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Abstract Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls from public GEO databases GSE19151 and GSE48000. We used machine learning to identify essential genes and constructed a diagnostic model for VTE using multivariate logistic regression. Unsupervised cluster analysis revealed a marked difference between m6A modification patterns in terms of immune cell infiltration, inflammatory reactivity, and autophagy. We identified two m6A-related autophagy genes (i.e., CHMP2B and SIRT1) and the crucial m6A regulator YTHDF3 using bioinformatics. We also examined two potential mechanisms through which YTHDF3 may affect VTE. m6A modification, immunity, and autophagy are closely linked in VTE, offering novel mechanistic and therapeutic insights.

This paper proposes a novel phase-based short-term traffic flow prediction method based on parallel multi-task learning for isolated intersections. Different from traditional short-term traffic flow prediction methods, we take the traffic flow of each phase as the minimum prediction unit, instead of directly utilising the traffic flow of a single lane with large random fluctuations. Meanwhile, we design a novel encoding and decoding structure whereby external influencing factors have been incorporated both into encoding and decoding operations. Furthermore, a fusion strategy is proposed to predict the traffic flow of each phase by integrating the traffic flows of lanes whose right of way are provided by the phase. In the fusion strategy, we develop a parallel multi-task prediction framework whereby a new loss function is defined to improve the prediction accuracy. Finally, the proposed method is tested with the traffic flow data collected from an intersection of South Changsheng Road located in the city of Jiaxing. The findings illustrate that the proposed method can achieve better prediction results at different sampling time scales, compared to the existing short-term traffic flow prediction methods.

Abstract Immunotherapy is showing good potential for colorectal cancer therapy, however, low responsive rates and severe immune‐related drug side effects still hamper its therapeutic effectiveness. Herein, a highly stable cerasomal nano‐modulator (DMC@P‐Cs) with ultrasound (US)‐controlled drug delivery capability for selective sonodynamic‐immunotherapy is fabricated. DMC@P‐Cs’ lipid bilayer is self‐assembled from cerasome‐forming lipid (CFL), pyrophaeophorbid conjugated lipid (PL), and phospholipids containing unsaturated chemical bonds (DOPC), resulting in US‐responsive lipid shell. Demethylcantharidin (DMC) as an immunotherapy adjuvant is loaded in the hydrophilic core of DMC@P‐Cs. With US irradiation, reactive oxygen species (ROS) can be effectively generated from DMC@P‐Cs, which can not only kill tumor cells for inducing immunogenic cell death (ICD), but also oxidize unsaturated phospholipids‐DOPC to change the permeability of the lipid bilayers and facilitate controlled release of DMC, thus resulting in down‐regulation of regulatory T cells (Tregs) and amplification of anti‐tumor immune responses. After intravenous injection, DMC@P‐Cs can efficiently accumulate at the tumor site, and local US treatment resulted in 94.73% tumor inhibition rate. In addition, there is no detectable systemic toxicity. Therefore, this study provides a highly stable and US‐controllable smart delivery system to achieve synergistical sonodynamic‐immunotherapy for enhanced colorectal cancer therapy.

Abstract. Background:. As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin. Methods:. Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses. Results:. Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera (Enterobacter and Enterococcus) are unaffected by rifaximin therapy. Conclusions:. IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin. Registration:. Chinese Clinical Trial Registry, ChiCTR1800017911.

Efficient and accurate segmentation of sea ice floes from high-resolution optical (HRO) remote sensing images is crucial for understanding of sea ice evolutions and climate changes, especially in coping with the large data volume. Existing methods suffer from noise interference and the mixture of water and ice caused high segmentation error and less robustness. In this article, we propose a novel sea ice floe segmentation algorithm from HRO images based on texture-sensitive superpixeling and two-stage thresholding. First, sparse components are extracted from the HRO images using the robust principal component analysis (RPCA), and noise is removed by the bilateral filter. The enhanced image is obtained by combining the low-rank matrix and the sparse components. Second, a texture-sensitive simple linear iterative clustering (SLIC) superpixel algorithm is introduced for presegmentation of the enhanced HRO image. Third, a learning-based adaptive thresholding in the two stages is employed to generate the refined segmentation from the derived superpixels blocks. The efficacy of the proposed method is validated on two HRO images using visual assessment, quantitative evaluation (with seven metrics), and histogram comparison. The superior performance of the proposed method has demonstrated its efficacy for sea ice floe segmentation.

Viruses are increasingly viewed as vital components of the human gut microbiota, while their roles in health and diseases remain incompletely understood. Here, we first sequenced and analyzed the 37 metagenomic and 18 host metabolomic samples related to irritable bowel syndrome (IBS) and found that some shifted viruses between IBS and controls covaried with shifted bacteria and metabolites. Especially, phages that infect beneficial lactic acid bacteria depleted in IBS covaried with their hosts. We also retrieved public whole-genome metagenomic datasets of another four diseases (type 2 diabetes, Crohn’s disease, colorectal cancer, and liver cirrhosis), totaling 438 samples including IBS, and performed uniform analysis of the gut viruses in diseases. By constructing disease-specific co-occurrence networks, we found viruses actively interacting with bacteria, negatively correlated with possible dysbiosis-related and inflammation-mediating bacteria, increasing the connectivity between bacteria modules, and contributing to the robustness of the networks. Functional enrichment analysis showed that phages interact with bacteria through predation or expressing genes involved in the transporter and secretion system, metabolic enzymes, etc. We further built a viral database to facilitate systematic functional classification and explored the functions of viral genes on interacting with bacteria. Our analyses provided a systematic view of the gut virome in the disease-related microbial community and suggested possible positive roles of viruses concerning gut health.

