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62 result(s) for "Hu, Yunjia"
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Characterization and complete genome sequence analysis of a newly isolatedphage against Vibrio parahaemolyticus from sick shrimp in Qingdao, China
Foodborne diseases have become a serious havoc, where antimicrobial resistance is throwing significant challenges on daily basis. With the increase of drug-resistant bacteria and food-borne infection associated with Vibrio parahaemolyticus , new and effective strategies were needed to control the emergence of vibriosis. Lytic bacteriophages come up as a promising way to resist the pathogenic population in various applications. In this study, a V . parahaemolyticus specific phage vB_VpS_PG28 was isolated from sewage in the seafood market. Results showed vB_VpS_PG28, is strictly a lytic bacteriophage and has a relatively large burst size of 103 plaque-forming units per infected cell. Comparative genomic and bioinformatic analyses proved that vB_VpS_PG28 is a new bacteriophage that had a homologous relation with Vibrio phages of family Siphoviridae, especially with phage VH2_2019, but transmission electron microscopy of vB_VpS_PG28 morphology characterized its morphology is similar to that of Myoviridae family. In silico analysis indicated that the vB_VpS_PG28 genome consists of 82712 bp (48.08% GC content) encoding 114 putative ORFs without tRNA,and any gene associated with resistance or virulence factors has not been found. The bacteriophage in the present study has shown significant outcomes in order to control bacterial growth under in vitro conditions. Thus, we are suggesting a beneficiary agent against foodborne pathogens. Further, to ensure the safe usage of phage oral toxicity testing is recommended.
Cell type resolved MR based on brain single cell eQTLs corroborated by single cell RNA sequencing uncovers neuroimmune and vascular programs in intracerebral hemorrhage
Background Intracerebral hemorrhage (ICH) lacks effective neuroprotective therapies. We integrated cell type–resolved genetic inference with single-cell profiling to map putative causal programs and multicellular circuitry relevant to ICH. Methods Cis-eQTLs from eight human brain cell types were used as instruments for two-sample Mendelian randomization (MR), with an ICH meta-analysis from large biobanks and a stroke consortium as the outcome. Instruments were LD-pruned and restricted to strong variants (F > 10). Inverse-variance weighting (IVW) was the primary estimator, supported by robustness methods, heterogeneity/pleiotropy diagnostics, and false discovery rate control. Experimental validation used mouse collagenase ICH single-cell RNA-seq at 24 h ( n  = 3 sham; n  = 3 ICH) with Seurat integration, composition testing, Slingshot pseudotime, and CellChat. An independent mouse cohort underwent qRT–PCR for selected genes. Results The ICH meta-analysis showed acceptable genomic control, supporting downstream MR. We identified 524 nominal gene–cell type associations, with a glia-weighted signal landscape. Enrichment implicated autophagy/mitophagy, antigen processing, cytoskeletal and vesicular trafficking, endothelial matrix–adhesion programs, ferroptosis, and myelin stress pathways. In mouse scRNA-seq, disease-associated microglia expanded with reciprocal loss of homeostatic microglia and increased neutrophils and T cells. Prioritized genes showed directional concordance; qRT–PCR confirmed ARPC3 and EIF2AK2 upregulation and TBCK and SPECC1 downregulation in ICH versus sham. Pseudotime supported a shift toward disease-associated microglial states, and CellChat indicated increased network interaction strength with microglia and endothelium as hubs. Conclusions Cell type–specific MR combined with single-cell validation highlights neuroimmune and neurovascular programs in ICH and links genetic signals to state transitions and inferred intercellular communication.
Artemether, Artesunate, Arteannuin B, Echinatin, Licochalcone B and Andrographolide Effectively Inhibit SARS-CoV-2 and Related Viruses In Vitro
Since the first reported case caused by the novel coronavirus SARS-CoV-2 infection in Wuhan, COVID-19 has caused serious deaths and an ongoing global pandemic, and it is still raging in more than 200 countries and regions around the world and many new variants have appeared in the process of continuous transmission. In the early stage of the epidemic prevention and control and clinical treatment, traditional Chinese medicine played a huge role in China. Here, we screened out six monomer compounds, including artemether, artesunate, arteannuin B, echinatin, licochalcone B and andrographolide, with excellent anti-SARS-CoV-2 and anti-GX_P2V activity from Anti-COVID-19 Traditional Chinese Medicine Compound Library containing 389 monomer compounds extracted from traditional Chinese medicine prescriptions “three formulas and three drugs”. Our discovery preliminary proved the stage of action of those compounds against SARS-CoV-2 and provided inspiration for further research and clinical applications.
