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DNA replication in eukaryotes generates DNA supercoiling, which may intertwine (braid) daughter chromatin fibers to form precatenanes, posing topological challenges during chromosome segregation. The mechanisms that limit precatenane formation remain unclear. By making direct torque measurements, we demonstrate that the intrinsic mechanical properties of chromatin play a fundamental role in dictating precatenane formation and regulating chromatin topology. Whereas a single chromatin fiber is torsionally soft, a braided fiber is torsionally stiff, indicating that supercoiling on chromatin substrates is preferentially directed in front of the fork during replication. We further show that topoisomerase II relaxation displays a strong preference for a single chromatin fiber over a braided fiber. These results suggest a synergistic coordination-the mechanical properties of chromatin inherently suppress precatenane formation during replication elongation by driving DNA supercoiling ahead of the fork, where supercoiling is more efficiently removed by topoisomerase II. VIDEO ABSTRACT.
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Cromatina/química , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Torque , Cromatina/metabolismo , Replicación del ADN , ADN Superhelicoidal/química , Células HeLa , Humanos , Pinzas Ópticas , Saccharomyces cerevisiaeRESUMEN
The bacterial Mfd ATPase is increasingly recognized as a general transcription factor that participates in the resolution of transcription conflicts with other processes/roadblocks. This function stems from Mfd's ability to preferentially act on stalled RNA polymerases (RNAPs). However, the mechanism underlying this preference and the subsequent coordination between Mfd and RNAP have remained elusive. Here, using a novel real-time translocase assay, we unexpectedly discovered that Mfd translocates autonomously on DNA. The speed and processivity of Mfd dictate a "release and catch-up" mechanism to efficiently patrol DNA for frequently stalled RNAPs. Furthermore, we showed that Mfd prevents RNAP backtracking or rescues a severely backtracked RNAP, allowing RNAP to overcome stronger obstacles. However, if an obstacle's resistance is excessive, Mfd dissociates the RNAP, clearing the DNA for other processes. These findings demonstrate a remarkably delicate coordination between Mfd and RNAP, allowing efficient targeting and recycling of Mfd and expedient conflict resolution.
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Proteínas Bacterianas/metabolismo , Elongación de la Transcripción Genética , Factores de Transcripción/metabolismo , Proteínas Bacterianas/genética , ADN/genética , ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Escherichia coli/enzimología , Escherichia coli/genética , Factores de Transcripción/genética , Terminación de la Transcripción GenéticaRESUMEN
Vertical migration behaviour, which is integral to marine energy circulation, is a prevalent trait among marine organisms. However, the behaviour of phytoplankton, particularly beyond diel vertical migration (DVM), remain underexplored compared to groups like zooplankton. Through the lens of the harmful alga Heterosigma akashiwo, which exhibits active vertical migrations and unique fluctuating bloom dynamics, this study aimed to explore the ecological intricacies and diverse benefits of phytoplankton vertical migration behaviours. During the bloom period of H. akashiwo, we unexpectedly observed a dense concentration of cells at bottom layer during daytime. This phase coincided with the emergence of cells related to this species' sexual reproduction. Laboratory experiments further showed an elevated frequency of sexual reproduction in the cell populations that migrated to deeper depths compared to those at the surface. This finding implies a connection between dense bottom accumulation (BA) and the life cycle transitions of the species. This BA phase persisted for two days, after which the populations returned to their standard DVM behaviour, providing insight into the unique fluctuating bloom dynamics of H. akashiwo. Our study suggests that phytoplankton vertical migrations are not strictly dictated by DVM, revealing diverse vertical migration behaviours that may contribute to the complexity of harmful algal bloom patterns.
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Floraciones de Algas Nocivas , Fitoplancton , Reproducción , Fitoplancton/fisiología , Fitoplancton/crecimiento & desarrolloRESUMEN
A novel species of the genus Emticicia, designated BHSR1T, was isolated from a water sample that was collected from the Nakdong River, Republic of Korea, and its taxonomic affiliation was studied using a polyphasic approach. This bacterium was Gram-stain-negative, non-motile, aerobic, curved, rod-shaped, and oxidase- and catalase-negative. The bacterium grew optimally at 37 °C, pH 7.5 and 0% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain BHSR1T should be affiliated with the genus Emticicia, with a high similarity to Emticicia fontis KCTC 52248T (98.10%). Phylogenomic analysis also suggested that the strain represents a novel species in the genus Emticicia. The genomic G + C content was 41.9%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization between strain BHSR1T and its closely related relatives in the genus Emticicia were in ranges of 71.1-75.8%, 69.4-77.5% and 18.6-19.9%, respectively. The gene cluster within BHSR1T contained genes encoding enzymes that could be involved in hormone degradation. The major cellular fatty acids (> 10%) were summed feature 3 (comprising C16:1ω6c and/or C16:1ω7c) and iso-C15:0. With regards to the polar lipid profile, phosphatidylethanolamine (PE), two unidentified aminolipids and three unidentified lipids were identified as the major compounds. The major respiratory quinone was menaquinone (MK)-7. Based on its phylogenetic, phenotypic, chemotaxonomic, and genomic features, strain BHSR1T should be considered a novel species in the genus Emticicia of the family Spirosomaceae, for which the name Emticicia fluvialis sp. nov. is proposed. The type strain was considered BHSR1T (= KCTC 92622T = GDMCC 1.3740T).
