76 pathways were filtered. Based on these data, miRNA-gene, miRNA-GO, and miRNA-pathway networks were built. We then extracted three classes of GOs (related to inflammatory and immune response, cell cycle, proliferation and apoptosis, and signal transduction) to build three subgraphs, and pathways strictly related with H1N1 influenza virus infection were filtered to extract a subgraph of the miRNA-pathway network. Last, according to the pathway analysis and miRNA-pathway network analysis, 17 miRNAs were found to be associated with the "influenza A" pathway. This study provides the most complete miRNAome profiles, and the most detailed miRNA regulatory networks to date, and is the first to report the most important 17 miRNAs closely related with the pathway of influenza A. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology and the use of mice as a model for human H1N1 influenza virus infection studies.

Coexistence of a novel KPC-2-encoding MDR plasmid and an NDM-1-encoding pNDM-HN380-like plasmid in a clinical isolate of Citrobacter freundii.

OBJECTIVES: The objective of this study was to characterize the molecular mechanism of coproduction of KPC-2 and NDM-1 in Citrobacter freundii. METHODS: C. freundii strain 112298 was isolated from a human case of septic shock in a Chinese teaching hospital. The major carbapenemase and ESBL genes were detected by PCR. The MIC values were determined by using VITEK 2 and antimicrobial susceptibility was judged by CLSI standards. The resistance plasmid was transferred into Escherichia coli by electroporation, followed by plasmid DNA isolation from the electroporant, and then fully sequenced and compared with closely related plasmids. RESULTS: Strain 112298 produces KPC-2 and NDM-1, encoded by the novel non-typeable plasmid p112298-KPC and an IncX3-type plasmid p112298-NDM, respectively. In p112298-KPC, a Tn1722-based blaKPC-2-carrying transposon is associated with several additional resistance modules, constituting a single MDR region. Assembly of these resistance modules is likely mediated by homologous recombination between five copies of IS26 elements at different sites within the MDR region. p112298-NDM is a very close relation of pNDM-HN380. blaNDM-1 in p112298-NDM is carried by a Tn125 variant, which differs from the prototype Tn125 as observed in pNDM-BJ01 by disruption of an upstream copy of ISAba125 by IS5 and absence of a downstream copy of ISAba125. CONCLUSIONS: Production of KPC-2 and NDM-1 by p112298-KPC and p112298-NDM, respectively, makes C. freundii 112298 highly resistant to carbapenems and, moreover, these two plasmids still harbour genes for resistance to cephalosporins, chloramphenicol, chromate, fosfomycin, quaternary ammonium, rifampicin and sulphonamides.