Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Isolation and characterization of intestinal bacteria associated with cellulose degradation in grasshoppers (Orthoptera).

Insect gut bacteria play an essential role in the nutritional metabolism, growth, and development of insects. Grasshoppers (Orthoptera) are cellulose-rich plant-feeding pests. Although the biological potential of grasshopper gut microorganisms to assist cellulose decomposition is well established, microbial resources for efficient degradation of cellulose biomass are still scarce and need to be developed. In this study, we used selective media to isolate cellulose-degrading bacteria from the intestines of Atractomorpha sinensis, Trilophidia annulata, Sphingonotus mongolicus, and Calliptamus abbreviatus. Phylogenetic analysis based on the maximum likelihood method using 16S rDNA sequencing sequences to identify bacteria revealed the isolation of 11 strains belonging to 3 genera, including Klebsiella, Aeromonas, and Bacillus. The degradability of the isolates to cellulose was then determined by the DNS colorimetric method, and the results showed that Bacillus had the highest degradation rate. The elucidation of microbial cellulose degradation capacity in grasshoppers not only contributes to the understanding of multiple plant-insect-microbe interactions, but also provides a valuable microbial resource for solving the biomass conversion of cellulose species problem.

An electrochemical ratiometric biosensor for the detection of dopamine based on an MXene-Au nanocomposite.

Compared with single signal detection, a ratiometric biosensor could offer more accurate and reliable results. Here, a ratiometric electrochemical biosensor for the sensitive and accurate detection of dopamine was developed based on the strong adsorption ability of MXene-Au toward methylene blue, an inner reference element. This ratiometric sensing strategy opened up a new avenue for the development of a ratiometric platform.

E2F family play important roles in tumorigenesis.

Tumors are serious threats to human health. The transcription factors are regarded as the potential targets for tumor treatment. As an important family of transcription factors, E2F family transcription factors (E2Fs) play vital roles in cell proliferation and regulation. However, the expression feature, gene functions, and molecular interactions of E2Fs in tumorigenesis are not clear. In this study, the transcriptome data, mutation data, and protein-protein interaction data of 10 high-incidence tumors in China from the TCGA database were integrated and analyzed to explore the expression, structure, function, mutation, and phylogenetic characteristics of E2Fs. The results showed that E2F1 and E2F7 were regularly upregulated in the tumor samples. Moreover, E2Fs participated in the regulation of the cell cycle, cell aging, and other signaling pathways. As an important regulator, E2F1 interacted with more proteins than other E2Fs. At the same time, the genetic mutation types of E2Fs varied in tumor type and patient sex, of which gene amplification accounts for the largest proportion. Phylogenetic analysis showed that E2Fs were conserved in 41 species, including fruit flies, nematodes, and humans. Meanwhile, E2Fs had a tendency for gene expansion during evolution. In conclusion, this study clarified the expression pattern, mutation characteristics, and evolutionary trend of E2Fs in high-incidence tumors in China, and suggested that E2F family transcription factors could be novel diagnostic markers for tumor diseases. Furthermore, this work can provide a theoretical basis for the development of anti-tumor-targeted drugs.

Cloning and functional analysis of RADIALIS-like 1 gene from Antirrhinum majus.

MYB is one of the largest transcription factor families in plants. Among them, the R3-MYB transcription factor RADIALIS (RAD) plays a very important role in the flowers development in Antirrhinum majus. In this study, a R3-MYB gene similar to RAD was found by analyzing the genome of A. majus, which was named AmRADIALIS-like 1 (AmRADL1). The gene function was predicted through bioinformatics. The relative expression levels in different tissues and organs of wild-type A. majus were analyzed by qRT-PCR. AmRADL1 was overexpressed in A. majus, and the transgenic plants were analyzed by morphological observation and histological staining. The results showed that the open reading frame (ORF) of AmRADL1 gene was 306 bp in length, encoding 101 amino acids. It has typical SANT domain, and the C-terminal contains a CREB motif, which was highly homologous to tomato SlFSM1. The results of qRT-PCR showed that AmRADL1 was expressed in roots, stems, leaves and flowers, and the expression level was higher in flowers. Further analysis of its expression in different floral organs showed that AmRADL1 had the highest expression in carpel. The results of histological staining analysis of the transgenic plants showed that compared with the wild type, although the size of the carpel cells of the transgenic plants did not change significantly, the placenta area in the carpel became smaller and the number of cell decreased. In summary, AmRADL1 may be involved in the regulation of carpel development, but the specific mechanism of action in carpel remains to be further studied.