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Ácidos Grasos , Ríos , Ríos/microbiología , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos/química , República de CoreaRESUMEN
OBJECTIVE: To investigate the effect of platelet-rich plasma (PRP) injection in patients with atrophic rhinitis. METHODS: Prepared PRP was injected into the inferior turbinate bilaterally, and nasal bacterial cultures were conducted. Improvement of symptoms was assessed with the Nasal Obstruction Symptom Evaluation (NOSE) and the Sino-Nasal Outcome Test-22 (SNOT-22). Nasal mucociliary clearance was assessed using the saccharin transit time (STT). RESULTS: In the PRP-injected group (group A), NOSE (throughout the study) and SNOT-22 (1 month after injection) scores were significantly decreased during the study. However, the saline spray group (group B) showed no significant nasal symptom improvement during the study period. In group A, the STT was improved until 3 months after the injection. In contrast, group B showed STT improvement after 2 months that was maintained throughout the study. CONCLUSION: PRP injections can improve nasal symptoms and nasal mucociliary function in patients with atrophic rhinitis.
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Obstrucción Nasal , Plasma Rico en Plaquetas , Rinitis Atrófica , Rinitis , Humanos , Depuración Mucociliar , Obstrucción Nasal/terapia , Rinitis Atrófica/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: It remains unclear whether the use of adjunctive diagnostic screening methods improves the diagnostic efficacies of oral premalignant and cancerous lesions. OBJECTIVE OF REVIEW: We evaluated the diagnostic accuracy of narrow-band imaging used to detect oral cancer and precancerous lesions defined employing different narrow-band imaging criteria. TYPE OF REVIEW: Systematic review and meta-analyses. SEARCH STRATEGY: We searched PubMed, Scopus, the Web of Science, Embase, Google Scholar and the Cochrane Central Register of Controlled Trials to May 2020. EVALUATION METHODS: Three different criteria for oral mucosal vascular changes using narrow-band imaging were compared: class I: well-demarcated brownish areas with thick dark spots and/or winding vessels; class II: intraepithelial papillary capillary looping of grades 2, 3 and 4; and class III: intraepithelial papillary capillary looping of grades 3 and 4. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (ver. 2) tool. We compared narrow-band imaging to conventional white-light imaging. RESULTS: We included 10 prospective or retrospective studies (1374 patients). To detect all dysplastic and cancerous lesions, the class I criteria afforded the optimal specificity and sensitivity; the area under the summary receiver operating characteristic curve was 0.918. To detect highly dysplastic and advanced cancerous lesions, the class III criteria afforded appropriate specificity and sensitivity. The summary receiver operating characteristic curve was 0.905. When using the class III criteria, narrow-band imaging afforded better specificity (0.941 [range 0.920, 0.9572], P < .0001) compared to white-light imaging (0.520 [range 0.409, 0.629]). However, the white-light imaging data were inconsistent and the ranges were broad; narrow-band imaging may be considerably more accurate than white-light imaging when using the class III criteria. CONCLUSION: Narrow-band imaging diagnosed oral premalignant or cancerous lesions much more reliably than white-light imaging.
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Tamizaje Masivo , Neoplasias de la Boca/diagnóstico por imagen , Imagen de Banda Estrecha , Lesiones Precancerosas/diagnóstico por imagen , Diagnóstico Diferencial , HumanosRESUMEN
Cancer immunoediting enriches NANOG expression in tumor cells, resulting in multi-drug resistance and stem-like phenotypes. We previously demonstrated that these NANOG-associated phenotypes are promoted through HDAC1 transcriptional upregulation. In this study, we identified that NANOG also contributes to the stabilization of HDAC1 protein through the AKT signaling pathway. NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, an E3 ligase for HDAC1 protein, and thereby inhibiting the ubiquitin-mediated degradation of HDAC1. Furthermore, AKT inhibition disrupts HDAC1 WT-mediated phenotypes but had no effect on the phenotypes mediated by HDAC1 FM, a mutant that is unable to interact with CHFR. Critically, we applied a catalytic dead mutant, HDAC1-H141A, to uncover that HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype in tumor cells through its catalytic activity. Collectively, our results establish a firm molecular link in immune-edited tumor cells among NANOG, AKT, CHFR, and HDAC1, identifying HDAC1 as a molecular target in controlling NANOGHIGH immune-refractory cancer.