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder presenting a high comorbidity with depressive disorder (DD). Many studies have confirmed that these two disease share the similar pathophysiological process, but evidence of the genetic risks is limited. This study aimed to analyze the genetic susceptibilities for IBS and DD in Chinese patients. Pooled whole-exome sequencing (pooled-WES) was performed to identify the candidate variants in the group of diarrhea predominant IBS (IBS-D) patients, DD patients, and healthy controls (HC). Then, targeted sequencing was used to validate the candidate variants in three additional cohorts of IBS-D, DD, and HC. Four variants associated with both IBS-D and DD were identified through pooled-WES, and three of them were validated in targeted sequencing. SYT8 rs3741231 G allele and SSPO rs12536873 TT genotype were associated with both IBS-D and DD. The genes of these variants are important in neurogenesis and neurotransmission. In addition, we found COL6A1 rs13051496, a unique risk variation for IBS-D. It increased the IBS-D risk and had a positive correlation with the scores of abdominal bloating and dissatisfaction of bowel habits. Through the results of this study, it provides a genetic basis for the high comorbidity of IBS-D and DD. Keywords: Irritable bowel syndrome, Depressive disorder, Pooled-sequencing, Whole-exome sequencing, Genetic susceptibilities

Biofilm formation by Vibrio cholerae is regulated by c-di-GMP and requires the type IV MSHA pilus. Here, Floyd et al. show that the MSHA pilus is a dynamic system, and that both extension and retraction are directly controlled by c-di-GMP via regulation of activity of the extension ATPase MshE.

Antibiotics are commonly overused to prevent livestock from diseases and to increase production performance. As potential substitutes of antibiotics, plant extracts have attracted the attention of researchers. It was known to all that addition of Macleaya cordata extract (MCE) to the food could advance immunity, intestinal health and animal performance. Thus, it was conducted to investigate the influence of MCE (0, 100, 150 and 200 mg/kg, with six replicate pens/treatment and 24 hens/pen) on intestinal morphology and microbial diversity in different intestinal segments in Xuefeng black-boned chicken in this study. The results showed that MCE supplement (100, 150 and 200 mg/kg) significantly diminished (P

Helicobacter pylori uses a cluster of polar, sheathed flagella for swimming motility. A search for homologs of H. pylori proteins that were conserved in Helicobacter species that possess flagellar sheaths but were underrepresented in Helicobacter species with unsheathed flagella identified several candidate proteins. Four of the identified proteins are predicted to form part of a tripartite efflux system that includes two transmembrane domains of an ABC transporter (HP1487 and HP1486), a periplasmic membrane fusion protein (HP1488), and a TolC-like outer membrane efflux protein (HP1489). Deleting hp1486/hp1487 and hp1489 homologs in H. pylori B128 resulted in reductions in motility and the number of flagella per cell. Cryo-electron tomography studies of intact motors of the Δhp1489 and Δhp1486/hp1487 mutants revealed many of the cells contained a potential flagellum disassembly product consisting of decorated L and P rings, which has been reported in other bacteria. Aberrant motors lacking specific components, including a cage-like structure that surrounds the motor, were also observed in the Δhp1489 mutant. These findings suggest a role for the H. pylori HP1486-HP1489 tripartite efflux system in flagellum stability. Three independent variants of the Δhp1486/hp1487 mutant with enhanced motility were isolated. All three motile variants had the same frameshift mutation in fliL, suggesting a role for FliL in flagellum disassembly.

Abstract Background Genetic factors increase the risk of irritable bowel syndrome (IBS). Analysis of single nucleotide polymorphisms (SNPs) has been used in IBS patients, but the findings are inconsistent. The goal of this review was to synthesize all the published SNPs studies of IBS through meta-analysis to objectively evaluate the relevance of SNPs to IBS risks. Methods IBS - related polymorphisms studies from 2000 to 2018 were searched. Pooled odds ratios with a 95% confidence interval for each SNP were evaluated through five genetic models. Ethnicity, ROME criteria and IBS subtypes were defined for subgroup analyze. Results Ten relevant genes were evaluated. SNPs rs4263839 and rs6478108 of TNFSF15 associated with an increased risk of IBS; IL6 rs1800795 increased the risk for Caucasian IBS patients which diagnosed by Rome III criteria; and IL23R rs11465804 increased the risk for IBS-C patients. IL10 rs1800896 GG genotype associated with a decreased risk of IBS. No evidence supported the association of GNβ3 rs5443, TNFα rs1800629, and IL10 rs1800871 to IBS in this study. Conclusions This meta-analysis presents an in-depth overview for IBS SNPs analysis. It was confirmed that polymorphisms of TNFSF15 associated with increased IBS risk, while IL10 rs1800896 associated with decreased IBS risk. It might offer some insights into polymorphisms of inflammation factors which might affect IBS susceptibility. Moreover, the analysis also emphasizes the importance of diagnostic criteria and phenotype homogeneity in IBS genetic studies.

