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Abstract 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.

Abstract 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.

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.

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.

Background and Objectives Adenotonsillar enlargement is a common cause of pediatric illnesses, including obstructive respiratory disease and recurrent airway infection. The current tonsil grading systems evaluate tonsil size, but the correlation with actual tonsillar size in a clinical setting has not been established. Materials and Method Between May and July of 2018, we recruited 31 children who underwent adenotonsillectomy with no major craniofacial abnormalities. The actual size of the palatine tonsils, the long (L1) and short (S1) axes of the tonsil beyond the anterior pillar, and the real axes (L2 and S2) after tonsil extraction from the fossa were measured during surgery. Adenoid size was determined by measuring the adenoid-nasopharynx (AN) ratio through lateral view x-ray of the neck. Results Though S1 was related to the Friedman scale (p

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.

Abstract 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

Nanog can confer resistance to cancer immunotherapy by promoting AKT activity. Here, the authors demonstrate that HSP90A is a Nanog target that stabilizes the AKT coactivator TCL1, thereby activating AKT, and that HSP90A inhibition can enhance the anti-tumor efficacy of adoptive T cell transfer and checkpoint blockade.

In modern defense technology, signal intelligence plays an important role in military operations as an intelligence source. Among its target signals, telemetry and telecommand signals can use line-coding schemes for their advantageous properties in the presentation of binary data of transmission systems. Therefore, in a non-cooperative context, blind classification of the line-coding scheme is the final crucial step in recovering target information from an unknown received signal. In this paper, we examine the characteristic features of line-coding schemes and then propose a simple blind classification algorithm for the schemes. We also analyze correct classification probabilities of the proposed algorithm in a noiseless and noisy environment through computer simulations. The proposed method can discern line-coding schemes, allowing reconstruction of the original information data.

The main purpose of this study was to investigate the impact of perceived HR practices on affective commitment and turnover intention. This study explored which HR practices were relatively more important in predicting affective commitment and turnover intention. A total of 302 employees from the United States and 317 from South Korea completed the same questionnaires for assessing the aforementioned relationships. The results illustrated that among perceived HR practices, internal mobility had the most significant association with turnover intention in both the United States and South Korea. While internal mobility was a stronger predictor of affective commitment for the United States sample, training was the most important variable for predicting affective commitment in South Korea. The second purpose of the study was to examine whether individuals’ positive affect influences the relationship between perceived HR practices and affective commitment and turnover intention. In the United States, positive affect moderated the relationship between perceived HR practices and affective commitment and turnover intention such that the relationships were stronger for individuals reporting high positive affect relative to those reporting low positive affect. However, these relationships were not significant in South Korea. We discuss the implications of these results, study limitations, and practical suggestions for future research.

A 4+12+16 amplitude phase shift keying (APSK) modulation outperforms other 32-APSK modulations in a nonlinear additive white Gaussian noise (AWGN) channel because of its intrinsic robustness against AM/AM and AM/PM distortions caused by the nonlinear characteristics of a high-power amplifier. Thus, this modulation scheme has been adopted in the digital video broadcasting-satellite2 European standard. And it has been considered for high rate transmission of telemetry data on deep space communications in consultative committee for space data systems which provides a forum for discussion of common problems in the development and operation of space data systems. In this paper, we present an improved bits-to-symbol mapping scheme with a better bit error rate for a 4+12+16 APSK signal in a nonlinear AWGN channel and propose a simple signal detection algorithm for the 4+12+16 APSK from the presented bit mapping.

Rain attenuation can cause a serious problem that an availability of space communication link on Ka band becomes low. To reduce the effect of rain attenuation on the error performance of space communications in Ka band, an adaptive coding and modulation (ACM) scheme is required. In this paper, to achieve a reliable telemetry data transmission, we propose an adaptive coding and modulation level using turbo code recommended by the consultative committee for space data systems (CCSDS) and various modulation methods (QPSK, 8PSK, 4+12 APSK, and 4+12+16 APSK) adopted in the digital video broadcasting-satellite2 (DVB-S2).