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Proteínas de Ciclo Celular/metabolismo , Histona Desacetilasa 1/metabolismo , Proteína Homeótica Nanog/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias del Cuello Uterino/inmunología , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos/inmunología , Resistencia a Antineoplásicos/inmunología , Femenino , Células HEK293 , Células HeLa , Histona Desacetilasa 1/genética , Humanos , Mutagénesis Sitio-Dirigida , Fenotipo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization. METHODS: The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia. RESULTS: The allergic group exhibited higher total CT scores than the nonallergic group (P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores (P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores (P = 0.001 and 0.001, respectively). CONCLUSIONS: Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression.
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Three-dimensional (3D) bioprinting is a highly effective technique for fabricating cell-loaded constructs in tissue engineering. However, the versatility of fabricating precise and complex cell-loaded hydrogels is limited owing to the poor crosslinking ability of cell-containing hydrogels. Herein, we propose an optic-fiber-assisted bioprinting (OAB) process to efficiently crosslink methacrylated hydrogels. By selecting appropriate processing conditions for the photo-crosslinking technique, we fabricated biofunctional cell-laden structures including methacrylated gelatin (Gelma), collagen, and decellularized extracellular matrix. To apply the method to skeletal muscle regeneration, cell-laden Gelma constructs were processed with a functional nozzle having a topographical cue and an OAB process that could induce a uniaxial alignment of C2C12 and human adipose stem cells (hASCs). Significantly higher degrees of cell alignment and myogenic activities in the cell-laden Gelma structure were observed compared with those in the cell construct that was printed using a conventional crosslinking method. Moreover, an in vivo regenerative potential was observed in volumetric muscle defects in a mouse model. The hASC-laden construct significantly induced greater muscle regeneration than the cell construct without topographical cues. Based on the results, the newly designed bioprinting process can prove to be highly effective in fabricating biofunctional cell-laden constructs for various tissue engineering applications.
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Lead is one of the most toxic substances. However, there are few ratiometric fluorescent probes for sensing Pb2+ in aqueous solution as well as living cells because specific ligands for Pb2+ ions have not been well characterized. Considering the interactions between Pb2+ and peptides, we developed ratiometric fluorescent probes for Pb2+ based on the peptide receptor in two steps. First, we synthesized fluorescent probes (1-3) based on the tetrapeptide receptor (ECEE-NH2) containing hard and soft ligands by conjugation with diverse fluorophores that showed excimer emission when they aggregated. After investigation of fluorescent responses to metal ions, benzothiazolyl-cyanovinylene was evaluated as an appropriate fluorophore for ratiometric detection of Pb2+. Next, we modified the peptide receptor to decrease the number of hard ligands and/or to replace Cys with disulfide bond and methylated Cys for improving selectivity and cell permeability. From this process, we developed two fluorescent probes (3 and 8) among the probes (1-8) that exhibited remarkable ratiometric sensing properties for Pb2+ including high water solubility (≤2% DMF), visible light excitation, high sensitivity, selectivity for Pb2+, low detection limits (<10 nM), and fast response (<6 min). The binding mode study revealed that specific Pb2+-peptide interactions of the probes caused nanosized aggregates in which the fluorophores of the probes came close each other, exhibiting excimer emission. In particular, 8 based on tetrapeptide bearing a disulfide bond and two carboxyl groups with a good permeability successfully quantified intracellular uptake of Pb2+ in live cells through ratiometric fluorescent signals. The ratiometric sensing system based on specific metal-peptide interactions and excimer emission process could provide a valuable tool to quantify Pb2+ in live cells and pure aqueous solutions.
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Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin's predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function.
