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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.