Increased yield of 2-O-α-d-glucopyranosyl-l-ascorbic acid synthesis by α-glucosidase using rational design that regulating the ground state of enzyme and substrate complex.

BACKGROUND: α-Glucosidase (AG) is a bifunctional enzyme, it has a capacity to synthesize 2-O-α-d-glucopyranosyl-l-ascorbic acid (AA-2G) from l-ascorbic acid (L-AA) and low-cost maltose under mild conditions, but it can also hydrolyze AA-2G, which leads to low synthesis efficiency of AA-2G. MAIN METHODS AND MAJOR RESULTS: This study introduces a rational molecular design strategy to regulate enzymatic reactions based on inhibiting the formation of ground state of enzyme-substrate complex. Y215 was analyzed as the key amino acid site affecting the affinity of AG to AA-2G and L-AA. For the purpose of reducing the hydrolysis efficiency of AA-2G, the mutant Y215W was obtained by analyzing the molecular docking binding energy and hydrogen bond formation between AG and the substrates. Compared with the wild-type, isothermal titration calorimetry (ITC) results showed that the equilibrium dissociation constant (KD ) of the mutant for AA-2G was doubled; the Michaelis constant (Km ) for AA-2G was reduced by 1.15 times; and the yield of synthetic AA-2G was increased by 39%. CONCLUSIONS AND IMPLICATIONS: Our work also provides a new reference strategy for the molecular modification of multifunctional enzymes and other enzymes in cascade reactions system.

A Clinical and Anatomical Study on the Localization of the Temporal Branch of the Facial Nerve Crossing the Zygomatic Arch / Estudio Clínico y Anatómico sobre la Localización del Ramo Temporal del Nervio Facial que Cruza el Arco Cigomático

SUMMARY: To clarify the path of the temporal branch of facial nerve (TB) crossing the zygomatic arch (ZA). Eighteen fresh adult heads specimens were carefully dissected in the zygomatic region, with the location of TB as well as its number documented. The hierarchical relationship between the temporal branch and the soft tissue in this region was observed on 64 P45 plastinated slices. 1. TB crosses the ZA as type I (21.8 %), type II (50.0 %,), and type III (28.1 %) twigs. 2. At the level of the superior edge of the ZA, the average distance between the anterior trunk of TB and the anterior part of the auricle is 36.36±6.56 mm, for the posterior trunk is 25.59±5.29 mm. At the level of the inferior edge of the ZA, the average distance between the anterior trunk of TB and the anterior part of the auricle is 25.77±6.19 mm, for the posterior trunk is 19.16±4.71 mm. 3. The average length of ZA is 62.06±5.36 mm. TB crosses the inferior edge of the ZA at an average of 14.67±6.45 mm. TB crosses the superior edge of the ZA at an average of 9.08±4.54 mm. 4. At the level of the ZA, TB passes on the surface of the pericranium while below the SMAS. The TB obliquely crosses the middle 1/3 part of the superior margin of the ZA and the junction of the middle 1/3 part and the posterior 1/3 part of the inferior margin of the ZA below the SMAS while beyond the periosteum. It is suggested that this area should be avoided in clinical operation to avoid the injury of TB.

