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6 and ALI ≥32.6 groups), and the median OS times were 19.23 and 39.97 months, respectively (p less then 0.01). A multivariable Cox regression model confirmed that ALI and chemotherapy were independent prognostic factors for OS in patients with NSCLC. OS in the high ALI group was better than that in the low ALI group (HR 1.39; 95% CI 1.03-1.89; p = 0.03). Conclusions Patients with a low ALI tend to have lower OS among those with metastatic NSCLC, and the ALI can serve as an effective prognostic factor for NSCLC patients.The interior of the eukaryotic cell nucleus has a crowded and heterogeneous environment packed with chromatin polymers, regulatory proteins, and RNA molecules. Chromatin polymer, assisted by epigenetic modifications, protein and RNA binders, forms multi-scale compartments which help regulate genes in response to cellular signals. Furthermore, chromatin compartments are dynamic and tend to evolve in size and composition in ways that are not fully understood. The latest super-resolution imaging experiments have revealed a much more dynamic and stochastic nature of chromatin compartments than was appreciated before. An emerging mechanism explaining chromatin compartmentalization dynamics is the phase separation of protein and nucleic acids into membraneless liquid condensates. Consequently, concepts and ideas from soft matter and polymer systems have been rapidly entering the lexicon of cell biology. In this respect, the role of computational models is crucial for establishing a rigorous and quantitative foundation for the new concepts and disentangling the complex interplay of forces that contribute to the emergent patterns of chromatin dynamics and organization. Several multi-scale models have emerged to address various aspects of chromatin dynamics, ranging from equilibrium polymer simulations, hybrid non-equilibrium simulations coupling protein binding and chromatin folding, and mesoscopic field-theoretic models. Fedratinib Here, we review these emerging theoretical paradigms and computational models with a particular focus on chromatin's phase separation and liquid-like properties as a basis for nuclear organization and dynamics.Neuropathic pain (NP) is poorly managed, and in-depth mechanisms of gene transcriptome alterations in NP pathogenesis are not yet fully understood. To determine microRNA-related molecular mechanisms of NP and their transcriptional regulation in NP, PubMed, Embase, Web of Science and CINAHL Complete (EBSCO) were searched from inception to April 2021. Commonly dysregulated miRNAs in NP were assessed. The putative targets of these miRNAs were determined using TargetScan, Funrich, Cytoscape and String database. A total of 133 literatures containing miRNA profiles studies and experimentally verify studies were included. Venn analysis, target gene prediction analysis and functional enrichment analysis indicated several miRNAs (miR-200b-3p, miR-96, miR-182, miR-183, miR-30b, miR-155 and miR-145) and their target genes involved in known relevant pathways for NP. Targets on transient receptor potential channels, voltage-gated sodium channels and voltage-gated calcium channels may be harnessed for pain relief. A further delineation of signal processing and modulation in neuronal ensembles is key to achieving therapeutic success in future studies.G•U wobble base pair frequently occurs in RNA structures. The unique chemical, thermodynamic, and structural properties of the G•U pair are widely exploited in RNA biology. In several RNA molecules, the G•U pair plays key roles in folding, ribozyme catalysis, and interactions with proteins. G•U may occur as a single pair or in tandem motifs with different geometries, electrostatics, and thermodynamics, further extending its biological functions. The metal binding affinity, which is essential for RNA folding, catalysis, and other interactions, differs with respect to the tandem motif type due to the different electrostatic potentials of the major grooves. In this work, we present the crystal structure of an RNA 8-mer duplex r[UCGUGCGA]2, providing detailed structural insights into the tandem motif I (5'UG/3'GU) complexed with Ba2+ cation. We compare the electrostatic potential of the presented motif I major groove with previously published structures of tandem motifs I, II (5'GU/3'UG), and III (5'GG/3'UU). A local patch of a strongly negative electrostatic potential in the major groove of the presented structure forms the metal binding site with the contributions of three oxygen atoms from the tandem. These results give us a better understanding of the G•U tandem motif I as a divalent metal binder, a feature essential for RNA functions.Background Plasma Epstein-Barr virus (EBV) DNA load has been widely used for nasopharyngeal carcinoma (NPC) prognostic risk stratification. However, oral EBV DNA load, a non-invasive biomarker that reflects the EBV lytic replication activity, has not been evaluated for its prognostic value in NPC yet. Methods A total number of 1,194 locoregionally advanced NPC (LA-NPC) patients from south China were included from a prospective observational cohort (GARTC) with a median follow-up of 107.3 months. Pretreatment or mid-treatment mouthwashes were collected for EBV DNA detection by quantitative polymerase chain reaction (qPCR). The difference of pre- and mid-treatment oral EBV DNA load was tested by the Wilcoxon signed-rank test. The associations of oral EBV DNA load with overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed using the