Characterization and genome sequence of the genetically unique Escherichia bacteriophage vB_EcoM_IME392
In this study, a novel Escherichia coli-specific bacteriophage, vB_EcoM_IME392, was isolated from chicken farm sewage in Qingdao, China. The genome of IME392 was found by next-generation sequencing to be 116,460 base pairs in length with a G+C content of 45.4% (GenBank accession number MH719082). BLASTn results revealed that only 2% of the genome sequence of IME392 shows sequence similarity to known phage sequences in the GenBank database, which indicates that IME392 is a novel bacteriophage. Transmission electron microscopy showed that IME392 belongs to the family Myoviridae. The host range, the multiplicity of infection, and a one-step growth curve were also determined.
Biological characteristics and genomic analysis of a Stenotrophomonas maltophilia phage vB_SmaS_BUCT548
Stenotrophomonas maltophilia (hereinafter referred to as S. maltophilia) has developed into an important opportunistic pathogenic bacterium, which is prevalent in nosocomial and community infections, and has adverse effects on patients with a compromised immune system. Phage vB_SmaS_BUCT548 was isolated from sewage of Beijing 307 Hospital with S. maltophilia (strain No.824) as a host. Phage morphology was observed by transmission electron microscopy and its biological and genomic characteristics were determined. The electron microscope shows that the bacteriophage belonged to the Siphoviridae and MOI is 0.001. One-step growth curve shows that the incubation period is 30 min and the burst size is 134 PFU/Cell. The host range is relatively wide and it can lysis 11of 13 S. maltophilia strains. Next-Generation Sequencing (NGS) results show that the genome sequence is a dsDNA with 62354 bp length, and the GC content is 56.3% (GenBank: MN937349). One hundred and two online reading frames (ORFs) are obtained after RAST online annotation and the BlastN nucleic acid comparison shows that the phage had low homology with other phages in NCBI database. This study reports a novel S. maltophilia phage named vB_SmaS_BUCT548, which has a short incubation period, strong lytic ability, and a wide host range. The main characteristic of this bacteriophage is the novelty of the genomic sequence and the analysis of the other characteristics provides basic data for further exploring the interaction mechanism between the phage and the host.
USP14-mediated stabilization of ACTN1 maintains mesenchymal characteristics in glioblastoma
Glioblastoma (GBM) is a highly aggressive primary brain tumor with a dismal prognosis, particularly in its mesenchymal (MES) subtype, which correlates strongly with poor survival. Despite this, the mechanisms preserving MES identity remain poorly understood. Here, we show that alpha-actinin 1 (ACTN1) is upregulated in MES GBM and drives proneural-to-mesenchymal transition (PMT). Using patient samples and multiple GBM cell lines, we find that ACTN1 overexpression promotes proliferation, invasion, and tumorigenesis, while its silencing diminishes these malignant traits and shifts gene expression away from MES markers. Mechanistically, we identify ubiquitin-specific peptidase 14 (USP14) as a pivotal deubiquitinase (DUB) that stabilizes ACTN1 by removing its ubiquitin chains. Pharmacological inhibition of USP14 with IU1 reduces ACTN1 protein levels, impairs MES-associated phenotypes, and suppresses tumor progression in vitro and in intracranial xenograft models. Clinically, elevated USP14 and ACTN1 expression correlates with poorer survival in GBM patients, highlighting the USP14–ACTN1 axis as a key driver of PMT and a promising therapeutic target for this devastating disease. USP14 deubiquitinates and stabilizes ACTN1 to sustain the mesenchymal state of glioblastoma and drive tumor growth; clinically, elevated USP14/ACTN1 predicts poorer survival.