Background and AimsIrritable bowel syndrome (IBS) and depression have high tendencies of comorbidity. In particular, diarrhea-predominant IBS (IBS-D) and depression exhibit similar fecal microbiota signatures, yet little is known about their pathogenic mechanism. Here, we propose that the differences in structure and composition of IBS-D and depression gut microbiota give rise to different downstream functions, which lead to distinct clinical phenotypes via host metabolism and further influence the interaction of brain–gut axis.MethodsWe performed multiomics study, including fecal metagenome-wide sequencing and serum metabolomics profiling in 65 individuals with IBS-D (n=22), depression (n=15), comorbid patients (n=13), and healthy controls (n=15). We analyzed functional genes contributed by the primary genus and evaluated their correlations with clinical indices and host metabolites.ResultsMetagenomic analysis revealed 26 clusters of orthologous groups of protein (COG) categories consisting of a total of 4,631 functional genes. Trehalose and maltose hydrolase (COG1554) and fucose permease (COG0738) were the most relevant and enriched functional genes in the IBS-D patients; urease accessory proteins UreE (COG2371) was that in the depression patients. Context based genome annotation suggest that an alteration of Escherichia coli and Enterobacter cloacae in IBS-D and depression respectively may be responsible for the enrichment described above. Correlation with host metabolites, such as maltotriose and isomaltose in carbohydrate metabolism and anandamide in neuroactive metabolism, drew further connections between these findings.ConclusionsThese changes led us to propose a connection between genomic signatures and clinical differences observed in IBS-D and depression. Our findings provide further insights into the involvement of gut microbiota in diseases related to brain–gut disorder.

The bacterial flagellar motor switches rotational direction between counterclockwise (CCW) and clockwise (CW) to direct the migration of the cell. The cytoplasmic ring (C-ring) of the motor, which is composed of FliG, FliM, and FliN, is known for controlling the rotational sense of the flagellum. However, the mechanism underlying rotational switching remains elusive. Here, we deployed cryo-electron tomography to visualize the C-ring in two rotational biased mutants in Vibrio alginolyticus. We determined the C-ring molecular architectures, providing novel insights into the mechanism of rotational switching. We report that the C-ring maintained 34-fold symmetry in both rotational senses, and the protein composition remained constant. The two structures show FliG conformational changes elicit a large conformational rearrangement of the rotor complex that coincides with rotational switching of the flagellum. FliM and FliN form a stable spiral-shaped base of the C-ring, likely stabilizing the C-ring during the conformational remodeling.

Accurately predicting oilfield development indicators (such as oil production, liquid production, current formation pressure, water cut, oil production rate, recovery rate, cost, profit, etc.) is to realize the rational and scientific development of oilfields, which is an important basis to ensure the stable production of the oilfield. Due to existing oilfield development index prediction methods being difficult to accurately reflect the complex nonlinear problem in the oil field development process, using the artificial neural network, which can predict the oilfield development index with the function of infinitely close to any non-linear function, will be the most ideal prediction method at present. This article summarizes four commonly used artificial neural networks: the BP neural network, the radial basis neural network, the generalized regression neural network, and the wavelet neural network, and mainly introduces their network structure, function types, calculation process and prediction results. Four kinds of artificial neural networks are optimized through various intelligent algorithms, and the principle and essence of optimization are analyzed. Furthermore, the advantages and disadvantages of the four artificial neural networks are summarized and compared. Finally, based on the application of artificial neural networks in other fields and on existing problems, a future development direction is proposed which can serve as a reference and guide for the research on accurate prediction of oilfield development indicators.

ABSTRACT Many motile bacteria swim or swarm using a filamentous rotating organelle, the flagellum. FliL, a component protein of the flagellar motor, is known to enhance the motor performance under high-load conditions in some bacteria. Here we determined the structure of the periplasmic region of FliL (FliLPeri) of the polar flagellum of Vibrio alginolyticus. FliLPeri shows a remarkable structural similarity to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain of stomatin family proteins, some of which are involved in modulation of ion channel activities in various organisms. FliLPeri forms a ring assembly in the crystal with an inner diameter of around 8 nm, which is comparable to the size of the stator unit. Mutational analyses suggest that the FliL ring forms a complex with the stator unit and that the length of the periplasmic linkers of FliL and the stator B-subunit is essential for the complex formation. We propose a model of the FliL-stator complex to discuss how Vibrio FliL modulates stator function in the bacterial flagellar motor under conditions of high viscosity. IMPORTANCE Some flagellated bacteria regulate motor torque in response to the external load change. This behavior is critical for survival, but the mechanism has remained unknown. Here, we focused on a key protein, FliL of Vibrio alginolyticus, and solved the crystal structure of its periplasmic region (FliLPeri). FliLPeri reveals striking structural similarity to a conserved domain of stomatin, which is involved in ion channel regulation in some organisms, including mammals. FliLPeri forms a ring with an inner diameter that is comparable in size to the stator unit. The mutational analyses suggested that the presence of the ring-like assembly of FliL around the stator unit enhances the surface swarming of Vibrio cells. Our study data also imply that the structural element for the ion channel regulation is conserved from bacteria to mammals.

Angelicae Sinensis Radix (AS), a well-known herb in traditional Chinese medicine (TCM), has been wildly used for replenishing the blood and promoting circulation, in Asia for thousands of years. It has been confirmed that AS also possesses the pharmacological activity of anti-depression. At the same time, recent studies suggested that depression is associated with anemia, and depression could be ameliorated via modulating the blood system. However, it is still unknown whether the anti-depression effect of AS is related to its pharmacological activity of modulating the blood system. In the current study, hematological examination and metabonomic techniques were performed to explore potential anti-depression mechanisms of AS, related to the function of modulating the blood system in a chronic unpredictable mild stress (CUMS) model. The results demonstrated that AS could significantly improve CUMS-induced depressive symptom, hematological anomalies, and hypoxia symptoms. The analysis of metabonomics demonstrated that 26 potential biomarkers in depression could be regulated by the administration of AS. Among them, eight biomarkers participate in the metabolic pathways of amino acid and sphingolipid, and energy metabolism could also be regulated in an anemia model through the administration of AS, as reported in previous literatures. Further results proved that AS modulated energy metabolism in depression through the inhibition of the expression of pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) and lactate dehydrogenase A (LDHA). These results suggested that the modulation of the blood system was involved in the anti-depression effect of AS. The mechanism may be associated with the promotion of the body’s energy metabolism, the stabilization of cell membranes, the promotion of serum protein synthesis, and the enhancement of immunity.