El objetivo de estudio fue esclarecer el trayecto del ramo temporal del nervio facial (RT) que cruza el arco cigomático (AC). Se disecaron la región cigomática de 18 especímenes de cabezas sin fijar de individuos adultas y se documentó la ubicación del RT y su número de ramos. La relación jerárquica entre el ramo temporal y el tejido blando en esta región se observó en 64 cortes plastinados o P45. 1º El RT cruza el AC como tipo I (21,8 %), tipo II (50,0 %) y tipo III (28,1 %). 2º A nivel del margen superior del AC, la distancia promedio entre el tronco anterior de RT y la parte anterior de la aurícula fue de 36,36±6,56 mm, para el tronco posterior fue de 25,59±5,29 mm. A nivel del margen inferior del AC, la distancia promedio entre el tronco anterior del RT y la parte anterior de la aurícula era de 25,77±6,19 mm, para el tronco posterior era de 19,16±4,71 mm. 3º La longitud media de RT fue de 62,06±5,36 mm. EL RT cruzaba el margen inferior del AC a una distancia media de 14,67±6,45 mm. El RT cruzaba el margen superior del AC a una distancia media de 9,08±4,54 mm. 4º Anivel del AC, el RT pasaba por la superficie del pericráneo mientras se encuentra por debajo del SMAS. El RT cruza oblicuamente el tercio medio del margen superior del AC y la unión del tercio medio y el tercio posterior del margen inferior del AC por debajo del SMAS, más allá del periostio. Se sugiere que esta área debe evitarse en la operación clínica para evitar la lesión de la RT.

Chuanxiong improves angiogenesis via the PI3K/AKT/Ras/MAPK pathway based on network pharmacology and DESI-MSI metabolomics.

Introduction: Chuanxiong, a traditional Chinese medicine, has been proved to treat a variety of cardiovascular and cerebrovascular diseases by promoting angiogenesis. However, the mechanisms of Chuanxiong's pro-angiogenesis is currently unknown. This study aimed to uncover the effect and mechanisms of Chuanxiong promoting angiogenesis in vivo and in vitro. Methods: First, potential targets were predicted by network pharmacology analysis, and PPI network was established and the pathways were enriched. Then, the chorioallantoic membrane test on quails was applied to assess the proangiogenic effects in vivo. As well, to evaluate the effects in vitro, real-time PCR, western blot analysis, the scratch test, and the tube formation experiment were used. Subsequently, the major metabolic pathways were analyzed using non-targeted metabolomics. Results: As a result of network pharmacological analysis, 51 collective targets of Chuanxiong and angiogenesis were identified, which are mainly associated with PI3K/AKT/Ras/MAPK pathway. And the biological verification results showed that Chuanxiong could increase the vessel numbers and vessel area in qCAM models. Meanwhile, Chuanxiong contributed to HUVEC proliferation, tube formation, migration, by encouraging scratch healing rates and boosting tube branch points. In addition, the levels of VEGFR2, MAPK and PI3K were elevated compared to the control group. The western blot analysis also confirmed Chuanxiong could promote an increase in AKT, FOXO1 and Ras. Furtheremore, metabolomic results showed that the proangiogenic effect of Chuanxiong is associated with glycine, serine and threonine metabolism. Discussion: In conclusion, this study clarified that Chuanxiong could promote angiogenesis in vivo and in vitro via regulating PI3K/AKT/Ras/MAPK pathway.

SerpinG1: A Novel Biomarker Associated With Poor Coronary Collateral in Patients With Stable Coronary Disease and Chronic Total Occlusion.

Background This study aimed to explore predictive biomarkers of coronary collateralization in patients with chronic total occlusion. Methods and Results By using a microarray expression profiling program downloaded from the Gene Expression Omnibus database, weighted gene coexpression network analysis was constructed to analyze the relationship between potential modules and coronary collateralization and screen out the hub genes. Then, the hub gene was identified and validated in an independent cohort of patients (including 299 patients with good arteriogenic responders and 223 patients with poor arteriogenic responders). Weighted gene coexpression network analysis showed that SERPING1 in the light-cyan module was the only gene that was highly correlated with both the gene module and the clinical traits. Serum levels of serpinG1 were significantly higher in patients with bad arteriogenic responders than in patients with good arteriogenic responders (472.53±197.16 versus 314.80±208.92 µg/mL; P<0.001) and were negatively associated with the Rentrop score (Spearman r=-0.50; P<0.001). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.77 (95% CI, 0.72-0.81; P<0.001) for serum serpinG1 in prediction of bad arteriogenic responders. After adjusting for traditional cardiovascular risk factors, serum serpinG1 levels (per SD) remained an independent risk factor for bad arteriogenic responders (odds ratio, 2.20 [95% CI, 1.76-2.74]; P<0.001). Conclusions Our findings illustrate that SERPING1 screened by weighted gene coexpression network analysis was associated with poor collateralization in patients with chronic total occlusion.