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ADN-Topoisomerasas de Tipo II , ADN , ADN-Topoisomerasas de Tipo II/metabolismo , Cromatina , ADN-Topoisomerasas de Tipo I/metabolismo , Células Eucariotas/metabolismoRESUMEN
Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress in vivo. While cellular processes constantly create different degrees of torsional stress, how this stress feeds back to control type IIA topoisomerase function remains obscure. Using a suite of single-molecule approaches, we examined the torsional impact on supercoiling relaxation of both naked DNA and chromatin by eukaryotic topoisomerase II (topo II). We observed that topo II was at least ~ 50-fold more processive on plectonemic DNA than previously estimated, capable of relaxing > 6000 turns. We further discovered that topo II could relax supercoiled DNA prior to plectoneme formation, but with a ~100-fold reduction in processivity; strikingly, the relaxation rate in this regime decreased with diminishing torsion in a manner consistent with the capture of transient DNA loops by topo II. Chromatinization preserved the high processivity of the enzyme under high torsional stress. Interestingly, topo II was still highly processive (~ 1000 turns) even under low torsional stress, consistent with the predisposition of chromatin to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function, capable of enhancing function even under low torsional stress.
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Volumetric muscle loss (VML) is associated with a severe loss of muscle tissue that overwhelms the regenerative potential of skeletal muscles. Tissue engineering has shown promise for the treatment of VML injuries, as evidenced by various preclinical trials. The present study describes the fabrication of a cell-laden GelMa muscle construct using an in situ crosslinking (ISC) strategy to improve muscle functionality. To obtain optimal biophysical properties of the muscle construct, two UV exposure sources, UV exposure dose, and wall shear stress were evaluated using C2C12 myoblasts. Additionally, the ISC system showed a significantly higher degree of uniaxial alignment and myogenesis compared to the conventional crosslinking strategy (post-crosslinking). To evaluate the in vivo regenerative potential, muscle constructs laden with human adipose stem cells were used. The VML defect group implanted with the bio-printed muscle construct showed significant restoration of functionality and muscular volume. The data presented in this study suggest that stem cell-based therapies combined with the modified bioprinting process could potentially be effective against VML injuries.
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BACKGROUND: Early diagnosis of vocal cord iatrogenic injury is crucial, as is perioperative vocal cord evaluation. METHODS: Vocal cord mobility detected via transcutaneous laryngeal ultrasonography was compared with that detected via laryngoscopy (the reference). The vocal cord visualization rate of ultrasonography for evaluation of mobility was explored. RESULTS: The diagnostic odds ratio of transcutaneous laryngeal ultrasonography was 303.2212 (95% CI, [86.7944; 1059.3198]). The area under the summary receiver operating characteristic curve was 0.944. The sensitivity, specificity, and negative predictive value were 0.9154 [0.8471; 0.9548], 0.9771 [0.9541; 0.9887], and 0.9915 [0.9868; 0.9946], respectively. The vocal cord visualization of ultrasonography used to evaluate vocal cord mobility was high (0.9572 [0.9091; 0.9804]). CONCLUSIONS: Since transcutaneous laryngeal ultrasonography has the advantage in vocal cord visualization, it can be considered when laryngoscopy is unavailable or patients refuse laryngoscopy. Also, it is diagnostically accurate regardless of the used landmarks, VCP definition, and timing for application.
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Enfermedades de la Laringe , Parálisis de los Pliegues Vocales , Humanos , Enfermedades de la Laringe/etiología , Glándula Tiroides , Tiroidectomía/efectos adversos , Ultrasonografía , Parálisis de los Pliegues Vocales/diagnóstico por imagen , Parálisis de los Pliegues Vocales/etiología , Pliegues Vocales/diagnóstico por imagenRESUMEN
INTRODUCTION: Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive diagnostic screening method improves diagnostic accuracy. OBJECTIVE: This systematic review and meta-analysis was performed to assess the accuracy of chemiluminescence for diagnosis of oral cancer and precancerous lesions. METHODS: Sixteen prospective and retrospective studies from PubMed, Cochrane database, SCOPUS, Web of Science, Embase, and Google Scholar were reviewed. Oral mucosal disorder, as detected by chemiluminescence, was compared with oral mucosal disorder detected by toluidine blue or visual examination. True-positive, true-negative, false-positive, and false-negative rates were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2). RESULTS: Sensitivity, specificity, negative predictive value, and diagnostic odds ratio (DOR) of the use of toluidine blue were 0.832 (95% confidence interval [CI] 0.692-0.917), 0.429 (95% CI 0.217-0.672), 0.747 (95% CI 0.607-0.849), and 4.061 (95% CI 1.528-10.796; I2=9.128%), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.743. Compared with toluidine blue, as used in 12 studies, chemiluminescence had a higher sensitivity (0.831 vs. 0.694); it had a lower specificity (0.415 vs. 0.734), negative predictive value (0.674 vs. 0.729), and DOR (3.891 vs. 7.705). Compared with clinical examination, as used in three studies, chemiluminescence had lower DOR (4.576 vs. 5.499) and area under the curve (0.818 vs. 0.91). CONCLUSION: Although chemiluminescence itself has good sensitivity for diagnostic work-up of oral cancer and precancer, the diagnostic accuracy of chemiluminescence is comparable to or worse than toluidine blue and clinical examination. Diagnostic accuracy was therefore insufficient for reliable use of chemiluminescence alone.