Novel two-dimensional (2D) materials have received extensive attention in the field of photocatalysis due to their unique properties. Traditional ZnO material with wurtzite structure transforms into a stable graphite-like structure that has the characteristics of 2D material when its thickness is less than a few atomic layers. In this work, using first-principles calculations, we investigated the potential of multilayer graphite-like ZnO as a photocatalyst for water splitting. The results showed that multilayer ZnO is a series of direct bandgap semiconductors, and their band edge positions all straddle the redox potential of water. Increasing with the number of layers, the bandgap of multilayer ZnO decreased from 3.20 eV for one layer to 2.21 eV for six layers, and visible light absorption capacity was significantly enhanced. Hence, multilayer ZnO was indeed promising for photocatalytic water splitting. Furthermore, suitable biaxial tensile strain could decrease the bandgap and maintain the stable graphite-like structure at a broader thickness range. In contrast, excessive biaxial tensile strain could change the redox capacity of multilayer ZnO and prevent it from catalyzing water splitting. Our theoretical results show that six-layer ZnO under 1% biaxial strain had direct bandgap of 2.07 eV and represents the most excellent photocatalytic performance among these multilayer ZnO materials.

Background: Left bundle branch area pacing (LBBAP) includes left bundle branch pacing (LBBP) and left ventricular (LV) septal myocardial pacing (LVSP). Hypothesis: The study aimed to assess resynchronization effects and clinical outcomes by LBBAP in heart failure (HF) patients with cardiac resynchronization therapy (CRT) indications. Methods: LBBAP was successfully performed in 29 consecutive patients and further classified as the LBBP-group (N = 15) and LVSP-group (N = 14) based on the LBBP criteria and novel LV conduction time measurement (LV CT, between LBBAP site and LV pacing (LVP) site). AV-interval optimized LBBP or LVSP, or LVSP combined with LVP (LVSP-LVP) was applied. LV electrical and mechanical synchrony and clinical outcomes were assessed. Results: All 15 patients in the LBBP-group received optimized LBBP while 14 patients in the LVSP-group received either optimized LVSP (5) or LVSP-LVP (9). The LV CT during LBBP was significantly faster than that during LVP (p < .001), while LV CT during LVSP were similar to LVP (p = .226). The stimulus to peak LV activation time (Stim-LVAT, 71.2 ± 8.3 ms) and LV mechanical synchrony (TSI-SD, 35.3 ± 9.5 ms) during LBBP were significantly shorter than those during LVSP (Stim-LVAT 89.1 ± 19.5 ms, TSI-SD 49.8 ± 14.4 ms, both p < .05). Following 17(IQR 8) months of follow-up, the improvement of LVEF (26.0%(IQR 16.0)) in the LBBP-group was significantly greater than that in the LVSP-group (6.0%(IQR 20.8), p = .001). Conclusions: LV activation in LBBP propagated significantly faster than that of LVSP. LBBP generated superior electrical and mechanical resynchronization and better LVEF improvement over LVSP in HF patients with CRT indications. [ABSTRACT FROM AUTHOR]

Objectives Radix Bupleuri-Radix Paeoniae Alba (BP), a traditional Chinese medicine herb pair, has treated depression by coordinating the liver in Chinese classical medicine books and modern research. This study aims to verify the antidepressant effect of BP by behavioural examination, and reveal the underlying antidepressant mechanisms of BP. Methods The antidepressant effects in chronic unpredictable mild stress (CUMS) of BP were observed by behavioural indicators and 1H nuclear magnetic resonance (1H-NMR) and ultra-highperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabonomics techniques combined with the related analysis platforms. Key findings BP could significantly improve the depressive behaviour of CUMS rats. Compared with the model group, body weight (P < 0.05), the number of crossing (P < 0.001) and rearing (P < 0.01) and sucrose preference rate (P < 0.01) were significantly enhanced, and the immobility time was shortened in the forced swimming test (P < 0.001) of the BP group. In metabonomics study, 35 depression-related metabolites were identified by 1H NMR and UHPLC-MS/MS metabonomics by comparing model and control groups. BP could significantly retrieve 17 depression-related metabolites. Thirteen depression-related metabolic pathways were found through Met-PA and BP could regulate seven metabolic pathways. Conclusions BP herb pair had significantly antidepressant effect, which provides a basis for further finding drug targets. [ABSTRACT FROM AUTHOR]

The article focuses on the formation of a multiprotein defense complex on the surface of the gram-negative bacterial pathogen Salmonella enterica serovar Typhimurium (Stm) within human cells. Topics include the role of guanylate-binding proteins (GBPs) in organizing host defense, the molecular details of the defense complex assembly, and its implications for innate immune signaling against bacterial pathogens.

The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through O-GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.

