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MOTIVATION: Unsupervised clustering of single-cell RNA sequencing (scRNA-seq) data holds the promise of characterizing known and novel cell type in various biological and clinical contexts. However, intrinsic multi-scale clustering resolutions poses challenges to deal with multiple sources of variability in the high-dimensional and noisy data. RESULTS: We present ClusterMatch, a stable match optimization model to align scRNA-seq data at the cluster level. In one hand, ClusterMatch leverages the mutual correspondence by canonical correlation analysis (CCA) and multi-scale Louvain clustering algorithms to identify cluster with optimized resolutions. In the other hand it utilizes stable matching framework to align scRNA-seq data in the latent space while maintaining interpretability with overlapped marker gene set. Through extensive experiments, we demonstrate the efficacy of ClusterMatch in data integration, cell type annotation, and cross-species/timepoint alignment scenarios. Our results show ClusterMatch's ability to utilize both global and local information of scRNA-seq data, sets the appropriate resolution of multi-scale clustering, and offers interpretability by utilizing marker genes. AVAILABILITY: The code of CusterMatch software is freely available at https://github.com/AMSSwanglab/ClusterMatch. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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The Alataw Pass, near the Ebinur Lake Wetland (northwest of China) and Taldykorgan (east of Kazakhstan), is a natural habitat for wild rodents. To date, little has been done on the surveillance of Bartonella spp. and Wolbachia spp. from fleas in the region. Here we molecularly detected Bartonella spp. and Wolbachia spp. in wild rodent fleas during January and October of 2016 along the Alataw Pass-Kazakhstan border. A total of 1,706 fleas belonging to 10 species were collected from 6 rodent species. Among the 10 flea species, 4 were found to be positive for Wolbachia, and 5 flea species were positive for Bartonella. Molecular analysis indicated that i) B. rochalimae was firstly identified in Xenopsylla gerbilli minax and X. conforms conforms, ii) B. grahamii was firstly identified in X. gerbilli minax, and iii) B. elizabethae was firstly detected in Coptopsylla lamellifer ardua, Paradoxopsyllus repandus, and Nosopsyllus laeviceps laeviceps. Additionally, 3 Wolbachia endosymbionts were firstly found in X. gerbilli minax, X. conforms conforms, P. repandus, and N. laeviceps laeviceps. BLASTn analysis indicated 3 Bartonella species showed genotypic variation. Phylogenetic analysis revealed 3 Wolbachia endosymbionts were clustered into the non-Siphonaptera Wolbachia group. These findings extend our knowledge of the geographical distribution and carriers of B. rochalimae, B. grahamii, B. elizabethae, and Wolbachia spp. In the future, there is a need for China-Kazakhstan cooperation to strengthen the surveillance of flea-borne pathogens in wildlife.
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Infecções por Bartonella/veterinária , Bartonella/isolamento & purificação , Doenças dos Roedores/microbiologia , Roedores/microbiologia , Sifonápteros/microbiologia , Wolbachia/isolamento & purificação , Animais , Animais Selvagens/microbiologia , Bartonella/classificação , Bartonella/genética , Infecções por Bartonella/microbiologia , China , Genótipo , Cazaquistão , Filogenia , Roedores/classificação , Sifonápteros/classificação , Wolbachia/classificação , Wolbachia/genéticaRESUMO
Subei yak is an essential local yak in the Gansu Province, which genetic resource has recently been discovered. It is a meat-milk dual-purpose variety with high fecundity and relatively stable population genetic structure. However, its population genetic structure and genetic diversity are yet to be reported. Therefore, this study aimed to identify molecular markers of Subei yak genome by whole-genome resequencing, and to analyze the population structure and genetic diversity of Subei yak. This study screened 12,079,496 single nucleotide polymorphism (SNP) molecular markers in the 20 Subei yaks genome using whole-genome resequencing technology. Of these SNPs, 32.09% were located in the intronic region of the genome. Principal component analysis, phylogenetic analysis, and population structure analysis revealed that the Subei yak belonged to an independent group in the domestic yak population. A selective clearance analysis was carried out on Subei yak and other domestic yaks, and the genes under positive selection were annotated. The functional enrichment analysis showed that Subei yak possessed prominent selection characteristics in terms of external environment perception, hypoxia adaptation, and muscle development. Furthermore, Subei yak showed excellent muscle fat deposition and meat quality traits. Thus, this study will serve as a reference for discovering population structure, genetic evolution, and other unique traits of Subei yak and for expanding the genetic variation catalog of yaks.
