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Level Signaling Ligand Jagged1 Enhances Macrophage-Mediated Reply to Helicobacter pylori.
Furthermore, we characterize high-affinity single variable domains on heavy chain (VHH) antibodies that bind to the periplasmic side of HiSiaQM and inhibit sialic acid uptake, providing insight into how TRAP transporter function might be inhibited in vivo.Bacterial topoisomerase I (TopoI) removes excessive negative supercoiling and is thought to relax DNA molecules during transcription, replication and other processes. Using ChIP-Seq, we show that TopoI of Escherichia coli (EcTopoI) is colocalized, genome-wide, with transcribing RNA polymerase (RNAP). Treatment with transcription elongation inhibitor rifampicin leads to EcTopoI relocation to promoter regions, where RNAP also accumulates. When a 14 kDa RNAP-binding EcTopoI C-terminal domain (CTD) is overexpressed, colocalization of EcTopoI and RNAP along the transcription units is reduced. Pull-down experiments directly show that the two enzymes interact in vivo. TPCA-1 nmr Using ChIP-Seq and Topo-Seq, we demonstrate that EcTopoI is enriched upstream (within up to 12-15 kb) of highly-active transcription units, indicating that EcTopoI relaxes negative supercoiling generated by transcription. Uncoupling of the RNAPEcTopoI interaction by either overexpression of EcTopoI competitor (CTD or inactive EcTopoI Y319F mutant) or deletion of EcTopoI domains involved in the interaction is toxic for cells and leads to excessive negative plasmid supercoiling. Moreover, uncoupling of the RNAPEcTopoI interaction leads to R-loops accumulation genome-wide, indicating that this interaction is required for prevention of R-loops formation.Glioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy.Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide. However, effective strategies for cartilage repair are lacking, and patients with advanced OA usually need joint replacement. Better comprehending OA pathogenesis may lead to transformative therapeutics. Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior. Specifically, exosome cargos, such as noncoding RNAs (ncRNAs) and proteins, play a crucial role in OA progression by regulating the proliferation, apoptosis, autophagy, and inflammatory response of joint cells, rendering them promising candidates for OA monitoring and treatment. This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA, suggesting new realms to improve OA management.Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.Bound states in the continuum (BICs) are resonant modes of open structures that do not suffer damping, despite being compatible with radiation in terms of their momentum. They have been raising significant attention for their intriguing topological features, and their opportunities in photonics to enhance light-matter interactions. In parallel, the coherent excitation of optical devices through the tailored interference of multiple beams has been explored as a way to enhance the degree of real-time control over their response. Here, we leverage the combination of these phenomena, and exploit the topological features of BICs in the presence of multiple input beams to enable full polarization control on the entire Poincaré sphere in a photonic crystal slab only supporting a symmetry-protected BIC, experimentally demonstrating highly efficient polarization conversion controlled in real time through the superposition of coherent excitations. Our findings open exciting opportunities for a variety of photonic and quantum optics applications, benefitting from extreme wave interactions and topological features around BICs combined with optical control through coherent interference of multiple excitations.Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for its metastasis remain scarce. We analyzed clinical samples and public database, for differential expression of SLC27A2 and further explored its relationship with clinical prognosis. Biochemistry and functional experiments were carried out to study the potential mechanisms of SLC27A2, CDK3, and EMT. SLC27A2 was significantly downregulated in clinical specimens and renal cancer cell lines and predicted poor prognosis. We found that specific upregulation of SLC27A2 could significantly inhibited the proliferation, migration, and invasion of renal cancer cell lines. SLC27A2 could also influence the Epithelial-mesenchymal transition (EMT) signaling pathway, linked to the progression and metastasis of renal cancer. Using whole transcriptome sequencing of SLC27A2, CDK3 was identified as a regulatory SLC27A2 target. In terms of mechanism, SLC27A2 may further inhibit the epithelial-to-mesenchymal transition by negatively regulating CDK3. Our work suggests that functional inhibition of SLC27A2-CDK3-EMT axis may be an attractive therapeutic target for metastasis of ccRCC.Assessing tumour gene fitness in physiologically-relevant model systems is challenging due to biological features of in vivo tumour regeneration, including extreme variations in single cell lineage progeny. Here we develop a reproducible, quantitative approach to pooled genetic perturbation in patient-derived xenografts (PDXs), by encoding single cell output from transplanted CRISPR-transduced cells in combination with a Bayesian hierarchical model. We apply this to 181 PDX transplants from 21 breast cancer patients. We show that uncertainty in fitness estimates depends critically on the number of transplant cell clones and the variability in clone sizes. We use a pathway-directed allelic series to characterize Notch signaling, and quantify TP53 / MDM2 drug-gene conditional fitness in outlier patients. We show that fitness outlier identification can be mirrored by pharmacological perturbation. Overall, we demonstrate that the gene fitness landscape in breast PDXs is dominated by inter-patient differences.The COVID-19 pandemic has caused massive effects on the situation of public mental health. A fast online questionnaire for screening and evaluating mental symptoms is urgent. In this work, we developed a new 19-item self-assessment Fast Screen Questionnaire for Mental Illness Symptoms (FSQ-MIS) to quickly identify mental illness symptoms. The FSQ-MIS was validated on a total of 3828 young adult mental disorder patients and 984 healthy controls. We applied principal component analysis (PCA), receiver operating characteristic (ROC) curve, and general log-linear analysis (GLA) to evaluate the construct and parallel validity. Results demonstrate that the proposed FSQ-MIS shows high test-retest reliability (0.852) and split-half reliability (0.844). Six factors obtained using PCA explained 54.3% of the variance and showed high correlations with other widely used scales. The ROC results (0.716-0.983) revealed high criterion validity of FSQ-MIS. GLA demonstrated the advantage of FSQ-MIS in predicting anxiety and depression prevalence in COVID-19, supporting the efficiency of FSQ-MIS as a tool for research and clinical practice.Hepatocellular carcinoma (HCC) is one of the most serious malignant cancers and has a high fatality rate. However, clinical strategies for the effective treatment of HCC remain lacking. Long non-coding RNAs (lncRNAs) with aberrant expression have been closely correlated with the occurrence and development of HCC. Here we investigated the underlying mechanism of the lncRNA CERS6-AS1 in HCC progression. The expression and prognosis of CERS6-AS1 in HCC patients was explored using The Cancer Genome Atlas. PCR analysis was utilized to measure the expression of CERS6-AS1 in tissues and cell lines. Transwell, wound healing, proliferation and glycolysis assays were conducted to evaluate the function of CERS6-AS1 on HCC cell functions. Bioinformation methods and luciferase assays were used to screen and verify potential target miRNAs and genes. A subcutaneous tumorigenesis model was constructed in nude mice to assess the effect of CERS6-AS1 on tumorigenesis in vivo. CERS6-AS1 was highly expressed in HCC tissues and cell lines.
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