Chemical-induced spores of the Gram-negative bacterium Myxococcus xanthus are peptidoglycan (PG)-deficient. It is unclear how these spherical spores germinate into rod-shaped, walled cells without preexisting PG templates. We found that germinating spores first synthesize PG randomly on spherical surfaces. MglB, a GTPase-activating protein, forms a cluster that responds to the status of PG growth and stabilizes at one future cell pole. Following MglB, the Ras family GTPase MglA localizes to the second pole. MglA directs molecular motors to transport the bacterial actin homolog MreB and the Rod PG synthesis complexes away from poles. The Rod system establishes rod shape de novo by elongating PG at nonpolar regions. Thus, similar to eukaryotic cells, the interactions between GTPase, cytoskeletons, and molecular motors initiate spontaneous polarization in bacteria. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies. The incidence of MDS is gradually increasing, but the pathogenesis is still not very clear. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in both oncogenic and tumor-suppressive pathways. However, the function of lncRNAs in MDS is still unknown. The purpose of this study was to investigate the expression profiles and biological function of the aberrantly expressed lncRNAs and mRNAs in MDS. Methods: We downloaded two data sets (GSE4619 and GSE19429) from the Gene Expression Omnibus database and obtained differentially expressed (DE) lncRNAs and DE-mRNAs between MDS cases and healthy controls. Then we performed systematic bioinformatics analysis to know the biological function of DE-lncRNAs and DEmRNAs in MDS. Results: We identified 40 DE-lncRNAs and 643 DE-mRNAs between MDS cases and healthy controls. Gene Ontology (GO) and pathway analysis revealed that DE-lncRNAs and DE-mRNAs were mainly involved in necroptosis, apoptosis, immunodeficiency, p53 and FoxO signaling pathways. LncRNA-mRNA co-expression and lncRNA functional similarity network showed that twelve down-regulated lncRNAs co-regulated the same target gene and they were similar in function. Conclusions: The comprehensive analysis of lncRNA and mRNA is helpful in understanding the pathogenesis of MDS, and the synergistically down-regulated lncRNAs may contribute to the development of new diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Assembly of pili on the gram-positive bacterial cell wall involves 2 conserved transpeptidase enzymes named sortases: One for polymerization of pilin subunits and another for anchoring pili to peptidoglycan. How this machine controls pilus length and whether pilus length is critical for cell-to-cell interactions remain unknown. We report here in Actinomyces oris, a key colonizer in the development of oral biofilms, that genetic disruption of its housekeeping sortase SrtA generates exceedingly long pili, catalyzed by its pilus-specific sortase SrtC2 that possesses both pilus polymerization and cell wall anchoring functions. Remarkably, the srtA-deficient mutant fails to mediate interspecies interactions, or coaggregation, even though the coaggregation factor CafA is present at the pilus tip. Increasing ectopic expression of srtA in the mutant progressively shortens pilus length and restores coaggregation accordingly, while elevated levels of shaft pilins and SrtC2 produce long pili and block coaggregation by SrtA+ bacteria. With structural studies, we uncovered 2 key structural elements in SrtA that partake in recognition of pilin substrates and regulate pilus length by inducing the capture and transfer of pilus polymers to the cell wall. Evidently, coaggregation requires proper positioning of the tip adhesin CafA via modulation of pilus length by the housekeeping sortase SrtA. [ABSTRACT FROM AUTHOR]

The effect of thermal aging on microstructural evolution and mechanical behavior was investigated via advanced instrumental analysis. The scanning electron microscope (SEM) results demonstrated that the microstructure transformed from martensite into martensite/bainite mixture in the coarse-grained heat-affected zone (CGHAZ) of 16MND5. The micro-hardness in the CGHAZ has a significantly positive correlation with thermal aging time owing to the change of microstructure and the increased number of M23C6 precipitates. Moreover, the tensile strength and elongation of the dissimilar metal welds have a positive correlation with thermal aging time. However, the fracture occurs on the Alloy 152 side and the fracture mode was the ductile fracture.

A multi-analytical approach was used to investigate the effect of thermal aging on the microstructure and mechanical properties of ER308L/Z2CND18.12N2. The results demonstrated that fractures occurred preferentially on the ER308L side. Z2CND18.12N2 exhibited superior fracture toughness compared to ER308L regardless of thermal aging time. The ultimate tensile strength significantly increased from 564.5 MPa in the unaged condition to 592.7 MPa to MPa after thermal aging and the fracture mode changed from ductile fracture into a ductile + quasi-cleavage fracture. The fusion zone (FZ) with the chemical composition gradient was about 40 μm from the Z2CND18.12N2 to ER308L. After thermal aging, spinodal decomposition and G-phase precipitation were observed for the first time in the ferrite phase of the FZ. Moreover, the hardness presented the following trend: FZ > ER308L > Z2CND18.12N2. The hardness of the ferrite phase dramatically increased from 6.13 GPa in an unaged condition to 8.46 GPa in a 10,000 h aged condition.

Vibrio species are Gram-negative rod-shaped bacteria that are ubiquitous and often highly motile in aqueous environments. Vibrio swimming motility is driven by a polar flagellum covered with a membranous sheath, but this sheathed flagellum is not well understood at the molecular level because of limited structural information. Here, we use Vibrio alginolyticus as a model system to study the sheathed flagellum in intact cells by combining cryoelectron tomography (cryo-ET) and subtomogram analysis with a genetic approach. We reveal striking differences between sheathed and unsheathed flagella in V. alginolyticus cells, including a novel ring-like structure at the bottom of the hook that is associated with major remodeling of the outer membrane and sheath formation. Using mutants defective in flagellar motor components, we defined a Vibrio-specific feature (also known as the T ring) as a distinctive periplasmic structure with 13-fold symmetry. The unique architecture of the T ring provides a static platform to recruit the PomA/B complexes, which are required to generate higher torques for rotation of the sheathed flagellum and fast motility of Vibrio cells. Furthermore, the Vibrio flagellar motor exhibits an intrinsic length variation between the inner and the outer membrane bound complexes, suggesting the outer membrane bound complex can shift slightly along the axial rod during flagellar rotation. Together, our detailed analyses of the polar flagella in intact cells provide insights into unique aspects of the sheathed flagellum and the distinct motility of Vibrio species. [ABSTRACT FROM AUTHOR]