Microbial gut diversity in four grasshopper species and its correlation with cellulose digestibility.

Grasshoppers are common pests, and their intestinal microbes have coevolved with them. These microorganisms have varied community structures, and they participate in the nutritional absorption and metabolism of grasshoppers. Here, we describe the gut microbiota diversity of four species of grasshoppers, Oxya chinensis, Pararcyptera microptera meridionalis, Gastrimargus marmoratus, and Calliptamus abbreviatus. We constructed a 16S rDNA gene library and analyzed the digestibility of cellulose and hemicellulose in grasshoppers using moss black phenol and anthrone colorimetry. The grasshopper with the highest microbial diversity in the gut among the four species was Oxya chinensis, and there were no significant differences in gut microbial diversity between the two geographic collections of Oxya chinensis. The most dominant phyla of the four grasshopper gut microorganisms were Proteobacteria, Bacteroidetes, and Firmicutes, and the most dominant genus was Enterobacter. The gut microbiota features of the four grasshoppers were correlated with their cellulose and hemicellulose digestibility. There was a significant positive correlation with cellulose digestibility for Pantoea. A significant negative correlation was found with cellulose digestibility for Acinetobacter, Enterococcus, Citrobacter, Serratia. A significant negative correlation was found with hemicellulose digestibility for Pantoea. This study contributes to the understanding of the structural composition of different species of grasshoppers gut microbiota, which may be useful for developing grasshopper digestive tracts as bioreactors for cellulose decomposition, improving the decomposition and utilization of agricultural straw, producing clean biomass energy, and processing biologically derived products.

Isolation and identification of SiCOL5, which is involved in photoperiod response, based on the quantitative trait locus mapping of Setaria italica.

Foxtail millet (Setaria italica) is a versatile grain and fodder crop grown in arid and semi-arid regions. It is an especially important crop for combating malnutrition in certain poverty-stricken areas of the world. Photoperiod sensitivity is a major constraint to the distribution and utilization of foxtail millet germplasm resources. Foxtail millet may be suitable as a model species for studying the photoperiod sensitivity of C4 crops. However, the genetic basis of the photoperiod response of foxtail millet remains poorly studied. To detect the genetic basis of photoperiod sensitivity-related traits, a recombinant inbred line (RIL) population consisting of 313 lines derived from a cross between the spring-sown cultivar "Longgu 3" and the summer-sown cultivar "Canggu 3" was established. The RIL population was genotyped using whole-genome re-sequencing and was phenotyped in four environments. A high-density genetic linkage map was constructed with an average distance between adjacent markers of 0.69 cM. A total of 21 quantitative trait loci (QTLs) were identified by composite interval mapping, and 116 candidate genes were predicted according to gene annotations and variations between parents, among which three genes were considered important candidate genes by the integration and overall consideration of the results from gene annotation, SNP and indel analysis, cis-element analysis, and the expression pattern of different genes in different varieties, which have different photoperiod sensitivities. A putative candidate gene, SiCOL5, was isolated based on QTL mapping analysis. The expression of SiCOL5 was sensitive to photoperiod and was regulated by biological rhythm-related genes. Function analysis suggested that SiCOL5 positively regulated flowering time. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that SiCOL5 was capable of interacting with SiNF-YA1 in the nucleus.

Functional Characterization of Two RNA Methyltransferase Genes METTL3 and METTL14 Uncovers the Roles of m6A in Mediating Adaptation of Plutella xylostella to Host Plants.