log-rank test and multivariate Cox regression. Results The high level of the oral EBV DNA load (>2,100 copies/mL) was independently associated with worse OS (HR = 1.45, 95% CI 1.20-1.74, p less then 0.001), PFS (HR = 1.38, 95% CI 1.16-1.65, p less then 0.001), DMFS (HR = 1.66, 95% CI 1.25-2.21, p = 0.001), and LRFS (HR = 1.43, 95% CI 1.05-1.96, p = 0.023). Similar and robust associations between oral EBV DNA load and prognosis were observed for patients in both the pretreatment and mid-treatment stages. The detection rate (71.7 vs. 48.6%, p less then 0.001) and the median load of oral EBV DNA (13,368 vs. 382 copies/mL, p less then 0.001) for patients in the pretreatment stage were significantly higher than those in the mid-treatment stage. The combination of the oral EBV DNA load and TNM staging provided a more precise risk stratification for the LA-NPC patients. Conclusion Oral EBV DNA load was an alternative non-invasive predictor of prognosis and may facilitate risk stratification for the LA-NPC patients.The commensal microbiome is essential for human health and is involved in many processes in the human body, such as the metabolism process and immune system activation. Emerging evidence implies that specific changes in the microbiome participate in the development of various diseases, including diabetes, liver diseases, tumors, and pathogen infections. Thus, intervention on the microbiome is becoming a novel and effective method to treat such diseases. Synthetic biology empowers researchers to create strains with unique and complex functions, making the use of engineered microbes for clinical applications attainable. The aim of this review is to summarize recent advances about the roles of the microbiome in certain diseases and the underlying mechanisms, as well as the use of engineered microbes in the prevention, detection, and treatment of various diseases.Background Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal type of kidney cancer. Although differential expression of cyclin-dependent kinase-like 2 (CDKL2) has been reported to be associated with tumor progression in other cancers, its prognostic value, and potential mechanism in patients with ccRCC still remain unknown. Methods Gene expression analysis was conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and International Cancer Genome Consortium databases. Further, clinicopathologic analysis; Kaplan-Meier survival analysis; weighted gene co-expression network analysis; gene set enrichment analysis; gene ontology enrichment; methylation; and immune infiltration analyses were performed using TCGA-kidney renal clear cell carcinoma profiles. CDKL2 translational levels were analyzed using The Human Protein Atlas database. Results CDKL2 expression was decreased in ccRCC samples retrieved from the four databases. Gender, survival status, histologic grade, clinical stage, TNM classification, and tumor status were closely related to CDKL2 expression. In addition, CDKL2 downregulation was an independent prognostic factor for poor prognosis in multivariate analysis. Enrichment analyses using multiple tests revealed that CDKL2 is not just closely related to immune response but this association is highly correlated as well. Further, we found that CDKL2 expression was significantly correlated with the infiltration levels of T cell CD4 memory resting; monocytes; macrophages M0, M1, and M2; dendritic cells resting; mast cells resting; plasma cells; T cell CD8; and T cell regulatory. Conclusion This is the first report to study the expression of CDKL2 in ccRCC, wherein we suggest that decreased CDKL2 expression is closely correlated with poor prognosis in ccRCC. We consider that CDKL2 is a novel and potential prognostic biomarker associated with immune infiltrates in ccRCC.Objective Surgical approach to low-grade glioma (LGG) involving the posterior insula is challenging, especially in the left hemisphere, with a high risk of sensorimotor, language, or visual deterioration. In this study, a case series of 5 right-handed patients harboring a left posterior insular LGG is reported, by detailing a transcorticosubcortical approach. Method The five surgeries were achieved in awake patients using cortical and axonal electrostimulation mapping. The glioma was removed through the left rolandic and/or parietal opercula, with preservation of the subcortical connectivity. Results The cortical mapping was positive in the five patients, enabling the selection of an optimal transcortical approach, via the anterolateral supramarginal gyrus in four patients and/or via the lateral retrocentral gyrus in three cases (plus through the left superior temporal gyrus in one case). Moreover, the white matter tracts were identified in all cases, i.e., the lateral part of the superior longitudinal fasciculus (five cases), the arcuate fasciculus (four cases), the thalamocortical somatosensory pathways (four cases), the motor pathway (one case), the semantic pathway (three cases), and the optic tract (one case). Complete resection of the LGG was achieved in two patients and near-total resection in three patients. There were no postoperative permanent sensorimotor, language, or visual deficits. Conclusion A transcortical approach through the parietorolandic operculum in awake patients represents safe and effective access to the left posterior insular LGG. Detection and preservation of the functional connectivity using direct electrostimulation of the white matter bundles are needed in this cross-road brain region to prevent otherwise predictable postsurgical impairments.