Subei yak is an important local yak genetic resource newly discovered in Gansu Province. In this study, the molecular markers of Subei yak genome were identified by whole-genome resequencing. Principal component analysis, phylogenetic analysis, and population structure analysis showed that Subei yak belonged to an independent group in the domestic yak population. In addition, functional enrichment analysis showed that Subei yaks had prominent selection characteristics in external environment perception, hypoxia adaptation, and muscle development.
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Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma , Animais , Bovinos/genética , Sequenciamento Completo do Genoma/veterinária , Genoma , Filogenia , Variação Genética , Carne/análiseRESUMO
In this communication, using rice wine residue (RWR) as the support, an edible γ-cyclodextrin-metal-organic framework/RWR (γ-CD-MOF/RWR) composite with a macroscopic morphology was synthesized. The obtained edible composite is promising for applications in drug delivery, adsorption, food processing, and others.
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In the present study, a dark fermentation system inoculated with mixed culture bacteria (MCB) was developed using prepared alkali-based magnetic nanosheets (AMNSs) to facilitate biohydrogen (BioH2) production. The highest BioH2 yields of 232.8 ± 8.5 and 150.3 ± 4.8 mL/g glucose were observed at 100 (mesophilic condition) and 400 (thermophilic condition) mg/L AMNSs groups, which were 65.4% and 43.3%, respectively, above the 0 mg/L AMNSs group. The fermentation pathway revealed that AMNSs enhanced the butyrate-type metabolic pathway and the corresponding nicotinamide adenine dinucleotides (NADHand NAD+) ratio, and hydrogenase activity was enhanced in mesophilic fermentation. The interaction of AMNSs and MCB suggested that AMNSs could assist in electron transfer and that the released metal elements might be responsible for elevated hydrogenase activity. AMNSs also promoted the evolution of the dominant microbial community and altered the content of extracellular polymers, leading to increased production of BioH2.
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Hidrogênio , Microbiota , Álcalis , Fermentação , Fenômenos MagnéticosRESUMO
The occurrence and development of gastric adenocarcinoma (gADC) is closely related to the interaction between tumor cells and immune cells in the tumor microenvironment (TME). Our objective was to characterize the repertoire of immune cells in the TME of gADC. To analyze the transcriptomic, immune, and spatial information of TME in gADC, we constructed single-cell RNA sequencing, 10 × Genomics V(D)J analysis, multiple immunofluorescence techniques, and OSCmap analysis of 49,765 single cells in seven samples from four gADC patients. Our integrative analysis of B cells demonstrated that a large number of mucosal associated lymphoid tissue (MALT)-B cells were detected in the gADC tissues, which have mature tertiary lymphatic structures (mTLSs), and almost no MALT-B cells in peripheral blood sample. Moreover, MALT-B cells are a class of IgA+ plasma cells, which are characterized with high expression of complement pathway activation-related genes. Next, natural killer T (NKT) cells mainly exist in gADC tissues accompanied by mTLSs. This study also classified monocytes/macrophages and epithelial cells into benign and malignant types. Interestingly, CSOmap (q < .05) and multiple immunofluorescence (p < .05) results indicated more types of immune cells can be enriched in tissues with mTLSs than normal TLSs, and the density of mTLSs were higher than normal TLSs. Our findings provide novel insights for the signature of immune cells and tumor cells in the TME of gADC with TLSs and highlight the potential importance of IgA-mediated humoral immunity in gADC patients with TLSs.