N6-methyladenosine (m6A) is one of the major epigenetic modifications in eukaryotes. Although increasing functions of m6A have been identified in insects, its role in Plutella xylostella L. for host plant adaptation remains unclear. In the current study, we show that the m6A content of P. xylostella was relatively low in different developmental stages and tissues, with no significant differences. Two RNA methyltransferase genes, PxMETTL3 (methyltransferase-like 3) and PxMETTL14 (methyltransferase-like 14), were identified and characterized. PxMETTL3 could be transcribed into two transcripts, and PxMETTL14 had only one transcript; both of these genes were highly expressed in egg and adult stages and reproductive tissues. The CRISPR/Cas9-mediated knockout of PxMETTL3 (ΔPxMETTL3-2) or PxMETTL14 (ΔPxMETTL14-14) confirmed their function in m6A installation into RNA. Furthermore, upon transfer from an artificial diet to the host plant, the mutant strains were affected in terms of larval and pupal weight or adult emergence rate, while the wildtype (WT) strain did not exhibit any difference. In addition, the fecundity and egg hatching rate of the WT strain decreased significantly, whereas only the ΔPxMETTL14-14 mutant strain displayed significantly decreased fecundity. There seemed to be a tradeoff between the stress adaptation and reproduction in P. xylostella mediated by m6A modification. During host transfer, the expression of PxMETTL14 was consistent with the change in m6A content, which implied that PxMETTL14 could respond to host plant defense effectively, and may regulate m6A content. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed transcripts with changes in m6A levels revealed that the potential functions of m6A-related genes may be involved in steroid biosynthesis for larval performance and metabolic pathways for adult reproduction. Overall, our work reveals an epigenetic regulation mechanism for the rapid adaptation of P. xylostella to variations in the host environment.

Effects of heavy ions (12C6+) on malignant melanoma B16F10 cells.

Background: This study aimed to investigate the effects of heavy ion (12C6+) irradiation on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) of B16F10 cells. Methods: The B16F10 cells, which is a malignant melanoma cell line widely used in research, irradiated by 12C6+ and X-ray were detected by Hoechst 33342/propidium iodide double staining, Western blot, flow cytometry, and cell scratch tests to evaluate cell proliferation, expression of apoptosis-related proteins, G2/M phase arrest, cell migration, cell invasion and EMT. Results: Compared with the same physical X-ray dose, 12C6+ could effectively inhibit the proliferation of B16F10 cells, inhibit the expression of B-cell lymphoma-2 (Bcl-2) and cellular-myelocytomatosis viral oncogene (c-Myc), and induce the expression of Bax to promote the apoptosis of B16F10 cells. After 12C6+ irradiation, the B16F10 cells exhibited G2/M phase arrest. B16F10 cells were highly sensitive to 12C6+ irradiation. Moreover, compared with X-ray, the 12C6+ irradiation significantly inhibited the migration of B16F10 cells and inhibited extracellular matrix cleavage, induced E-cadherin expression, enhanced cell adhesion, and further inhibited cell invasion, migration, and EMT. Conclusions: The B16F10 cells were highly radiosensitive to 12C6+. Compared with X-ray, B16F10 cells irradiated by 12C6+ significantly reduced the expressions of matrix metalloproteinases to inhibit extracellular matrix cleavage and, thus, effectively inhibit cell invasion and metastasis. However, although the issue of the different therapeutic effects of heavy ion and X-ray radiotherapy on malignant melanoma was investigated and preliminary research results were obtained, several problems must be further studied.

High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery.

BACKGROUND: The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. METHODS: This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. RESULTS: 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. CONCLUSIONS: This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Analysis of Intestinal Microbial Diversity of Four Species of Grasshoppers and Determination of Cellulose Digestibility.

Grasshoppers (Insecta, Orthoptera, Acridoidea) are a large group of agricultural and animal husbandry pests. They have a large food intake with high utilization of plants fibers. However, the composition of the grasshopper gut microbial community, especially the relationship between gut microbial community and cellulose digestibility, remains unclear. In this research, 16S rRNA gene sequences were used to determine the intestinal microbial diversity of Acrida cinerea, Trilophidia annulata, Atractomorpha sinensis and Sphingonotus mongolicus, and Spearman correlation analysis was performed between the intestinal microbes of grasshoppers and the digestibility of cellulose and hemicellulose. The results showed that Proteobacteria was the dominant phylum and Klebsiella was the dominant genus in the guts of the four species of grasshoppers; there was no significant difference in the species composition of the gut microbes of the four species of grasshoppers. Spearman correlation analysis showed that Brevibacterium and Stenotrophomonas were significantly correlated with cellulose digestibility. Brevibacterium, Clavibacter, Microbacterium and Stenotrophomonas were significantly associated with hemicellulose digestibility. Our results confirmed that the gut microbes of grasshoppers were correlated with the digestibility of cellulose and hemicellulose, and indicated that grasshoppers may have the potential to develop into bioreactors, which can be applied to improve straw utilization efficiency in the future.