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Enfermedades de la Boca , Neoplasias de la Boca , Detección Precoz del Cáncer/métodos , Humanos , Luminiscencia , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/patología , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Cloruro de TolonioRESUMEN
Immune checkpoint blockade (ICB) therapy has shifted the paradigm for cancer treatment. However, the majority of patients lack effective responses because of the emergence of immune-refractory tumors that disrupt the amplification of antitumor immunity. Therefore, the identification of clinically available targets that restrict antitumor immunity is required to develop potential combination therapies. Here, using transcriptomic data on patients with cancer treated with programmed cell death protein 1 (PD-1) therapy and newly established mouse preclinical anti-PD-1 therapy-refractory models, we identified NANOG as a factor restricting the amplification of the antitumor immunity cycle, thereby contributing to the immune-refractory feature of the tumor microenvironment (TME). Mechanistically, NANOG induced insufficient T cell infiltration and resistance to CTL-mediated killing via the histone deacetylase 1-dependent (HDAC1-dependent) regulation of CXCL10 and MCL1, respectively. Importantly, HDAC1 inhibition using an actionable agent sensitized NANOGhi immune-refractory tumors to PD-1 blockade by reinvigorating the antitumor immunity cycle. Thus, our findings implicate the NANOG/HDAC1 axis as a central molecular target for controlling immune-refractory tumors and provide a rationale for combining HDAC inhibitors to reverse the refractoriness of tumors to ICB therapy.
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Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Animales , Línea Celular Tumoral , Histona Desacetilasa 1/genética , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Inmunoterapia , Ratones , Proteína Homeótica Nanog/metabolismo , Proteína Homeótica Nanog/farmacología , Receptor de Muerte Celular Programada 1/genéticaRESUMEN
BACKGROUND: As the number of endoscopic skull base surgeries has increased, postoperative changes in quality of life require attention, including evaluation of whether snoring symptoms change. OBJECTIVE: To investigate the effect of endoscopic endonasal skull base surgery on snoring and nasal symptom scores. METHODS: Between February 2009 and September 2018, 510 patients underwent skull base tumor resection via an endoscopic endonasal approach and were included in this study. Nasal symptoms were scored using the Nasal Obstruction Symptoms Evaluation (NOSE) scale and snoring symptoms were subjectively scored from 0 to 10 by partners using a visual analog scale (VAS). Computational fluid dynamics (CFD) was employed for pilot patient analysis. RESULTS: A pituitary adenoma was the most common surgical pathology encountered over the past 10 years (81.6% of all tumors). The NOSE scores increased significantly after surgery (pre-surgery, 3.28 ± 3.18; post-surgery, 4.09 ± 3.61; P < .001). The snoring VAS score decreased significantly postoperatively (pre-surgery, 2.91 ± 2.74; post-surgery, 2.43 ± 2.45; P < .001). A positive correlation was apparent between the NOSE and snoring score changes (r = 0.374; P < .001). CONCLUSIONS: Snoring improved after endoscopic endonasal skull base surgery, associated with changes in nasal symptoms. LEVEL OF EVIDENCE: 4.
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Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.
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Human and animal feces are important sources of various types of microbial contamination in water. Especially, enteric viruses, the major agents of waterborne infection, can attain long-term survival in water environments due to their strong resistance to various environmental factors including pH, salinity, and temperature. Coliphages are promising viral indicators for fecal contamination in water environments. Here, we investigated the seasonal and spatial distribution of male-specific and somatic coliphages in surface water and seawater at three major aquaculture areas, including Goseong Bay, Aphae Island, and Gomso Bay, in Republic of Korea over a period of 1 year. We selected 6 surface water and 14 seawater sampling sites for each study area and collected a total of 480 water samples from March 2014 to February 2015. Overall, surface water samples contained higher occurrences of coliphages than seawater samples. The high coliphage concentrations were detected in spring (March to May 2014). The differences in geographical features and patterns in land usage of the three aquaculture areas may have affected the coliphage concentration and occurrence. Moreover, environmental factors such as cumulative precipitation were strongly correlated with coliphage concentrations. Therefore, we suggest that further longitudinal studies on coliphage concentrations and distributions should be performed to support the application of coliphages in tracking fecal contamination in water.