The flagellar motor is embedded in the cell envelope and rotates upon interaction between the stator and the rotor. The rotation is powered by ion flow through the stator. A single transmembrane protein named FliL is associated with torque generation in the flagellar motor. We established an Escherichia coli over-expression system for FliL of Vibrio alginolyticus, a marine bacterium that has a sodium-driven polar flagellum. We successfully expressed, purified, and crystallized the ca. 17 kDa full-length FliL protein and generated a construct that expresses only the ca. 14 kDa periplasmic region of FliL (ΔTM FliL). Biochemical characterization and NMR analysis revealed that ΔTM FliL weakly interacted with itself to form an oligomer. We speculate that the observed dynamic interaction may be involved in the role of FliL in flagellar motor function. [ABSTRACT FROM AUTHOR]

The torque of the bacterial flagellum is generated by the rotor-stator interaction coupled with the ion flow through the channel in the stator. Anchoring the stator unit to the peptidoglycan layer with proper orientation around the rotor is believed to be essential for smooth rotation of the flagellar motor. The stator unit of the sodium-driven flagellar motor of Vibrio is composed of PomA and PomB, and is thought to be fixed to the peptidoglycan layer and the T-ring by the C-terminal periplasmic region of PomB. Here, we report the crystal structure of a C-terminal fragment of PomB (PomBc) at 2.0-A resolution, and the structure suggests a conformational change in the N-terminal region of PomBc for anchoring the stator. On the basis of the structure, we designed double-Cys replaced mutants of PomB for in vivo disulfide cross-linking experiments and examined their motility. The motility can be controlled reproducibly by reducing reagent. The results of these experiments suggest that the N-terminal disordered region (121-153) and following the N-terminal two-thirds of α1 (154-164) in PomBc changes its conformation to form a functional stator around the rotor. The cross-linking did not affect the localization of the stator nor the ion conductivity, suggesting that the conformational change occurs in the final step of the stator assembly around the rotor. [ABSTRACT FROM AUTHOR]

In this work, we reported the effects of sputtering power on the structure, optical and electrical properties of InN nanodots prepared on Al2O3 substrate by magnetron sputtering.The results showed that the as-grown InN films exhibited uniform nanodot morphology and the size of the InN nano grains increased with the sputtering power was increased. The InN nanodot exhibited highly c-axis prefered orientation with mainly InN (002) diffraction. The optical band gap of InN samples showed an decreasing trend with the increase in sputteirng power. Moreover, the electrical properties of the InN samples were discussed in detail by hall effect and the carrier concentration and mobility could be adjusted from 3.233×1019 to 1.655×1020 cm-3 and 1.151 to 10.101 cm2/v•s, respectively. These results will lay a good fundation for the applicaion of InN material in the field of gas sensers and light emitting diodes.

Since there is no fixed infrastructure or centralized management in wireless ad hoc networks, a Connected Dominating Set (CDS) has been proposed to serve as a virtual backbone. The CDS of a graph representing a network has a significant impact on the efficient design of routing protocols in wireless networks. This problem has been studied extensively in Unit Disk Graphs (UDG), in which all nodes have the same transmission ranges. However, in practice, the transmission ranges of all nodes are not necessarily equal. In this paper, we model a network as a disk graph and introduce the CDS problem in disk graphs. We present two efficient approximation algorithms to obtain a minimum CDS. The performance ratio of these algorithms is constant if the ratio of the maximum transmission range over the minimum transmission range in the network is bounded, These algorithms can be implemented as distributed algorithms. Furthermore, we show a size relationship between a maximal independent set and a CDS as well as a bound of the maximum number of independent neighbors of a node in disk graphs, The theoretical analysis and simulation results are also presented to verify our approaches. [ABSTRACT FROM AUTHOR]

Lysins are murein hydrolases produced by bacteriophage that act on the bacterial host cell wall to release progeny phage. When added extrinsically in their purified form, these enzymes produce total lysis of susceptible Gram-positive bacteria within seconds, suggesting a unique antimicrobial strategy. All known Gram-positive lysins are produced as a single polypeptide containing a catalytic activity domain, which cleaves one of the four major peptidoglycan bonds, and a cell-wall-binding domain, which may bind a species-specific carbohydrate epitope in the cell wall. Here, we have cloned and expressed a unique lysin from the streptococcal bacteriophage C1, termed PlyC. Molecular characterization of the plyC operon reveals that PlyC is, surprisingly, composed of two separate gene products, PlyCA and PlyCB. Based on biochemical and biophysical studies, the catalytically active PlyC holoenzyme is composed of eight PlyCB subunits for each PlyCA. Inhibitor studies predicted the presence of an active-site cysteine, and bioinformatic analysis revealed a cysteine, histidine-dependent amidohydrolase/peptidase domain within PlyCA. Point mutagenesis confirmed that PlyCA is responsible for the observed catalytic activity, and Cys-333 and His-420 are the active-site residues. PlyCB was found to self-assemble into an octamer, and this complex alone was able to direct streptococcal cell-wall-specific binding. Similar to no other proteins in sequence databases, PlyC defines a previously uncharacterized structural family of cell-wall hydrolases. [ABSTRACT FROM AUTHOR]

The bacterial flagellum is a biological nanomachine that rotates to allow bacteria to swim. For flagellar rotation, torque is generated by interactions between a rotor and a stator. The stator, which is composed of MotA and MotB subunit proteins in the membrane, is thought to bind to the peptidoglycan (PG) layer, which anchors the stator around the rotor. Detailed information on the stator and its interactions with the rotor remains unclear. Here, we deployed cryo-electron tomography and genetic analysis to characterize in situ structure of the bacterial flagellar motor in Vibrio alginolyticus, which is best known for its polar sheathed flagellum and high-speed rotation. We determined in situ structure of the motor at unprecedented resolution and revealed the unique protein-protein interactions among Vibrio-specific features, namely the H ring and T ring. Specifically, the H ring is composed of 26 copies of FlgT and FlgO, and the T ring consists of 26 copies of a MotX-MotY heterodimer. We revealed for the first time a specific interaction between the T ring and the stator PomB subunit, providing direct evidence that the stator unit undergoes a large conformational change from a compact form to an extended form. The T ring facilitates the recruitment of the extended stator units for the high-speed motility in Vibrio species. [ABSTRACT FROM AUTHOR]

