We proposed an efficient iterative thresholding method for multi-phase image segmentation. The algorithm is based on minimizing piecewise constant Mumford–Shah functional in which the contour length ...(or perimeter) is approximated by a non-local multi-phase energy. The minimization problem is solved by an iterative method. Each iteration consists of computing simple convolutions followed by a thresholding step. The algorithm is easy to implement and has the optimal complexity O(NlogN) per iteration. We also show that the iterative algorithm has the total energy decaying property. We present some numerical results to show the efficiency of our method.
•We propose a new method for minimizing piecewise constant Mumford–Shah functional.•The contour length (or perimeter) is approximated by a non-local multi-phase energy.•The minimization problem is solved by an iterative thresholding method.•The algorithm has the optimal complexity O(NlogN) per iteration and fast convergence.•We prove rigorously the monotone decay of the iterative algorithm.
The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique ...for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generate the first single cell integrated map of chromatin accessibility and transcriptome in early embryos and demonstrate the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states. The ability to obtain these two layers of omics data will help provide more accurate definitions of "single cell state" and enable the deconvolution of regulatory heterogeneity from complex cell populations.
Salmonella, one of the major causes of foodborne infections, can cause bacterial foodborne illness. We investigated the serotype distribution, multidrug resistance (MDR), and β-lactamase resistance ...genes of human Salmonella isolates collected from clinical specimens in Guizhou, China, between 2013 and 2018. A total of 363 Salmonella isolates were collected from clinical specimens at 17 surveillance hospitals. Twenty-four serotypes were identified by sliding agglutination test. S. Enteritidis (33.9%), Salmonella 4,5,12:i:- (24.0%), S. Typhimurium (16.3%), S. London (6.3%), and S. Derby (3.9%) were the top five serotypes. In 2018, the most common serotype changed from S. Enteritidis to S. Typhimurium. Among the 363 Salmonella isolates, 97.5% of isolates were resistant to at least one class of antimicrobial agents. For cephalosporins, ceftriaxone had the highest resistance rate of 10.5%, and cefepime and cefoxitin were 8.0% and 2.2%, respectively. Three hundred and one (82.9%) Salmonella isolates showed MDR. Salmonella 4,5,12:i:- had the highest MDR rate with 94.2%, followed by S. London (91.3%) and S. Typhimurium (88.1%). Multidrug resistance rates of Salmonella isolates in Guizhou from 2013 to 2017 increased from 75.8% to 86.7%. Sixteen isolates (4.4%) showed extensive drug resistance. One hundred thirty-four antimicrobial resistance patterns were found. Two hundred and forty-one (66.4%) isolates carried at least one β-lactamase resistance gene. The blaTEM gene (61.2%) was the most prevalent resistant gene in all Salmonella isolates, followed by the blaCTX-M gene (6.1%) and blaOXA-1 gene (4.1%). Our findings showed that the MDR rate of Salmonella isolates from Guizhou province increased year by year. Therefore, systematic and long-term surveillance on MDR Salmonella isolates from clinical patients should be further strengthened.
This study monitored the presence of SARS-Cov-2 RNA on environmental surfaces in hospital wards housing patients with mild, severe, and convalescent Coronavirus Disease 2019 (COVID-19), respectively. ...From 29 October to 4 December 2021, a total of 787 surface samples were randomly collected from a General Ward, Intensive Care Unit, and Convalescent Ward at a designated hospital for COVID-19 patients in China. All of the samples were used for SARS-Cov-2 detection. Descriptive statistics were generated and differences in the positivity rates between the wards were analyzed using Fisher's exact tests, Yates chi-squared tests, and Pearson's chi-squared tests. During the study period, 787 surface samples were collected, among which, 46 were positive for SARS-Cov-2 RNA (5.8%). The positivity rate of the contaminated area in the Intensive Care Unit was higher than that of the General Ward (23.5% vs. 10.4%, P<0.05). The positivity rate of the semi-contaminated area in the Intensive Care Unit (4.5%) was higher than that of the General Ward (1.5%), but this difference was not statistically significant (P>0.05). In the clean area, only one sample was positive in the Intensive Care Unit (0.5%). None of the samples were positive in the Convalescent Ward. These findings reveal that the SARS-Cov-2 RNA environmental pollution in the Intensive Care Unit was more serious than that in the General Ward, while the pollution in the Convalescent Ward was the lowest. Strict disinfection measures, personal protection, and hand hygiene are necessary to limit the spread of SARS-Cov-2.
Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here, we report on LiCAT-seq, a technique that enables simultaneous ...profiling of chromatin accessibility and gene expression with ultra-low input of cells, and map the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions. Integrative analyses between the two datasets reveals strong association between the establishment of accessible chromatin and embryonic genome activation (EGA), and uncovers transcription factors and endogenous retrovirus (ERVs) specific to EGA. In particular, a large proportion of the early activated genes and ERVs are bound by DUX4 and become accessible as early as the 2- to 4-cell stages. Our results thus offer mechanistic insights into the molecular events inherent to human pre-implantation development.
In plants, sugar transporters are involved not only in long-distance transport, but also in sugar accumulations in sink cells. To identify members of sugar transporter gene families and to analyze ...their function in fruit sugar accumulation, we conducted a phylogenetic analysis of the Malus domestica genome. Expression profiling was performed with shoot tips, mature leaves, and developed fruit of "Gala" apple. Genes for sugar alcohol including 17 sorbitol transporters (SOTs), sucrose, and monosaccharide transporters, plus SWEET genes, were selected as candidates in 31, 9, 50, and 27 loci, respectively, of the genome. The monosaccharide transporter family appears to include five subfamilies (30 MdHTs, 8 MdEDR6s, 5 MdTMTs, 3 MdvGTs, and 4 MdpGLTs). Phylogenetic analysis of the protein sequences indicated that orthologs exist among Malus, Vitis, and Arabidopsis. Investigations of transcripts revealed that 68 candidate transporters are expressed in apple, albeit to different extents. Here, we discuss their possible roles based on the relationship between their levels of expression and sugar concentrations. The high accumulation of fructose in apple fruit is possibly linked to the coordination and cooperation between MdTMT1/2 and MdEDR6. By contrast, these fruits show low MdSWEET4.1 expression and a high flux of fructose produced from sorbitol. Our study provides an exhaustive survey of sugar transporter genes and demonstrates that sugar transporter gene families in M. domestica are comparable to those in other species. Expression profiling of these transporters will likely contribute to improving our understanding of their physiological functions in fruit formation and the development of sweetness properties.
Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common and essential serotype that causes salmonellosis in Guizhou province. This study aimed to investigate the antimicrobial ...resistance (AMR) and molecular genotyping of 79 S. Enteritidis clinical isolates from 2011 to 2016 in Guizhou, China. Antimicrobial resistance and minimum inhibitory concentrations (MICs) of S. Enteritidis clinical isolates were detected by micro broth dilution method against ten classes 16 antimicrobial agents, and molecular genotyping were examined by pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem repeat analysis (MLVA). All (100%) isolates showed resistance to at least one antimicrobial. Resistance to nalidixic acid (98.7%) was the highest, followed by sulfamethoxazole (87.3%) and ampicillin (77.2%). The majority of isolates (92.4%) showed decreased susceptibility to ciprofloxacin. Resistance to the third and fourth-generation cephalosporins was observed. Twenty-six AMR profiles were observed, and the predominant AMR profile was ampicillin-streptomycin-sulfamethoxazole-amoxicillin/clavulanic acid-nalidixic acid. A high burden of multidrug resistance (MDR) (81.0%) was found. Seventy-nine S. Enteritidis isolates were divided into 33 different pulsotypes (PTs), and the most frequent PT was PT18. Twenty-six different MLVA types (MTs) were generated with seven VNTR loci analysis of these isolates. The dominant PTs and MTs were persistent during 2011-2016. S. Enteritidis clinical isolates showed higher genetic diversity using PFGE combined with MLVA grouped into 60 PT-MT genotypes. No correlation was observed between genotypes, AMR profiles and geographic location. These data revealed the characteristics of AMR and molecular genotyping of S. Enteritidis clinical isolates in Guizhou province. These results highlight that strengthening the AMR and molecular genotyping surveillance is essential to prevent and control salmonellosis in Guizhou. PFGE combined with MLVA should be powerful tools for the molecular genotyping of S. Enteritidis isolates.