Synthesis, Crystal Structure and Separation Performance of p-tert-butyl(tetradecyloxy)calix[6]arene.

This work describes the investigation of separation performance of the p-tert-butyl(tetradecyloxy)calix[6]arene (C6A-C10-OH) as stationary phase for gas chromatography (GC) separations. Its structure was characterized by IR, 1H NMR, 13C NMR, MS and single-crystal X-ray diffraction analysis. The C6A-C10-OH column shows good separation capacity for aliphatic, aromatic and cis-/trans- isomers. Especially, it exhibits multiple molecular recognition interactions for the analytes with a wide range of polarity, including dispersion, π-π, H-bonding and dipole-dipole interactions. The present work provides experimental and theoretical basis for the designing of the new calixarene stationary phases in GC analyses.

Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease.

Path planning and smoothing of mobile robot based on improved artificial fish swarm algorithm.

An algorithm that integrates the improved artificial fish swarm algorithm with continuous segmented Bézier curves is proposed, aiming at the path planning and smoothing of mobile robots. On the one hand, to overcome the low accuracy problems, more inflection points and relatively long planning paths in the traditional artificial fish swarm algorithm for path planning, feasible solutions and a range of step sizes are introduced based on Dijkstra's algorithm. To solve the problems of poor convergence and degradation that hinder the algorithm's ability to find the best in the later stage, a dynamic feedback horizon and an adaptive step size are introduced. On the other hand, to ensure that the planned paths are continuous in both orientation and curvature, the Bessel curve theory is introduced to smooth the planned paths. This is demonstrated through a simulation that shows the improved artificial fish swarm algorithm achieving 100% planning accuracy, while ensuring the shortest average path in the same grid environment. Additionally, the smoothed path is continuous in both orientation and curvature, which satisfies the kinematic characteristics of the mobile robot.

Analysis of the etiological characteristics and drug resistance of adult patients with bloodstream infection in a hospital in Hainan, 2018-2020 / 中国热带医学

@#Abstract: Objective　To analyze the etiological characteristics and drug resistance of patients with bloodstream infection (BSI) in the bacterial resistance monitoring network in Hainan Province from 2018 to 2020, so as to provide laboratory data for clinical diagnosis and treatment. Methods　The clinical data of the subjects were collected, and the etiological characteristics of BSI patients and drug resistance of commonly used drugs in clinical treatment were analyzed retrospectively. SPSS 26.0 software was used for statistical analysis. Results　A total of 877 strains were isolated, including Gram-negative bacteria (584 strains, 66.6%), Gram-positive bacteria (239 strains, 27.2%) and fungi (54 strains, 6.2%); male patients (591 cases, 67.4%), female patients (286 cases, 32.6%); inpatients (780 cases, 88.9%), outpatient and emergency patients (97 cases, 11.1%); the main primary diseases of BSI patients were hypertension, cerebral infarction and type 2 diabetes, and the main primary infections were pulmonary infection and urinary system infection. Intensive care unit (25.2%, 221 cases), emergency department (10.9%, 96 cases), oncology department (9.1%, 80 cases), nephrology department (6.8%, 60 cases) and hepatobiliary and pancreatic surgery department (4.3%, 38 cases) had the highest proportion of pathogenic bacteria. Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative Staphylococcus, Viridans group streptococci and Candida albicans were the most frequently isolated pathogens. The detection rates of carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii were 3.4%, 15.2% and 36.4% respectively. The carbapenem-resistant Escherichia coli was not checked out. The detection rates of methicillin resistant Staphylococcus aureus and methicillin resistant coagulase negative Staphylococcus were 18.5% and 79.1% respectively. Conclusions　Gram-negative bacteria are the most common pathogens of BSI, and inpatients are the main source of BSI. Age, underlying diseases and primary infection are the risk factors of BSI. Clinical laboratories should strengthen the etiological monitoring of high-risk patients with BSI, and the resistance analysis of common antibiotics can provide a basis for the rational use of antibiotics in clinical practice.