Nonlinear piezoresistive effect of 4H–SiC for applications of high temperature pressure sensors
4H–SiC is an ideal material for micro-electromechanical system sensors used in high temperature environment due to its outstanding material properties. In this work, we systematically studied the piezoresistive characteristics of 4H–SiC with different doping concentrations in the range of 25–600 °C. We found that the piezoresistive curves of 4H–SiC with different doping concentrations show clear nonlinear fluctuations ranging from 494 to 600 °C. Moreover, as the doping concentration increases, the critical temperature point of the fluctuations gradually shifts towards higher temperature. Based on the analysis of the charge carrier transport mechanism, we found that the intrinsic excitation of 4H–SiC at high temperature can lead to nonlinear fluctuations in the piezoresistive effect, and proposed a theoretical model of piezoresistive coefficient GF of 4H–SiC under intrinsic excitation. Furthermore, the results of the variable temperature Hall effect test show that increasing the doping concentration of 4H–SiC can effectively suppress the nonlinear piezoresistive effect caused by intrinsic excitation. Based on the above investigation, we conclude that the appropriate doping concentration of 4H–SiC should range from 10 18 to 10 19  cm −3 , which provides important reference for the selection and design of 4H–SiC chip parameters. Graphical abstract
Characterization of the novel temperate Staphylococcus haemolyticus phage IME1365_01
The presence of a novel functional prophage, IME1365_01, was predicted from bacterial high-throughput sequencing data and then successfully induced from Staphylococcus haemolyticus by mitomycin C treatment. Transmission electron microscopy showed that phage IME1365_01 has an icosahedral head (43 nm in diameter) and a long tail (172 nm long). This phage possesses a double-stranded DNA genome of 44,875 bp with a G+C content of 35.35%. A total of 63 putative open reading frames (ORFs) were identified in its genome. BLASTn analysis revealed that IME1365_01 is similar to Staphylococcus phage vB_SepS_E72, but with a genome homology coverage of only 26%. The phage genome does not have fixed termini. In ORF24 of phage IME1365_01, a conserved Toll-interleukin-1 receptor domain of the TIR_2 superfamily (accession no. c123749) is located at its N-terminus, and this might serve as a component of an anti-bacterial system. In conclusion, we developed a platform to obtain active temperate phage from prediction, identification, and induction from its bacterial host. After mass screening using this platform, numerous temperate phages and their innate anti-bacterial elements can provide extensive opportunities for therapy against bacterial (especially drug-resistant bacterial) infections.
Machine learning and deep learning to identifying subarachnoid haemorrhage macrophage‐associated biomarkers by bulk and single‐cell sequencing
We investigated subarachnoid haemorrhage (SAH) macrophage subpopulations and identified relevant key genes for improving diagnostic and therapeutic strategies. SAH rat models were established, and brain tissue samples underwent single‐cell transcriptome sequencing and bulk RNA‐seq. Using single‐cell data, distinct macrophage subpopulations, including a unique SAH subset, were identified. The hdWGCNA method revealed 160 key macrophage‐related genes. Univariate analysis and lasso regression selected 10 genes for constructing a diagnostic model. Machine learning algorithms facilitated model development. Cellular infiltration was assessed using the MCPcounter algorithm, and a heatmap integrated cell abundance and gene expression. A 3 × 3 convolutional neural network created an additional diagnostic model, while molecular docking identified potential drugs. The diagnostic model based on the 10 selected genes achieved excellent performance, with an AUC of 1 in both training and validation datasets. The heatmap, combining cell abundance and gene expression, provided insights into SAH cellular composition. The convolutional neural network model exhibited a sensitivity and specificity of 1 in both datasets. Additionally, CD14, GPNMB, SPP1 and PRDX5 were specifically expressed in SAH‐associated macrophages, highlighting its potential as a therapeutic target. Network pharmacology analysis identified some targeting drugs for SAH treatment. Our study characterised SAH macrophage subpopulations and identified key associated genes. We developed a robust diagnostic model and recognised CD14, GPNMB, SPP1 and PRDX5 as potential therapeutic targets. Further experiments and clinical investigations are needed to validate these findings and explore the clinical implications of targets in SAH treatment.