Helicobacter pylori uses a cluster of polar, sheathed flagella for motility, which it requires for colonization of the gastric epithelium in humans. As part of a study to identify factors that contribute to localization of the flagella to the cell pole, we disrupted a gene encoding a cardiolipin synthase (clsC) in H. pylori strains G27 and B128. Flagellum biosynthesis was abolished in the H. pylori G27 clsC mutant but not in the B128 clsC mutant. Transcriptome sequencing analysis showed that flagellar genes encoding proteins needed early in flagellum assembly were expressed at wild-type levels in the G27 clsC mutant. Examination of the G27 clsC mutant by cryo-electron tomography indicated the mutant assembled nascent flagella that contained the MS ring, C ring, flagellar protein export apparatus, and proximal rod. Motile variants of the G27 clsC mutant were isolated after allelic exchange mutagenesis using genomic DNA from the B128 clsC mutant as the donor. Genome resequencing of seven motile G27 clsC recipients revealed that each isolate contained the flgI (encodes the P-ring protein) allele from B128. Replacing the flgI allele in the G27 clsC mutant with the B128 flgI allele rescued flagellum biosynthesis. We postulate that H. pylori G27 FlgI fails to form the P ring when cardiolipin levels in the cell envelope are low, which blocks flagellum assembly at this point. In contrast, H. pylori B128 FlgI can form the P ring when cardiolipin levels are low and allows for the biosynthesis of mature flagella. [ABSTRACT FROM AUTHOR]

The bacterial flagellum is a sophisticated self-assembling nanomachine responsible for motility in many bacterial pathogens, including Pseudomonas aeruginosa, Vibrio spp., and Salmonella enterica. The bacterial flagellum has been studied extensively in the model systems Escherichia coli and Salmonella enterica serovar Typhimurium, yet the range of variation in flagellar structure and assembly remains incompletely understood. Here, we used cryo-electron tomography and subtomogram averaging to determine in situ structures of polar flagella in P. aeruginosa and peritrichous flagella in S. Typhimurium, revealing notable differences between these two flagellar systems. Furthermore, we observed flagellar outer membrane complexes as well as many incomplete flagellar subassemblies, which provide additional insight into mechanisms underlying flagellar assembly and loss in both P. aeruginosa and S. Typhimurium. [ABSTRACT FROM AUTHOR]

The bacterial flagellum has evolved as one of the most remarkable nanomachines in nature. It provides swimming and swarming motilities that are often essential for the bacterial life cycle and pathogenesis. Many bacteria such as Salmonella and Vibrio species use flagella as an external propeller to move to favorable environments, whereas spirochetes utilize internal periplasmic flagella to drive a serpentine movement of the cell bodies through tissues. Here, we use cryo-electron tomography to visualize the polar sheathed flagellum of Vibrio alginolyticus with particular focus on a Vibrio-specific feature, the H-ring. We characterized the H-ring by identifying its two components FlgT and FlgO. We found that the majority of flagella are located within the periplasmic space in the absence of the H-ring, which are different from those of external flagella in wild-type cells. Our results not only indicate the H-ring has a novel function in facilitating the penetration of the outer membrane and the assembly of the external sheathed flagella but also are consistent with the notion that the flagella have evolved to adapt highly diverse needs by receiving or removing accessary genes. IMPORTANCE Flagellum is the major organelle for motility in many bacterial species. While most bacteria possess external flagella, such as the multiple peritrichous flagella found in Escherichia coli and Salmonella enterica or the single polar sheathed flagellum in Vibrio spp., spirochetes uniquely assemble periplasmic flagella, which are embedded between their inner and outer membranes. Here, we show for the first time that the external flagella in Vibrio alginolyticus can be changed as periplasmic flagella by deleting two flagellar genes. The discovery here may provide new insights into the molecular basis underlying assembly, diversity, and evolution of flagella. [ABSTRACT FROM AUTHOR]

Well-separated silicon nanoparticles (Si-NPs) were deposited on Si wafer and amorphous carbon micro-grids at room temperature by magnetron sputtering through a nanocluster source. With the introduction of He as a carrier gas in Ar sputtering atmosphere, well-separated Si-NPs with narrow size distribution can be observed by transmission electron microscopy. High resolution transmission electron microscopy study reveals that the average size of the Si-NPs is about 5 nm in diameter. Furthermore, well-crystallized Si-NPs without oxidized layer are of strong photoluminescence with a double-peak structure at the positions of 380 and 398 nm at room temperature. [ABSTRACT FROM AUTHOR]