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Adenocarcinoma , Neoplasias Gástricas , Estruturas Linfoides Terciárias , Adenocarcinoma/genética , Linfócitos B , Humanos , Neoplasias Gástricas/genética , Estruturas Linfoides Terciárias/genética , Microambiente TumoralRESUMO
Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted. TRIAL REGISTRATION NUMBERS: NCT03423992.
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BACKGROUND: Diabetic macular edema (DME) can cause severe vision impairments for patients with diabetes. Recently, Conbercept has shown efficacy on DME with 3-monthly loading dose injection and pro re nata (PRN, 3+PRN) thereafter in retrospectivetrials. Furthermore, there are some other approaches have been recommended such as 2mg bimonthly (2q8) after 5 initial doses, or Conbercept 0.5mg treat-and-extend, however, some patients still have recurrence of the disease after treatment. Therefore, in order to identify more efficacy and safety approach on Conbercept inpatients with DME, a randomized controlled trial will be performed with 6-monthly loading dose injection and PRN (6+PRN) compared with 3+PRN treatments. METHODS: This study is a multicenter, randomized control trial of Conbecept treating DME in China. Patients with type 2 diabetes suffered from DEM who already planned to receive Conbercept treatment will be recruited. All subjects will be randomized divided into either a study agent treatment group (6+PRN) or a control group (3+PRN), and observes the subjects for 48 weeks after initiation of treatment. RESULTS: This study will provide a new powerful evidence of the efficacy and safety of Conbecept treating DME. DISCUSSION: This RTC study will determine whether multiple treatments of Conbercept provide better effectiveness in patients with DME. TRIAL REGISTRATION NUMBER: ChiCTR2000032728.
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Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Angiografia , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Tomografia de Coerência ÓpticaRESUMO
Based on chest images' features, this paper presents a retrieval method with domination color of partition, gray level co-occurrence matrix and gradient image shape invariant moments, as well as the fusion of them and the technique of relevance feedback. In Windows Vista environment with Visual C + +, a chest image retrieval prototype is implemented and the experiments have proved that this method has a better retrieval effect.
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Algoritmos , Aumento da Imagem , Armazenamento e Recuperação da Informação , Sistemas de Gerenciamento de Base de Dados , Diagnóstico por ImagemRESUMO
BACKGROUND: This study aimed to investigate the effects of antibiotic application on the intestinal flora in elderly hypertension patients with infectious diseases. METHODS: A total of 2350 infected patients treated in Ordos Central Hospital (Inner Mongolia, China) from January 2010 to August 2016 were retrospectively analyzed and 790 healthy hypertension patients were selected as the control group. The 2350 patients were assigned into group A and B based on the administration with narrow-spectrum antibiotic or broad-spectrum antibiotic. The feces specimens of patients at the 1st, 5th, 9th and 14th day after antibiotic treatment were collected to analyze the bacteriological data and the cases of intestinal flora imbalance after applying the narrow-spectrum and broad-spectrum antibiotic were compared and the differences in the bacterial colony compositions of intestinal floras from those of the healthy hypertension patients at the same period were analyzed. RESULTS: The ratio of intestinal flora imbalance was 50.4% after applying antibiotic in patients from group A and 78.3% in group B. grade I and II imbalance were predominant in group A and grade III imbalance was the most severe one in group B (P<0.05). Compared with the intestinal flora in healthy elderly hypertension patients, the ratio of the primary composition flora of patients with imbalanced intestinal flora was changed obviously. CONCLUSION: The application of narrow-spectrum antibiotic and shortening the application time of antibiotic can more effectively protect the normal intestinal flora of elderly hypertension patients.
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Content-based medical image retrieval has become a hot research topic due to the rapid increase of image database. In this paper, we present a method of medical images retrieval, based on texture analysis with Haar wavelet transform. Meanwhile, its effectiveness is compared with the method of retrieval based on co-occurrence matrix. A prototype system is implemented and the experiments show that the method has a much better effect.