Salvianolic acid C (SAC) is a major bioactive component of
(Danshen), a Chinese herb for treating ischemic stroke (IS). However, the mechanism by which SAC affects the IS has not yet been evaluated, ...thus a network pharmacology integrated molecular docking strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. A total of 361 potential SAC-related targets were predicted by SwissTargetPrediction and PharmMapper, and a total of 443 IS-related targets were obtained from DisGeNET, DrugBank, OMIM, and Therapeutic Target database (TTD) databases. SAC-related targets were hit by the 60 targets associated with IS. By Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment combined with the protein-protein interaction (PPI) network and cytoHubba plug-ins, nine related signaling pathways (proteoglycans in cancer, pathways in cancer, PI3K-Akt signaling pathway, Focal adhesion, etc.), and 20 hub genes were identified. Consequently, molecular docking indicated that SAC may interact with the nine targets (F2, MMP7, KDR, IGF1, REN, PPARG, PLG, ACE and MMP1). Four of the target proteins (VEGFR2, MMP1, PPARγ and IGF1) were verified using western blot. This study comprehensively analyzed pathways and targets related to the treatment of IS by SAC. The results of western blot also confirmed that the SAC against IS is mainly related to anti-inflammatory and angiogenesis, which provides a reference for us to find and explore the effective anti-IS drugs.
Objective
The objective of the study was to determine the prognosis and risk factors for additional sex combs like 1 (ASXL1) mutations in patients with acute myeloid leukemia (AML) and ...myelodysplastic syndrome (MDS).
Population and Methods
This retrospective study enrolled 219 adult patients with newly diagnosed AML and MDS, who were treated in West China Hospital from October 2018 to January 2022. The primary clinical outcome was evaluated by overall survival (OS) followed up to January 2023. Kaplan–Meier analysis and Cox multivariate regression analysis were performed to identify potential prognostic parameters in patients with ASXL1 mutations (mt).
Results
A total of 34 (15.53%) ASXL1mt were detected, which occurred more frequently in the elderly and MDS cohorts (p < 0.001). Significantly lower blasts% (p < 0.001) and higher frequencies of mutant RUNX1, SRSF2, STAG2, EZH2, and SETBP1 (p < 0.02) were observed in the ASXL1mt cohort. Patients with ASXL1mt manifested with a worse complete remission rate (p = 0.011), and an inferior OS was shown in subgroups with MDS, co‐mutations of RUNX1, SRSF2, or NRAS, as well as mutations in G646W (p < 0.05). Multivariate analysis considering age, diagnosis, co‐mutations, and mutation site confirmed an independently adverse prognosis of mutations in G646W (HR = 4.302, 95% CI: 1.150–16.097) or RUNX1 co‐mutations (HR = 4.620, 95% CI: 1.385–15.414) in the ASXL1mt cohort.
Conclusion
Our study indicated that mutations in G646W or RUNX1 co‐mutations are closely associated with a dismal clinical outcome in patients with AML and MDS harboring ASXL1mt. Considering the poor prognosis and risk factors in patients with ASXL1mt, more available treatments should be pursued.
A retrospective study was conducted to shed light on potential prognostic risk factors in patients with AML and MDS carrying ASXL1 mutations. Significantly, mutations in G646W and RUNX1 co‐mutations were independently associated with inferior survival.
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