Black fungus, with high nutritional and medicinal value, has been cultivated in China for a long time, and Heilongjiang alone accounts for about 40% of the global output. At present, the cultivation of black fungus derives mainly from the inheritance of relatively primitive practices and experience of farmers, resulting in inconsistent quality of fungus. In this study, a smart control system for the precision cultivation of black fungus was designed by using intelligent detection and control technology. The system includes a precision culture test environment and remote control system. The precision cultivation environment contains four sub-independent environments. The key parameters such as temperature, humidity, and light behavior were collected and can be adjusted individually, according to the precision cultivation stages. The intelligent remote control system included a controller cabinet, sensors unit, temperature control unit, humidity control unit, light control unit, and information transmitting unit. The controller cabinet includes a key controller which can auto-control the temperature, humidity, and lightly adjust components according to the precision cultivation conditions and processing. The temperature sensors were installed in a 3D array close to the fungus bags about 5 cm in rooms. The light tape was installed on the six walls and also had three colors (Red, Blue, and Green) which could be controlled independently in each room. The control strategy through the analysis of the data collected by all sensors, the current cultivate situation of the cultivation environment was obtained, and the heater, fan, light, and nozzle were regulated according to the strategy to maintain a suitable precision cultivation environment for fungus. To verify the feasibility of the precision cultivation processing and control system, the test result shows that the error of temperature control was about 0°C-1°C, the error of humidity control was about 1%-4%, and the error of illuminance control was about 0-50 lx; All the verification results show that the control system for precision cultivation has high precision and can meet the needs of exploring the "Black 29" fungus cultivation experiment environment. Based on the orthogonal experiment, the best combination of the temperature and humidity for each growth stage was also investigated in this study, further proving the reliability and feasibility of the control system for the precision cultivation of Auricularia auricula. [ABSTRACT FROM AUTHOR]

C[sub 1], a lytic bacteriophage infecting group C streptococci, is one of the earliest-isolated phages, and the method of bacterial classification known as phage typing was defined by using this bacteriophage. We present for the first time a detailed analysis of this phage by use of electron microscopy, protein profiling, and complete nucleotide sequencing. This virus belongs to the Podoviridae family of phages, all of which are characterized by short, noncontractile tails. The C[sub 1] genome consists of a linear double-stranded DNA molecule of 16,687 nucleotides with 143-bp inverted terminal repeats. We have assigned functions to 9 of 20 putative open reading frames based on experimental substantiation or bioinformatic analysis. Their products include DNA polymerase, holin, lysin, major capsid, head-tail connector, neck appendage, and major tail proteins. Additionally, we found one intron belonging to the HNH endonuclease family interrupting the apparent lysin gene, suggesting a potential splicing event yielding a functional lytic enzyme. Examination of the C[sub 1] DNA polymerase suggests that this phage utilizes a protein-primed mechanism of replication, which is prominent in the φ29-like members of Podoviridae. Consistent with this evidence, we experimentally determined that terminal proteins are covalently attached to both 5' termini, despite the fact that no homology to known terminal proteins could be elucidated in any of our open reading frames. Likewise, comparative genomics revealed no close evolutionary matches, suggesting that the C[sub 1] bacteriophage is a unique member of the Podoviridae. [ABSTRACT FROM AUTHOR]

Over the past decade, thousands of long noncoding RNAs (lncRNAs) have been identified, many of which play crucial roles in normal physiology and human disease. LncRNAs can interact with chromatin and then recruit protein complexes to remodel chromatin states, thus regulating gene expression. However, how lncRNA-chromatin interactions contribute to their biological functions is largely unknown. Here, we collected and constructed an atlas of 188,647 lncRNA-chromatin interactions in human and mouse. All lncRNAs showed diverse epigenetic modification patterns at their binding sites, especially the marks of enhancer activity. Functional analysis of lncRNA target genes further revealed that lncRNAs could exert their functions by binding to both promoter and distal regulatory elements, especially the distal regulatory elements. Intriguingly, many important pathways were observed to be widely regulated by lncRNAs through distal binding. For example, NEAT1, a cancer lncRNA, controls 13.3% of genes in the PI3K-AKT signaling pathway by interacting with distal regulatory elements. In addition, "two-gene" signatures composed of a lncRNA and its distal target genes, such as HOTAIR-CRIM1, provided significant clinical benefits relative to the lncRNA alone. In summary, our findings underscored that lncRNA-distal interactions were essential for lncRNA functions, which would provide new clues to understand the molecular mechanisms of lncRNAs in complex disease. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a bacterial pathogen that can cause many gastrointestinal diseases, including ulcers and gastric cancer. A unique chemotaxis-mediated motility is critical for H. pylori to colonize in the human stomach and to establish chronic infection, but the underlying molecular mechanisms are not well understood. Here, we employ cryo-electron tomography (cryo-ET) to reveal detailed structures of the H. pylori cell envelope, including the sheathed flagella and chemotaxis arrays. Notably, H. pylori possesses a distinctive periplasmic cage-like structure with 18-fold symmetry. We propose that this structure forms a robust platform for recruiting 18 torque generators, which likely provide the higher torque needed for swimming in high-viscosity environments. We also reveal a series of key flagellar assembly intermediates, providing structural evidence that flagellar assembly is tightly coupled with the biogenesis of the membrane sheath. Finally, we determine the structure of putative chemotaxis arrays at the flagellar pole, which have implications for how the direction of flagellar rotation is regulated. Together, our pilot cryo-ET studies provide novel structural insights into the unipolar flagella of H. pylori and lay a foundation for a better understanding of the unique motility of this organism. [ABSTRACT FROM AUTHOR]

This paper presents a unified view of interestingness measures for interesting pattern discovery. Specifically, we first provide three necessary conditions for interestingness measures being used for association pattern discovery. Then, we reveal one desirable property for interestingness measures: the support-ascending conditional antimonotone property (SA-CAMP). Along this line, we prove that the measures possessing SA-CAMP are suitable for pattern discovery if the itemset-traversal structure is defined by a support-ascending set enumeration tree. In addition, we provide a thorough study on the family of the generalized mean (GM) measure and show their appealing properties, which are exploited for developing the GMiner algorithm for finding interesting association patterns. Finally, experimental results show that GMiner can efficiently identify interesting patterns based on SA-CAMP of the GM measure, even at an extremely low level of support.